Journal articles on the topic 'MNTB neurons'
To see the other types of publications on this topic, follow the link: MNTB neurons.
Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles
Consult the top 50 journal articles for your research on the topic 'MNTB neurons.'
Next to every source in the list of references, there is an 'Add to bibliography' button. Press on it, and we will generate automatically the bibliographic reference to the chosen work in the citation style you need: APA, MLA, Harvard, Chicago, Vancouver, etc.
You can also download the full text of the academic publication as pdf and read online its abstract whenever available in the metadata.
Browse journal articles on a wide variety of disciplines and organise your bibliography correctly.
1
Green, Joshua S., and Dan H. Sanes. "Early Appearance of Inhibitory Input to the MNTB Supports Binaural Processing During Development." Journal of Neurophysiology 94, no. 6 (December 2005): 3826–35. http://dx.doi.org/10.1152/jn.00601.2005.
Full textAbstract:
Despite the peripheral and central immaturities that limit auditory processing in juvenile animals, they are able to lateralize sounds using binaural cues. This study explores a central mechanism that may compensate for these limitations during development. Interaural time and level difference processing by neurons in the superior olivary complex depends on synaptic inhibition from the medial nucleus of the trapezoid body (MNTB), a group of inhibitory neurons that is activated by contralateral sound stimuli. In this study, we examined the maturation of coding properties of MNTB neurons and found that they receive an inhibitory influence from the ipsilateral ear that is modified during the course of postnatal development. Single neuron recordings were obtained from the MNTB in juvenile (postnatal day 15–19) and adult gerbils. Approximately 50% of all recorded MNTB neurons were inhibited by ipsilateral sound stimuli, but juvenile neurons displayed a much greater suppression of firing as compared with those in adults. A comparison of the prepotential and postsynaptic action potential indicated that inhibition occurred at the presynaptic level, likely within the cochlear nucleus. A simple linear model of level difference detection by lateral superior olivary neurons that receive input from MNTB suggested that inhibition of the MNTB may expand the response of LSO neurons to physiologically realistic level differences, particularly in juvenile animals, at a time when these cues are reduced.
2
Brew, Helen M., Joshua X. Gittelman, Robert S. Silverstein, Timothy D. Hanks, Vas P. Demas, Linda C. Robinson, Carol A. Robbins, et al. "Seizures and Reduced Life Span in Mice Lacking the Potassium Channel Subunit Kv1.2, but Hypoexcitability and Enlarged Kv1 Currents in Auditory Neurons." Journal of Neurophysiology 98, no. 3 (September 2007): 1501–25. http://dx.doi.org/10.1152/jn.00640.2006.
Full textAbstract:
Genes Kcna1 and Kcna2 code for the voltage-dependent potassium channel subunits Kv1.1 and Kv1.2, which are coexpressed in large axons and commonly present within the same tetramers. Both contribute to the low-voltage–activated potassium current IKv1, which powerfully limits excitability and facilitates temporally precise transmission of information, e.g., in auditory neurons of the medial nucleus of the trapezoid body (MNTB). Kcna1-null mice lacking Kv1.1 exhibited seizure susceptibility and hyperexcitability in axons and MNTB neurons, which also had reduced IKv1. To explore whether a lack of Kv1.2 would cause a similar phenotype, we created and characterized Kcna2-null mice (−/−). The −/− mice exhibited increased seizure susceptibility compared with their +/+ and +/− littermates, as early as P14. The mRNA for Kv1.1 and Kv1.2 increased strongly in +/+ brain stems between P7 and P14, suggesting the increasing importance of these subunits for limiting excitability. Surprisingly, MNTB neurons in brain stem slices from −/− and +/− mice were hypoexcitable despite their Kcna2 deficit, and voltage-clamped −/− MNTB neurons had enlarged IKv1. This contrasts strikingly with the Kcna1-null MNTB phenotype. Toxin block experiments on MNTB neurons suggested Kv1.2 was present in every +/+ Kv1 channel, about 60% of +/− Kv1 channels, and no −/− Kv1 channels. Kv1 channels lacking Kv1.2 activated at abnormally negative potentials, which may explain why MNTB neurons with larger proportions of such channels had larger IKv1. If channel voltage dependence is determined by how many Kv1.2 subunits each contains, neurons might be able to fine-tune their excitability by adjusting the Kv1.1:Kv1.2 balance rather than altering Kv1 channel density.
3
Müller, Jochen, Daniel Reyes-Haro, Tatjyana Pivneva, Christiane Nolte, Roland Schaette, Joachim Lübke, and Helmut Kettenmann. "The principal neurons of the medial nucleus of the trapezoid body and NG2+ glial cells receive coordinated excitatory synaptic input." Journal of General Physiology 134, no. 2 (July 27, 2009): 115–27. http://dx.doi.org/10.1085/jgp.200910194.
Full textAbstract:
Glial cell processes are part of the synaptic structure and sense spillover of transmitter, while some glial cells can even receive direct synaptic input. Here, we report that a defined type of glial cell in the medial nucleus of the trapezoid body (MNTB) receives excitatory glutamatergic synaptic input from the calyx of Held (CoH). This giant glutamatergic terminal forms an axosomatic synapse with a single principal neuron located in the MNTB. The NG2 glia, as postsynaptic principal neurons, establish synapse-like structures with the CoH terminal. In contrast to the principal neurons, which are known to receive excitatory as well as inhibitory inputs, the NG2 glia receive mostly, if not exclusively, α-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid receptor–mediated evoked and spontaneous synaptic input. Simultaneous recordings from neurons and NG2 glia indicate that they partially receive synchronized spontaneous input. This shows that an NG2+ glial cell and a postsynaptic neuron share presynaptic terminals.
4
Weatherstone, Jessica H., Conny Kopp-Scheinpflug, Nadia Pilati, Yuan Wang, Ian D. Forsythe, Edwin W. Rubel, and Bruce L. Tempel. "Maintenance of neuronal size gradient in MNTB requires sound-evoked activity." Journal of Neurophysiology 117, no. 2 (February 1, 2017): 756–66. http://dx.doi.org/10.1152/jn.00528.2016.
Full textAbstract:
The medial nucleus of the trapezoid body (MNTB) is an important source of inhibition during the computation of sound location. It transmits fast and precisely timed action potentials at high frequencies; this requires an efficient calcium clearance mechanism, in which plasma membrane calcium ATPase 2 (PMCA2) is a key component. Deafwaddler ( dfw 2J) mutant mice have a null mutation in PMCA2 causing deafness in homozygotes ( dfw 2J/ dfw 2J) and high-frequency hearing loss in heterozygotes (+/ dfw 2J). Despite the deafness phenotype, no significant differences in MNTB volume or cell number were observed in dfw 2J homozygous mutants, suggesting that PMCA2 is not required for MNTB neuron survival. The MNTB tonotopic axis encodes high to low sound frequencies across the medial to lateral dimension. We discovered a cell size gradient along this axis: lateral neuronal somata are significantly larger than medially located somata. This size gradient is decreased in +/ dfw 2J and absent in dfw 2J/ dfw 2J. The lack of acoustically driven input suggests that sound-evoked activity is required for maintenance of the cell size gradient. This hypothesis was corroborated by selective elimination of auditory hair cell activity with either hair cell elimination in Pou4f3 DTR mice or inner ear tetrodotoxin (TTX) treatment. The change in soma size was reversible and recovered within 7 days of TTX treatment, suggesting that regulation of the gradient is dependent on synaptic activity and that these changes are plastic rather than permanent. NEW & NOTEWORTHY Neurons of the medial nucleus of the trapezoid body (MNTB) act as fast-spiking inhibitory interneurons within the auditory brain stem. The MNTB is topographically organized, with low sound frequencies encoded laterally and high frequencies medially. We discovered a cell size gradient along this axis: lateral neurons are larger than medial neurons. The absence of this gradient in deaf mice lacking plasma membrane calcium ATPase 2 suggests an activity-dependent, calcium-mediated mechanism that controls neuronal soma size.
5
Kadner, Alexander, Randy J. Kulesza, and Albert S. Berrebi. "Neurons in the Medial Nucleus of the Trapezoid Body and Superior Paraolivary Nucleus of the Rat May Play a Role in Sound Duration Coding." Journal of Neurophysiology 95, no. 3 (March 2006): 1499–508. http://dx.doi.org/10.1152/jn.00902.2005.
Full textAbstract:
We describe neurons in two nuclei of the superior olivary complex that display differential sensitivities to sound duration. Single units in the medial nucleus of the trapezoid body (MNTB) and superior paraolivary nucleus (SPON) of anesthetized rats were studied. MNTB neurons produced primary-like responses to pure tones and displayed a period of suppressed spontaneous activity after stimulus offset. In contrast, neurons of the SPON, which receive a strong glycinergic input from MNTB, showed very little or no spontaneous activity and responded with short bursts of action potentials after the stimulus offset. Because SPON spikes were restricted to the same time window during which suppressed spontaneous activity occurs in the MNTB, we presume that SPON offset activity represents a form of postinhibitory rebound. Using characteristic frequency tones of 2- to 1,000-ms duration presented 20 dB above threshold, we show that the profundity and duration of the suppression of spontaneous activity in MNTB as well as the magnitude and first spike latency of the SPON offset response depend on stimulus duration as well as on stimulus intensity, showing a tradeoff between intensity and duration. Pairwise comparisons of the responses to stimuli of various durations revealed that the duration sensitivity in both nuclei is sharpest for stimuli <50 ms.
6
Leao, Richardson N., Sharon Oleskevich, Hong Sun, Melissa Bautista, Robert E. W. Fyffe, and Bruce Walmsley. "Differences in Glycinergic mIPSCs in the Auditory Brain Stem of Normal and Congenitally Deaf Neonatal Mice." Journal of Neurophysiology 91, no. 2 (February 2004): 1006–12. http://dx.doi.org/10.1152/jn.00771.2003.
Full textAbstract:
We have investigated the fundamental properties of central auditory glycinergic synapses in early postnatal development in normal and congenitally deaf ( dn/dn) mice. Glycinergic miniature inhibitory postsynaptic currents (mIPSCs) were recorded using patch-clamp methods in neurons from a brain slice preparation of the medial nucleus of the trapezoid body (MNTB), at 12-14 days postnatal age. Our results show a number of significant differences between normal and deaf mice. The frequency of mIPSCs is greater (50%) in deaf versus normal mice. Mean mIPSC amplitude is smaller in deaf mice than in normal mice (mean mIPSC amplitude: deaf, 64 pA; normal, 106 pA). Peak-scaled fluctuation analysis of mIPSCs showed that mean single channel conductance is greater in the deaf mice (deaf, 64 pS; normal, 45 pS). The mean decay time course of mIPSCs is slower in MNTB neurons from deaf mice (mean half-width: deaf, 2.9 ms; normal, 2.3 ms). Light- and electron-microscopic immunolabeling results showed that MNTB neurons from deaf mice have more (30%) inhibitory synaptic sites (postsynaptic gephyrin clusters) than MNTB neurons in normal mice. Our results demonstrate substantial differences in glycinergic transmission in normal and congenitally deaf mice, supporting a role for activity during development in regulating both synaptic structure (connectivity) and the fundamental (quantal) properties of mIPSCs at central glycinergic synapses.
7
Mayer, Florian, Otto Albrecht, Anna Dondzillo, and Achim Klug. "Glycinergic inhibition to the medial nucleus of the trapezoid body shows prominent facilitation and can sustain high levels of ongoing activity." Journal of Neurophysiology 112, no. 11 (December 1, 2014): 2901–15. http://dx.doi.org/10.1152/jn.00864.2013.
Full textAbstract:
Neurons in the medial nucleus of the trapezoid body (MNTB) are well known for their prominent excitatory inputs, mediated by the calyx of Held. Less attention has been paid to the prominent inhibitory inputs that MNTB neurons also receive. Because of their auditory nature, both excitatory and inhibitory synapses are highly active in vivo. These high levels of activity are known to reduce excitatory synaptic currents considerably, such that in vivo synaptic currents produced by the calyx are smaller than typically measured in standard brain slice experiments. The goal of this study was to investigate the properties of the inhibitory inputs in the Mongolian gerbil ( Meriones unguiculatus) under activity levels that correspond to those in the intact brain to facilitate a direct comparison between the two inputs. Our results suggest that inhibitory inputs to MNTB are largely mediated by a fast and phasic glycinergic component, and to a lesser degree by a GABAergic component. The glycinergic component can sustain prolonged high levels of activity. Even when challenged with stimulus patterns consisting of thousands of stimuli over tens of minutes, glycinergic inputs to MNTB maintain large conductances and fast decays and even facilitate substantially when the stimulation frequency is increased. The inhibition is mediated by a relatively small number of independent input fibers. The data presented here suggest that inhibitory inputs to MNTB sustain high levels of activity and need to be considered for a full understanding of mechanisms underlying processing of auditory information in MNTB.
8
Wu, S. H., and J. B. Kelly. "Physiological properties of neurons in the mouse superior olive: membrane characteristics and postsynaptic responses studied in vitro." Journal of Neurophysiology 65, no. 2 (February 1, 1991): 230–46. http://dx.doi.org/10.1152/jn.1991.65.2.230.
Full textAbstract:
1. The physiological properties of cells in the superior olivary complex (SOC) were studied in 400-microns brain slices taken through the mouse auditory brain stem. Coronal sections were prepared from fresh brain tissue and were placed fully submerged in an oxygenated saline solution. The boundaries of the medial nucleus of the trapezoid body (MNTB), the lateral superior olive (LSO), and the fibers of the trapezoid body were visualized through a dissecting microscope, and micropipettes filled with 4 M potassium acetate were inserted into the LSO or MNTB. 2. Bipolar stimulating electrodes were placed along the trapezoid body usually at the midline decussation and at a location just lateral to the LSO. This arrangement allowed for stimulation of the trapezoid body both contralateral and ipsilateral to the SOC. Synaptic potentials were elicited by delivering brief (0.1 ms) current pulses to the fibers of the trapezoid body. In some cases the integrity of the fibers was confirmed by transport of horseradish peroxidase (HRP) after extracellular microinjections at various locations along the pathway. The HRP reaction product revealed active transport within the trapezoid body and characteristic synaptic and terminal morphology in the MNTB and LSO. The MNTB contained primarily large-diameter fibers terminating in specialized endings (the calyces of Held), whereas the LSO contained mainly small-diameter fibers and punctate terminal boutons. 3. Membrane characteristics of cells in MNTB and LSO were determined by injecting current into the cell and measuring the corresponding voltage change. Neurons in LSO exhibited a roughly linear relation between voltage and intracellularly injected current. Negative current resulted in a graded hyperpolarization of the cell membrane, and positive current resulted in a graded depolarization that led to the production of action potentials. The number of action potentials was directly related to the strength of the current injected. In contrast, the neurons in MNTB had current-voltage relations that were strongly nonlinear around resting potential. The injection of negative current led to graded hyperpolarization, but injection of positive current produced a limited depolarization that resulted in either a single large action potential or an action potential followed by several spikes with greatly reduced amplitude. 4. Excitatory postsynaptic potentials (EPSPs) could be elicited in LSO by ipsilateral stimulation of the trapezoid body and in MNTB by contralateral stimulation. In response to repeated stimulation, some cells in LSO exhibited temporal summation, that is, a series of slightly subthreshold current pulses produced postsynaptic potentials that combined to elicit action potentials.(ABSTRACT TRUNCATED AT 400 WORDS)
9
Kim, Jun Hee, and Henrique von Gersdorff. "Suppression of spikes during posttetanic hyperpolarization in auditory neurons: the role of temperature, Ih currents, and the Na+-K+-ATPase pump." Journal of Neurophysiology 108, no. 7 (October 1, 2012): 1924–32. http://dx.doi.org/10.1152/jn.00103.2012.
Full textAbstract:
In vivo recordings from postsynaptic neurons in the medial nucleus of the trapezoid body (MNTB), an auditory brain stem nucleus, show that acoustic stimulation produces a burst of spikes followed by a period of hyperpolarization and suppressed spiking activity. The underlying mechanism for this hyperpolarization and reduced spiking is unknown. Furthermore, the mechanisms that control excitability and resting membrane potential are not fully determined for these MNTB neurons. In this study we investigated the excitability of principal neurons from the MNTB after high-frequency afferent fiber stimulation, using whole cell recordings from postnatal day 15–17 rat brain stem slices. We found that Na+-K+-ATPase activity mediates a progressive hyperpolarization during a prolonged tetanic train and a posttetanic hyperpolarization (PTH) at the end of the train, when postsynaptic action potentials failed to fire. Raising the temperature to more physiological levels (from 22 to 35°C) depolarized the resting membrane potential of both presynaptic and postsynaptic cells and decreased the latency of action potential firing during PTH. Higher temperatures also reduced the presynaptic calyx action potential failure rates by 50% during presynaptic PTH, thus increasing the safety-factor for presynaptic spiking. The effect of temperature on hyperpolarization-activated cation current ( Ih) is reflected in the resting potential at both pre- and postsynaptic neurons. We thus propose that temperature-sensitive Na+-K+-ATPase activity and Ih contribute to set the resting membrane potential and produce a brief period of suppressed spiking (or action potential failures) after a prolonged high-frequency afferent tetanus.
10
Walcher, Jan, Benjamin Hassfurth, Benedikt Grothe, and Ursula Koch. "Comparative posthearing development of inhibitory inputs to the lateral superior olive in gerbils and mice." Journal of Neurophysiology 106, no. 3 (September 2011): 1443–53. http://dx.doi.org/10.1152/jn.01087.2010.
Full textAbstract:
Interaural intensity differences are analyzed in neurons of the lateral superior olive (LSO) by integration of an inhibitory input from the medial nucleus of the trapezoid body (MNTB), activated by sound from the contralateral ear, with an excitatory input from the ipsilateral cochlear nucleus. The early postnatal refinement of this inhibitory MNTB-LSO projection along the tonotopic axis of the LSO has been extensively studied. However, little is known to what extent physiological changes at these inputs also occur after the onset of sound-evoked activity. Using whole-cell patch-clamp recordings of LSO neurons in acute brain stem slices, we analyzed the developmental changes of inhibitory synaptic currents evoked by MNTB fiber stimulation occurring after hearing onset. We compared these results in gerbils and mice, two species frequently used in auditory research. Our data show that neither the number of presumed input fibers nor the conductance of single fibers significantly changed after hearing onset. Also the amplitude of miniature inhibitory currents remained constant during this developmental period. In contrast, the kinetics of inhibitory synaptic currents greatly accelerated after hearing onset. We conclude that tonotopic refinement of inhibitory projections to the LSO is largely completed before the onset of hearing, whereas acceleration of synaptic kinetics occurs to a large part after hearing onset and might thus be dependent on proper auditory experience. Surprisingly, inhibitory input characteristics, as well as basic membrane properties of LSO neurons, were rather similar in gerbils and mice.
11
Chang, Daphne, Quetanya Brown, Grace Tsui, Ye He, Jia Liu, Lingyan Shi, and Adrián Rodríguez-Contreras. "Distinct Cellular Profiles of Hif1a and Vegf mRNA Localization in Microglia, Astrocytes and Neurons during a Period of Vascular Maturation in the Auditory Brainstem of Neonate Rats." Brain Sciences 11, no. 7 (July 18, 2021): 944. http://dx.doi.org/10.3390/brainsci11070944.
Full textAbstract:
Defining the relationship between vascular development and the expression of hypoxia-inducible factors (Hifs) and vascular endothelial growth factor (Vegf) in the auditory brainstem is important to understand how tissue hypoxia caused by oxygen shortage contributes to sensory deficits in neonates. In this study, we used histology, molecular labeling, confocal microscopy and 3D image processing methods to test the hypothesis that significant maturation of the vascular bed in the medial nucleus of the trapezoid body (MNTB) occurs during the postnatal period that precedes hearing onset. Isolectin-B4 histochemistry experiments suggested that the MNTB vasculature becomes more elaborate between P5 and P10. When combined with a cell proliferation marker and immunohistochemistry, we found that vascular growth coincides with a switch in the localization of proliferating cells to perivascular locations, and an increase in the density of microglia within the MNTB. Furthermore, microglia were identified as perivascular cells with proliferative activity during the period of vascular maturation. Lastly, combined in situ hybridization and immunohistochemistry experiments showed distinct profiles of Hif1a and Vegf mRNA localization in microglia, astrocytes and MNTB principal neurons. These results suggest that different cells of the neuro-glio-vascular unit are likely targets of hypoxic insult in the auditory brainstem of neonate rats.
12
Wu, S. H., and J. B. Kelly. "Inhibition in the superior olivary complex: pharmacological evidence from mouse brain slice." Journal of Neurophysiology 73, no. 1 (January 1, 1995): 256–69. http://dx.doi.org/10.1152/jn.1995.73.1.256.
Full textAbstract:
1. The effects of gamma-aminobutyric acid (GABA) and glycine and their respective antagonists were determined for neurons in the mouse superior olivary complex. Brain slices (400 microns) were cut in the frontal plane and maintained in an oxygenated saline solution for physiological recording. Recordings were made from neurons in the lateral superior olive (LSO) or medial nucleus of the trapezoid body (MNTB) with glass micropipettes filled with 4 M potassium acetate. 2. Ipsilateral and contralateral synaptic responses were elicited by applying current pulses to the trapezoid body through bipolar stimulating electrodes located at positions lateral and medial to the olivary complex. Both intracellular and extracellular recordings were studied before, during, and after application of drugs to the saline bath containing the tissue slice. 3. Intracellular recordings from 10 neurons in LSO showed that GABA (1-10 mM) caused a concentration-dependent drop in membrane resistance and either reduced or blocked postsynaptic excitatory responses. Similar effects were found in five cells tested with glycine (1-10 mM). Three neurons tested with both GABA and glycine were affected by both drugs. Extracellular spikes were blocked in 53 out of 67 LSO neurons tested with GABA and 29 out of 35 neurons tested with glycine. Seventeen out of 23 neurons tested with both GABA and glycine were affected by both. 4. GABA had a powerful blocking effect on extracellularly recorded action potentials evoked by current-pulse stimulation of the trapezoid body in seven LSO neurons tested after adding the glycine receptor antagonist, strychnine (1 microM), to the bath. GABA also lowered the membrane resistance of one LSO neuron in which intracellular recordings were made in the presence of strychnine. 5. Neurons in MNTB also were affected by GABA and glycine but the proportion of sensitive cells was less than in LSO. GABA reduced membrane resistance in 6 out of 16 neurons and glycine produced a similar effect in 14 out of 26 neurons from which intracellular recordings were made. Six out of 14 neurons tested with GABA and glycine responded to both. Extracellular spikes were eliminated or reduced in amplitude by GABA in 15 out of 44 cells and by glycine in 40 out of 68 cells tested. Eleven out of 29 cells from which extracellular recordings were made were affected by both. 6. The glycine antagonist, strychnine (0.25 - 1.0 muM), blocked both ipsilateral and contralateral inhibitory postsynaptic potentials (IPSPs) in LSO.(ABSTRACT TRUNCATED AT 400 WORDS)
13
Chang, Eric H., Vibhakar C. Kotak, and Dan H. Sanes. "Long-Term Depression of Synaptic Inhibition Is Expressed Postsynaptically in the Developing Auditory System." Journal of Neurophysiology 90, no. 3 (September 2003): 1479–88. http://dx.doi.org/10.1152/jn.00386.2003.
Full textAbstract:
Inhibitory transmission is critically involved in the functional maturation of neural circuits within the brain. However, the mechanisms involved in its plasticity and development remain poorly understood. At an inhibitory synapse of the developing auditory brain stem, we used whole cell recordings to determine the site of induction and expression of long-term depression (LTD), a robust activity-dependent phenomenon that decreases inhibitory synaptic gain and is postulated to underlie synapse elimination. Recordings were obtained from lateral superior olivary (LSO) neurons, and hyperpolarizing inhibitory potentials were evoked by stimulation of the medial nucleus of the trapezoid body (MNTB). Both postsynaptic glycine and GABAA receptors could independently display LTD when isolated pharmacologically. Focal application of GABA, but not glycine, on the postsynaptic LSO neuron was sufficient to induce depression of the amino acid–evoked response, or MNTB-evoked inhibitory postsynaptic potentials. This GABA-mediated depression, in the absence of MNTB stimulation, was blocked by a GABAB receptor antagonist. To assess whether a change in neurotransmitter release is associated with the LTD, the polyvalent cation, ruthenium red, was used to increase the frequency of miniature inhibitory synaptic events. Consistent with a postsynaptic locus of expression, we found that the mean amplitude of miniature events decreased after LTD with no change in their frequency of occurrence. Furthermore, there was no change in the paired-pulse ratio or release kinetics of evoked inhibitory responses. Together, these results provide direct evidence that activity-dependent LTD of inhibition has a postsynaptic locus of induction and alteration, and that GABA but not glycine plays a pivotal role.
14
Brown, Maile R., Lynda El-Hassar, Yalan Zhang, Giuseppe Alvaro, Charles H. Large, and Leonard K. Kaczmarek. "Physiological modulators of Kv3.1 channels adjust firing patterns of auditory brain stem neurons." Journal of Neurophysiology 116, no. 1 (July 1, 2016): 106–21. http://dx.doi.org/10.1152/jn.00174.2016.
Full textAbstract:
Many rapidly firing neurons, including those in the medial nucleus of the trapezoid body (MNTB) in the auditory brain stem, express “high threshold” voltage-gated Kv3.1 potassium channels that activate only at positive potentials and are required for stimuli to generate rapid trains of actions potentials. We now describe the actions of two imidazolidinedione derivatives, AUT1 and AUT2, which modulate Kv3.1 channels. Using Chinese hamster ovary cells stably expressing rat Kv3.1 channels, we found that lower concentrations of these compounds shift the voltage of activation of Kv3.1 currents toward negative potentials, increasing currents evoked by depolarization from typical neuronal resting potentials. Single-channel recordings also showed that AUT1 shifted the open probability of Kv3.1 to more negative potentials. Higher concentrations of AUT2 also shifted inactivation to negative potentials. The effects of lower and higher concentrations could be mimicked in numerical simulations by increasing rates of activation and inactivation respectively, with no change in intrinsic voltage dependence. In brain slice recordings of mouse MNTB neurons, both AUT1 and AUT2 modulated firing rate at high rates of stimulation, a result predicted by numerical simulations. Our results suggest that pharmaceutical modulation of Kv3.1 currents represents a novel avenue for manipulation of neuronal excitability and has the potential for therapeutic benefit in the treatment of hearing disorders.
15
Reyes-Haro, Daniel, Jochen Müller, Margarethe Boresch, Tatjyana Pivneva, Bruno Benedetti, Anja Scheller, Christiane Nolte, and Helmut Kettenmann. "Neuron–astrocyte interactions in the medial nucleus of the trapezoid body." Journal of General Physiology 135, no. 6 (May 17, 2010): 583–94. http://dx.doi.org/10.1085/jgp.200910354.
Full textAbstract:
The calyx of Held (CoH) synapse serves as a model system to analyze basic mechanisms of synaptic transmission. Astrocyte processes are part of the synaptic structure and contact both pre- and postsynaptic membranes. In the medial nucleus of the trapezoid body (MNTB), midline stimulation evoked a current response that was not mediated by glutamate receptors or glutamate uptake, despite the fact that astrocytes express functional receptors and transporters. However, astrocytes showed spontaneous Ca2+ responses and neuronal slow inward currents (nSICs) were recorded in the postsynaptic principal neurons (PPNs) of the MNTB. These currents were correlated with astrocytic Ca2+ activity because dialysis of astrocytes with BAPTA abolished nSICs. Moreover, the frequency of these currents was increased when Ca2+ responses in astrocytes were elicited. NMDA antagonists selectively blocked nSICs while D-serine degradation significantly reduced NMDA-mediated currents. In contrast to previous studies in the hippocampus, these NMDA-mediated currents were rarely synchronized.
16
Kutscher, Andrew, and Ellen Covey. "Functional Role of GABAergic and Glycinergic Inhibition in the Intermediate Nucleus of the Lateral Lemniscus of the Big Brown Bat." Journal of Neurophysiology 101, no. 6 (June 2009): 3135–46. http://dx.doi.org/10.1152/jn.00766.2007.
Full textAbstract:
The intermediate nucleus of the lateral lemniscus (INLL) is a major input to the inferior colliculus (IC), the auditory midbrain center where multiple pathways converge to create neurons selective for specific temporal features of sound. However, little is known about how INLL processes auditory information or how it contributes to integrative processes at the IC. INLL receives excitatory projections from the cochlear nucleus and inhibitory projections from the medial nucleus of the trapezoid body (MNTB), so it must perform some form of integration. To address the question of what role inhibitory synaptic inputs play in the INLL of the big brown bat ( Eptesicus fuscus), we recorded sound-evoked responses of single neurons and iontophoretically applied bicuculline to block GABAA receptors or strychnine to block glycine receptors. Neither bicuculline nor strychnine had a consistent effect on response latency or frequency response areas. Bicuculline increased spike counts and response durations in most units, suggesting that GABAergic input suppressed the late part of the response and provided some gain control. Strychnine reduced the responses of some units with sustained discharge patterns to one or a few spikes at stimulus onset, but increased others. INLL is the only part of the auditory system where reduced responsiveness has been seen in vivo while blocking glycine. However, in vitro studies in the MNTB suggest that glycine can be facilitatory, possibly through presynaptic action. These results show that GABA consistently reduces spike counts and response durations, whereas glycine is suppressive in some INLL neurons but facilitatory in others.
17
Xu, Jie, Emmanuelle Berret, and Jun Hee Kim. "Activity-dependent formation and location of voltage-gated sodium channel clusters at a CNS nerve terminal during postnatal development." Journal of Neurophysiology 117, no. 2 (February 1, 2017): 582–93. http://dx.doi.org/10.1152/jn.00617.2016.
Full textAbstract:
In auditory pathways, the precision of action potential (AP) propagation depends on axon myelination and high densities of voltage-gated Na (Nav) channels clustered at nodes of Ranvier. Changes in Nav channel expression at the heminode, the final node before the nerve terminal, can alter AP invasion into the presynaptic terminal. We studied the activity-dependent formation of Nav channel clusters before and after hearing onset at postnatal day 12 in the rat and mouse auditory brain stem. In rats, the Nav channel cluster at the heminode formed progressively during the second postnatal week, around hearing onset, whereas the Nav channel cluster at the nodes was present before hearing onset. Initiation of heminodal Nav channel clustering was correlated with the expression of scaffolding protein ankyrinG and paranodal protein Caspr. However, in whirler mice with congenital deafness, heminodal Nav channels did not form clusters and maintained broad expression, but Nav channel clustering was normal at the nodes. In addition, a clear difference in the distance from the heminodal Nav channel to the calyx across the mediolateral axis of the medial nucleus of the trapezoid body (MNTB) developed after hearing onset. In the medial MNTB, where neurons respond best to high-frequency sounds, the heminodal Nav channel cluster was located closer to the terminal than in the lateral MNTB, where neurons respond best to low-frequency sounds. Thus sound-mediated neuronal activities are potentially associated with the refinement of the heminode adjacent to the presynaptic terminal in the auditory brain stem. NEW & NOTEWORTHY Clustering of voltage-gated sodium (Nav) channels and their distribution along the axon, specifically at the unmyelinated axon segment next to the nerve terminal, are essential for tuning propagated action potentials. Nav channel clusters near the nerve terminal and their location as a function of neuronal position along the mediolateral axis are controlled by auditory inputs after hearing onset. Thus sound-mediated neuronal activity influences the tonotopic organization of Nav channels at the nerve terminal in the auditory brain stem.
18
Kulesza, Randy J., Alexander Kadner, and Albert S. Berrebi. "Distinct Roles for Glycine and GABA in Shaping the Response Properties of Neurons in the Superior Paraolivary Nucleus of the Rat." Journal of Neurophysiology 97, no. 2 (February 2007): 1610–20. http://dx.doi.org/10.1152/jn.00613.2006.
Full textAbstract:
The superior paraolivary nucleus (SPON) is a prominent periolivary cell group of the superior olivary complex. SPON neurons use γ-aminobutyric acid (GABA) as their neurotransmitter and are contacted by large numbers of glycinergic and GABAergic punctate profiles, representing a dense inhibitory innervation from the medial nucleus of the trapezoid body (MNTB) and from collaterals of SPON axons, respectively. SPON neurons have low rates of spontaneous activity, respond preferentially to the offset of pure tones, and phase-lock to amplitude-modulated tones. To determine the roles of glycine and GABA in shaping SPON responses, we recorded from single units in the SPON of anesthetized rats before, during, and after application of the glycine receptor antagonist strychnine, the GABAA receptor antagonist bicuculline, or both drugs applied simultaneously. Strychnine caused a major increase in spike counts during the stimulus presentation, followed by the disappearance of offset spikes. In half of the recorded units, bicuculline caused moderately increased firing during the stimulus. However, in 86% of units bicuculline also caused a large increase in the magnitude of the offset response. Application of the drug cocktail caused increased spontaneous activity, dramatically increased spike counts during the stimulus presentation, and eliminated the offset response in most units. We conclude that glycinergic inhibition from the MNTB suppresses SPON spiking during sound stimulation and is essential in generating offset responses. GABAergic inhibition, presumably from intrinsic SPON collaterals, plays a subtler role, contributing in some cells to suppression of firing during the stimulus and in most cells to restrict firing after stimulus offset.
19
Kim, Sei Eun, Karl Turkington, Christopher Kushmerick, and Jun Hee Kim. "Central dysmyelination reduces the temporal fidelity of synaptic transmission and the reliability of postsynaptic firing during high-frequency stimulation." Journal of Neurophysiology 110, no. 7 (October 1, 2013): 1621–30. http://dx.doi.org/10.1152/jn.00117.2013.
Full textAbstract:
Auditory brain stem circuits rely on fast, precise, and reliable neurotransmission to process auditory information. To determine the fundamental role of myelination in auditory brain stem function, we examined the evoked auditory brain stem response (ABR) from the Long Evans shaker ( LES) rat, which lacks myelin due to a genetic deletion of myelin basic protein. In control rats, the ABR evoked by a click consisted of five well-defined waves (denoted waves I–V). In LES rats, waves I, IV, and V were present, but waves II and III were undetectable, indicating disrupted function in the earliest stages of central nervous system auditory processing. In addition, the developmental shortening of the interval between waves I and IV that normally occurs in control rats was arrested and resulted in a significant increase in the central conduction time in LES rats. In brain stem slices, action potential transmission between the calyx of Held terminals and the medial nucleus of the trapezoid body (MNTB) neurons was delayed and less reliable in LES rats, although the resting potential, threshold, input resistance, and length of the axon initial segment of the postsynaptic MNTB neurons were normal. The amplitude of glutamatergic excitatory postsynaptic currents (EPSCs) and the degree of synaptic depression during high-frequency stimulation were not different between LES rats and controls, but LES rats exhibited a marked slow component to the EPSC decay and a much higher rate of presynaptic failures. Together, these results indicate that loss of myelin disrupts brain stem auditory processing, increasing central conduction time and reducing the reliability of neurotransmission.
20
Hermann, Joachim, Michael Pecka, Henrique von Gersdorff, Benedikt Grothe, and Achim Klug. "Synaptic Transmission at the Calyx of Held Under In Vivo–Like Activity Levels." Journal of Neurophysiology 98, no. 2 (August 2007): 807–20. http://dx.doi.org/10.1152/jn.00355.2007.
Full textAbstract:
One of the hallmarks of auditory neurons in vivo is spontaneous activity that occurs even in the absence of any sensory stimuli. Sound-evoked bursts of discharges are thus embedded within this background of random firing. The calyx of Held synapse in the medial nucleus of the trapezoid body (MNTB) has been characterized in vitro as a fast relay that reliably fires at high stimulus frequencies (≤800 Hz). However, inherently due to the preparation method, spontaneous activity is absent in studies using brain stem slices. Here we first determine in vivo spontaneous firing rates of MNTB principal cells from Mongolian gerbils and then reintroduce this random firing to in vitro gerbil brain stem synapses at near-physiological temperature. After conditioning synapses with afferent fiber stimulation for 2 min at Poisson averaged rates of 20, 40, and 60 Hz, we observed a number of differences in the properties of synaptic transmission between conditioned and unconditioned synapses. Foremost, we observed reduced steady-state EPSC amplitudes that depressed even further during an embedded short-stimulation train of 100, 300, or 600 Hz (a protocol that thus simulates in vitro what probably occurs at the in vivo MNTB after a short sound stimulus in a silent background). Accordingly, current-clamp, dynamic-clamp, and loose-patch recordings revealed a number of action potential failures at the postsynaptic cell during high-frequency–stimulation trains, although the initial onset of evoked activity was still transmitted with higher fidelity. We thus propose that some in vivo auditory synapses are in a tonic state of reduced EPSC amplitudes as a consequence of high spontaneous spiking and this in vivo–like conditioning has important consequences for the encoding of signals throughout the auditory pathway.
21
Banks, M. I., R. A. Pearce, and P. H. Smith. "Hyperpolarization-activated cation current (Ih) in neurons of the medial nucleus of the trapezoid body: voltage-clamp analysis and enhancement by norepinephrine and cAMP suggest a modulatory mechanism in the auditory brain stem." Journal of Neurophysiology 70, no. 4 (October 1, 1993): 1420–32. http://dx.doi.org/10.1152/jn.1993.70.4.1420.
Full textAbstract:
1. Principal cells in the medial nucleus of the trapezoid body (MNTB) are part of a circuit in the superior olivary complex (SOC) that processes binaural information important for sound localization. MNTB cells have two voltage-dependent currents active near rest that contribute to these cells' highly nonlinear membrane properties and shape their responses to synaptic input. One of these currents, a low-threshold, 4-aminopyridine (4-AP)-sensitive K+ current, has been studied previously under current clamp. Using the single-electrode voltage-clamp technique, we have investigated the other of these currents, a hyperpolarization-activated, mixed cation current (Ih), in brain slices of the rat SOC. 2. Ih is responsible for a prominent "sag" in the voltage response to a steady hyperpolarizing current recorded under current clamp in MNTB cells. In voltage-clamp recordings, hyperpolarizing voltage steps from the resting potential elicited a large inward current that activated and deactivated with biexponential kinetics. Activation time constants were voltage dependent, with tau 1 and tau 2 = 246 and 1620 ms at -75 mV and 107 and 560 ms at -100 mV. 3. Ih was blocked by 1-5 mM cesium and had a reversal potential of -43 mV. Steady-state activation curves derived from tail currents yielded a half-activation voltage of -75.7 mV and slope factor of 5.7 mV, corresponding to < 10% activation of Ih at rest. 4. Application of norepinephrine (15-20 microM) or 8-bromoadenosine 3',5'-cyclic monophosphate (8-Br-cAMP) (1 mM) caused a depolarizing shift in the steady-state activation curve and decreased the activation time constants. The shift in the activation curve resulted in a large increase in the activation of Ih at rest, an inward shift in the holding current, and an increase in the resting membrane conductance. In current-clamp recordings, this increase in the resting activation level of Ih resulted in membrane depolarization of 2-3 mV in the absence of 4-AP, and 5-10 mV in the presence of 4-AP, an increase in the input conductance, and a reduction in the voltage sag in response to hyperpolarizing currents. 5. The resulting change in the resting point of MNTB cells exposed to norepinephrine or 8-Br-cAMP is likely to alter the responses of these cells to synaptic input, both via the direct effect on the resting membrane conductance and by changing the activation of the low-threshold, 4-AP-sensitive potassium current.(ABSTRACT TRUNCATED AT 400 WORDS)
22
Leão, Ricardo M., and Henrique Von Gersdorff. "Noradrenaline Increases High-Frequency Firing at the Calyx of Held Synapse During Development by Inhibiting Glutamate Release." Journal of Neurophysiology 87, no. 5 (May 1, 2002): 2297–306. http://dx.doi.org/10.1152/jn.2002.87.5.2297.
Full textAbstract:
The mammalian auditory brain stem receives profuse adrenergic innervation, whose function is poorly understood. Here we investigate, during postnatal development, the effect of noradrenaline (NA) at the calyx of Held synapse in the rat medial nucleus of the trapezoid body (MNTB). We observed that NA inhibits the large glutamatergic EPSC, evoked by afferent fiber stimulation, in a dose-dependent manner. The inhibition was maximal (approximately 48%) at the concentration of 2 μM. It was antagonized by yohimbine and mimicked by the α2-adrenergic specific agonist UK14304. Both AMPA and NMDA receptor-mediated EPSCs were inhibited in parallel by NA, suggesting a presynaptic effect. Presynaptic recordings showed that NA inhibits the action potential (AP) generated Ca current by about 20%; however, NA did not significantly affect the presynaptic AP waveform. We thus conclude that the calyx of Held presynaptic terminal expresses α2-adrenergic receptors that inhibit its Ca current and thus glutamate release. Noradrenaline was effective in all cells tested from postnatal days 6 to 7 (P6–P7), and thereafter the number of responsive cells diminished, although half of the P14 cells tested still had EPSCs that were inhibited by NA. By contrast, activation byl-2-amino-5-phosphonovaleric acid-sensitive metabotropic glutamate receptors strongly inhibited the EPSCs of all cells tested from P6 to P14. The effect of NA on postsynaptic action potential firing was dependent on the stimulus frequency. At 10 Hz, NA had no effect on firing probability; however, NA helped MNTB cells fire more action potentials during a 100-Hz train of stimuli, even though it did not increase the steady-state depressed EPSC, because it produced a smaller N-methyl-d-aspartate (NMDA) receptor-activated depolarizing plateau. We therefore suggest that the reduction by NA of the first few EPSCs in a train leads to a smaller NMDA depolarizing plateau and thus to increased firing probability at 100 Hz in young synapses. Surprisingly, the inhibition of glutamate release by NA can thus actually increase the excitability of MNTB neurons during early postnatal development.
23
Inchauspe, Carlota González, Francisco J. Urbano, Mariano N. Di Guilmi, Michel D. Ferrari, Arn M. J. M. van den Maagdenberg, Ian D. Forsythe, and Osvaldo D. Uchitel. "Presynaptic CaV2.1 calcium channels carrying familial hemiplegic migraine mutation R192Q allow faster recovery from synaptic depression in mouse calyx of Held." Journal of Neurophysiology 108, no. 11 (December 1, 2012): 2967–76. http://dx.doi.org/10.1152/jn.01183.2011.
Full textAbstract:
CaV2.1 Ca2+ channels have a dominant and specific role in initiating fast synaptic transmission at central excitatory synapses, through a close association between release sites and calcium sensors. Familial hemiplegic migraine type 1 (FHM-1) is an autosomal-dominant subtype of migraine with aura, caused by missense mutations in the CACNA1A gene that encodes the α1A pore-forming subunit of CaV2.1 channel. We used knock-in (KI) transgenic mice harboring the FHM-1 mutation R192Q to study the consequences of this mutation in neurotransmission at the giant synapse of the auditory system formed by the presynaptic calyx of Held terminal and the postsynaptic neurons of the medial nucleus of the trapezoid body (MNTB). Although synaptic transmission seems unaffected by low-frequency stimulation in physiological Ca2+ concentration, we observed that with low Ca2+ concentrations (<1 mM) excitatory postsynaptic currents (EPSCs) showed increased amplitudes in R192Q KI mice compared with wild type (WT), meaning significant differences in the nonlinear calcium dependence of nerve-evoked transmitter release. In addition, when EPSCs were evoked by broadened presynaptic action potentials (achieved by inhibition of K+ channels) via Cav2.1-triggered exocytosis, R192Q KI mice exhibited further enhancement of EPSC amplitude and charge compared with WT mice. Repetitive stimulation of afferent axons to the MNTB at different frequencies caused short-term depression of EPSCs that recovered significantly faster in R192Q KI mice than in WT mice. Faster recovery in R192Q KI mice was prevented by the calcium chelator EGTA-AM, pointing to enlarged residual calcium as a key factor in accelerating the replenishment of synaptic vesicles.
24
Kaczmarek, Leonard K., Arin Bhattacharjee, Rooma Desai, Li Gan, Ping Song, Christian A. A. von Hehn, Matthew D. Whim, and Bo Yang. "Regulation of the timing of MNTB neurons by short-term and long-term modulation of potassium channels." Hearing Research 206, no. 1-2 (August 2005): 133–45. http://dx.doi.org/10.1016/j.heares.2004.11.023.
Full text
25
Wei, Liting, Shotaro Karino, Eric Verschooten, and Philip X. Joris. "Enhancement of phase-locking in rodents. I. An axonal recording study in gerbil." Journal of Neurophysiology 118, no. 4 (October 1, 2017): 2009–23. http://dx.doi.org/10.1152/jn.00194.2016.
Full textAbstract:
The trapezoid body (TB) contains axons of neurons in the anteroventral cochlear nucleus projecting to monaural and binaural nuclei in the superior olivary complex (SOC). Characterization of these monaural inputs is important for the interpretation of response properties of SOC neurons. In particular, understanding of the sensitivity to interaural time differences (ITDs) in neurons of the medial and lateral superior olive requires knowledge of the temporal firing properties of the monaural excitatory and inhibitory inputs to these neurons. In recent years, studies of ITD sensitivity of SOC neurons have made increasing use of small animal models with good low-frequency hearing, particularly the gerbil. We presented stimuli as used in binaural studies to monaural neurons in the TB and studied their temporal coding. We found that general trends as have been described in the cat are present in gerbil, but with some important differences. Phase-locking to pure tones tends to be higher in TB axons and in neurons of the medial nucleus of the TB (MNTB) than in the auditory nerve for neurons with characteristic frequencies (CFs) below 1 kHz, but this enhancement is quantitatively more modest than in cat. Stronger enhancement is common when TB neurons are stimulated at low frequencies below CF. It is rare for TB neurons in gerbil to entrain to low-frequency stimuli, i.e., to discharge a well-timed spike on every stimulus cycle. Also, complex phase-locking behavior, with multiple modes of increased firing probability per stimulus cycle, is common in response to low frequencies below CF. NEW & NOTEWORTHY Phase-locking is an important property of neurons in the early auditory pathway: it is critical for the sensitivity to time differences between the two ears enabling spatial hearing. Studies in cat have shown an improvement in phase-locking from the peripheral to the central auditory nervous system. We recorded from axons in an output tract of the cochlear nucleus and show that a similar but more limited form of temporal enhancement is present in gerbil.
26
Bergsman, Jeremy B., Pietro De Camilli, and David A. McCormick. "Multiple Large Inputs to Principal Cells in the Mouse Medial Nucleus of the Trapezoid Body." Journal of Neurophysiology 92, no. 1 (July 2004): 545–52. http://dx.doi.org/10.1152/jn.00927.2003.
Full textAbstract:
The calyx of Held is a giant nerve terminal that forms a synapse directly onto the principal cells of the medial nucleus of the trapezoid body (MNTB) in the mammalian auditory brain stem. This central synapse, which is involved in sound localization, has become widely used for studying synaptic transmission. Anatomical studies of this nucleus have indicated that each principal cell is innervated by only one calyx. Here we use previously established electrophysiological criteria of excitatory postsynaptic current amplitude, kinetics, and transmitter type, as well as other characteristics commonly reported for this synapse, to examine the input properties of principal neurons. Our findings indicate that some principal cells receive more than one strong excitatory input. These inputs meet previously established electrophysiological criteria for identification as calyceal nerve terminals. Implications for the execution and analysis of experiments to avoid errors due to such multiple inputs are discussed.
27
Grothe, B. "Interaction of excitation and inhibition in processing of pure tone and amplitude-modulated stimuli in the medial superior olive of the mustached bat." Journal of Neurophysiology 71, no. 2 (February 1, 1994): 706–21. http://dx.doi.org/10.1152/jn.1994.71.2.706.
Full textAbstract:
1. In mammals with good low-frequency hearing, the medial superior olive (MSO) processes interaural time or phase differences that are important cues for sound localization. Its cells receive excitatory projections from both cochlear nuclei and are thought to function as coincidence detectors. The response patterns of MSO neurons in most mammals are predominantly sustained. In contrast, the MSO in the mustached bat is a monaural nucleus containing neurons with phasic discharge patterns. These neurons receive projections from the contralateral anteroventral cochlear nucleus (AVCN) and the ipsilateral medial nucleus of the trapezoid body (MNTB). 2. To further investigate the role of the MSO in the bat, the responses of 252 single units in the MSO to pure tones and sinusoidal amplitude-modulated (SAM) stimuli were recorded. The results confirmed that the MSO in the mustached bat is tonotopically organized, with low frequencies in the dorsal part and high frequencies in the ventral part. The 61-kHz region is overrepresented. Most neurons tested (88%) were monaural and discharged only in response to contralateral stimuli. Their response could not be influenced by stimulation of the ipsilateral ear. 3. Only 11% of all MSO neurons were spontaneously active. In these neurons the spontaneous discharge rate was suppressed during the stimulus presentation. 4. The majority of cells (85%) responded with a phasic discharge pattern. About one-half (51%) responded with a level-independent phasic ON response. Other phasic response patterns included phasic OFF or phasic ON-OFF, depending on the stimulus frequency. Neurons with ON-OFF discharge patterns were most common in the 61-kHz region and absent in the high-frequency region. 5. Double tone experiments showed that at short intertone intervals the ON response to the second stimulus or the OFF response to the first stimulus was inhibited. 6. In neuropharmacological experiments, glycine applied to MSO neurons (n = 71) inhibited any tone-evoked response. In the presence of the glycine antagonist strychnine the response patterns changed from phasic to sustained (n = 35) and the neurons responded to both tones presented in double tone experiments independent of the intertone interval (n = 5). The effects of strychnine were reversible. 7. Twenty of 21 neurons tested with sinusoidally amplitude-modulated (SAM) signals exhibited low-pass or band-pass filter characteristics. Tests with SAM signals also revealed a weak temporal summation of inhibition in 13 of the 21 cells tested.(ABSTRACT TRUNCATED AT 400 WORDS)
28
Gittelman, Joshua X., and Bruce L. Tempel. "Kv1.1-Containing Channels Are Critical for Temporal Precision During Spike Initiation." Journal of Neurophysiology 96, no. 3 (September 2006): 1203–14. http://dx.doi.org/10.1152/jn.00092.2005.
Full textAbstract:
Low threshold, voltage-gated potassium currents ( Ikl) are widely expressed in auditory neurons that can fire temporally precise action potentials (APs). In the medial nucleus of the trapezoid body (MNTB), channels containing the Kv1.1 subunit (encoded by the Kcna1 gene) underlie Ikl. Using pharmacology, genetics and whole cell patch-clamp recordings in mouse brain slices, we tested the role of Ikl in limiting AP latency-variability (jitter) in response to trains of single inputs at moderate to high stimulation rates. With dendrotoxin-K (DTX-K, a selective blocker of Kv1.1-containing channels), we blocked Ikl maximally (≈80% with 100 nM DTX-K) or partially (≈50% with 1-h incubation in 3 nM DTX-K). Ikl was similar in 3 nM DTX-K–treated cells and cells from Kcna1−/− mice, allowing a comparison of these two different methods of Ikl reduction. In response to current injection, Ikl reduction increased the temporal window for AP initiation and increased jitter in response to the smallest currents that were able to drive APs. While 100 nM DTX-K caused the largest increases, latency and jitter in Kcna1 −/ − cells and in 3 nM DTX-K–treated cells were similar to each other but increased compared with +/+. The near-phenocopy of the Kcna1−/− cells with 3 nM DTX-K shows that acute blockade of a subset of the Kv1.1-containing channels is functionally similar to the chronic elimination of all Kv1.1 subunits. During rapid stimulation (100–500 Hz), Ikl reduction increased jitter in response to both large and small inputs. These data show that Ikl is critical for maintaining AP temporal precision at physiologically relevant firing rates.
29
Han, Donghe, Shurui Chen, Shiqiang Fang, Shiqiong Liu, Meihua Jin, Zhanpeng Guo, Yajiang Yuan, Yansong Wang, Chang Liu, and Xifan Mei. "The Neuroprotective Effects of Muscle-Derived Stem Cells via Brain-Derived Neurotrophic Factor in Spinal Cord Injury Model." BioMed Research International 2017 (2017): 1–11. http://dx.doi.org/10.1155/2017/1972608.
Full textAbstract:
Muscle-derived stem cells (MDSCs) possess multipotent differentiation and self-renewal capacities; however, the effects and mechanism in neuron injury remain unclear. The aim of this study was to investigate the effects of MDSCs on neuron secondary injury, oxidative stress-induced apoptosis. An in vivo study showed the Basso, Beattie, and Bresnahan (BBB) score and number of neurons significantly increased after MDSCs’ transplantation in spinal cord injury (SCI) rats. An in vitro study demonstrated that MDSCs attenuated neuron apoptosis, and the expression of antioxidants was upregulated as well as the ratio of Bcl-2 and Bax in the MNT (MDSCs cocultured with injured neurons) group compared with the NT (injured neurons) group. Both LC3II/LC3I andβ-catenin were enhanced in the MNT group, while XAV939 (aβ-catenin inhibitor) decreased the expression of nuclear erythroid-related factor 2 (Nrf2) and LC3II/LC3I. Moreover, MDSCs became NSE- (neuron-specific enolase-) positive neuron-like cells with brain-derived neurotrophic factor (BDNF) treatment. The correlation analysis indicated that there was a significant relation between the level of BDNF and neuron injury. These findings suggest that MDSCs may protect the spinal cord from injury by inhibiting apoptosis and replacing injured neurons, and the increased BDNF andβ-catenin could contribute to MDSCs’ effects.
30
Chitravanshi, Vineet C., and Hreday N. Sapru. "Mechanism of cardiovascular effects of nociceptin microinjected into the nucleus tractus solitarius of the rat." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 288, no. 6 (June 2005): R1553—R1562. http://dx.doi.org/10.1152/ajpregu.00762.2004.
Full textAbstract:
Microinjections (100 nl) of 0.15, 0.31, 0.62, and 1.25 mmol/l of nociceptin into the medial nucleus tractus solitarius (mNTS) elicited decreases in mean arterial pressure (11 ± 1.8, 20 ± 2.1, 21.5 ± 3.1, and 15.5 ± 1.9 mmHg, respectively) and heart rate (14 ± 2.7, 29 ± 5.5, 39 ± 5.2, and 17.5 ± 3.1 beats/min, respectively). Because maximal responses were elicited by microinjections of 0.62 mmol/l nociceptin, this concentration was used for other experiments. Repeated microinjections of nociceptin (0.62 mmol/l) into the mNTS, at 20-min intervals, did not elicit tachyphylaxis. Bradycardia induced by microinjections of nociceptin into the mNTS was abolished by bilateral vagotomy. The decreases in mean arterial pressure and heart rate elicited by nociceptin into the mNTS were blocked by prior microinjections of the specific ORL1-receptor antagonist [N-Phe1]-nociceptin-(1–13)-NH2 (9 mmol/l). Microinjections of the ORL1-receptor antagonist alone did not elicit a response. Prior combined microinjections of GABAA and GABAB receptor antagonists (2 mmol/l gabazine and 100 mmol/l 2-hydroxysaclofen, respectively) into the mNTS blocked the responses to microinjections of nociceptin at the same site. Prior microinjections of ionotropic glutamate receptor antagonists (2 mmol/l NBQX and 5 mmol/l d-AP7) also blocked responses to nociceptin microinjections into the mNTS. These results were confirmed by direct neuronal recordings. It was concluded that 1) nociceptin inhibits GABAergic neurons in the mNTS, 2) GABAergic neurons may normally inhibit the release of glutamate from the terminals of peripheral afferents in the mNTS, and 3) inhibition of GABAergic neurons by nociceptin results in an increase in the release of glutamate in the mNTS, which in turn elicits depressor and bradycardic responses via activation of ionotropic glutamate receptors on secondary mNTS neurons.
31
Ong, Zhi Yi, Amber L. Alhadeff, and Harvey J. Grill. "Medial nucleus tractus solitarius oxytocin receptor signaling and food intake control: the role of gastrointestinal satiation signal processing." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 308, no. 9 (May 1, 2015): R800—R806. http://dx.doi.org/10.1152/ajpregu.00534.2014.
Full textAbstract:
Central oxytocin (OT) administration reduces food intake and its effects are mediated, in part, by hindbrain oxytocin receptor (OT-R) signaling. The neural substrate and mechanisms mediating the intake inhibitory effects of hindbrain OT-R signaling are undefined. We examined the hypothesis that hindbrain OT-R-mediated feeding inhibition results from an interaction between medial nucleus tractus solitarius (mNTS) OT-R signaling and the processing of gastrointestinal (GI) satiation signals by neurons of the mNTS. Here, we demonstrated that mNTS or fourth ventricle (4V) microinjections of OT in rats reduced chow intake in a dose-dependent manner. To examine whether the intake suppressive effects of mNTS OT-R signaling is mediated by GI signal processing, rats were injected with OT to the 4V (1 μg) or mNTS (0.3 μg), followed by self-ingestion of a nutrient preload, where either treatment was designed to be without effect on chow intake. Results showed that the combination of mNTS OT-R signaling and GI signaling processing by preload ingestion reduced chow intake significantly and to a greater extent than either stimulus alone. Using enzyme immunoassay, endogenous OT content in mNTS-enriched dorsal vagal complex (DVC) in response to ingestion of nutrient preload was measured. Results revealed that preload ingestion significantly elevated endogenous DVC OT content. Taken together, these findings provide evidence that mNTS neurons are a site of action for hindbrain OT-R signaling in food intake control and that the intake inhibitory effects of hindbrain mNTS OT-R signaling are mediated by interactions with GI satiation signal processing by mNTS neurons.
32
Huo, Lihong, Lisa Maeng, Christian Bjørbæk, and Harvey J. Grill. "Leptin and the Control of Food Intake: Neurons in the Nucleus of the Solitary Tract Are Activated by Both Gastric Distension and Leptin." Endocrinology 148, no. 5 (May 1, 2007): 2189–97. http://dx.doi.org/10.1210/en.2006-1572.
Full textAbstract:
Leptin reduces food intake by an unspecified mechanism. Studies show that forebrain ventricular leptin delivery increases the inhibitory effects of gastrointestinal (GI) stimulation on intake and amplifies the electrophysiological response to gastric distension in neurons of the medial subnucleus of the nucleus tractus solitarius (mNTS). However, forebrain ventricular delivery leaves unspecified the neuroanatomical site(s) mediating leptin’s effect on intake. Detailed anatomical analysis in rats and mice by phosphorylated signal transducer and activator of transcription 3 immunohistochemistry shows that hindbrain leptin-responsive neurons are located exclusively within the mNTS. Here, we investigate 1) whether leptin and gastric distension affect the same mNTS neurons and 2) whether the intake-inhibitory action of gastric distension is potentiated by hindbrain leptin delivery. Twenty-five minutes after gastric balloon distension or sham distension, rats were injected with leptin or vehicle and killed 35 min later. Double-fluorescent immunohistochemistry for phosphorylated signal transducer and activator of transcription 3 and c-Fos revealed that about 40% of leptin-responsive cells also respond to gastric distension. A paradigm was then developed to examine the relationship between leptin and gastric distension volume on intake inhibition. At subthreshold levels, hindbrain ventricular leptin or distension volume were without effect. When combined, an interaction occurred that significantly reduced food intake. We conclude that 1) leptin-responsive neurons in the hindbrain are primarily located in the mNTS at the level of the area postrema, a key vagal afferent projection zone of the GI system; 2) a significant proportion of leptin-responsive neurons in the mNTS are activated by stomach distension; and 3) leptin delivered to the hindbrain is sufficient to potentiate the intake-suppressive effects of an otherwise ineffective volume of gastric distension. These results are consistent with the hypothesis that leptin acts directly on neurons within the mNTS to reduce food intake through an interaction with GI signal processing.
33
Shihara, Miwako, Nobuaki Hori, Yoshitaka Hirooka, Kenichi Eshima, Norio Akaike, and Akira Takeshita. "Cholinergic systems in the nucleus of the solitary tract of rats." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 276, no. 4 (April 1, 1999): R1141—R1148. http://dx.doi.org/10.1152/ajpregu.1999.276.4.r1141.
Full textAbstract:
The pharmacological and physiological properties of excitatory amino acid and ACh systems in the nucleus of the solitary tract (NTS) were studied in slices of rat brain stem by extracellular and intracellular recordings from neurons activated by solitary tract (ST) stimulation. These neurons were characterized as having several long dendrites with multiple varicosities. Synaptic activation of the medial NTS (mNTS) neurons by ST stimulation was mediated by non- N-methyl-d-aspartate (NMDA) glutamate (Glu) receptors, because the excitation was blocked by 6-cyano-7-nitro-quinoxaline-2,3-dione but not by NMDA, nicotinic, or muscarinic antagonists. Identified mNTS neurons were excited by iontophoresis of both Glu and ACh. The most sensitive region of the cell was on the dendrites ∼100 μm from the cell body for both putative neurotransmitters. Nicotinic and/or muscarinic excitatory ACh responses were detected on the mNTS neurons. Our observations suggest that both types of ACh receptors may contribute to the attenuation of the baroreceptor reflex, but the functional correlation of this receptor profile remains to be determined.
34
Wang, Gang, Christal G. Coleman, Michael J. Glass, Ping Zhou, Qi Yu, Laibaik Park, Josef Anrather, Virginia M. Pickel, and Costantino Iadecola. "Angiotensin II type 2 receptor-coupled nitric oxide production modulates free radical availability and voltage-gated Ca2+ currents in NTS neurons." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 302, no. 9 (May 1, 2012): R1076—R1083. http://dx.doi.org/10.1152/ajpregu.00571.2011.
Full textAbstract:
The medial region of the nucleus tractus solitarius (mNTS) is a key brain stem site controlling cardiovascular function, wherein ANG II modulates neuronal L-type Ca2+ currents via activation of ANG II type 1 receptors (AT1R) and production of reactive oxygen species (ROS). ANG II type 2 receptors (AT2R) induce production of nitric oxide (NO), which may interact with ROS and modulate AT1R signaling. We sought to determine whether AT2R-mediated NO production occurs in mNTS neurons and, if so, to elucidate the NO source and the functional interaction with AT1R-induced ROS or Ca2+ influx. Electron microscopic (EM) immunolabeling showed that AT2R and neuronal NO synthase (nNOS) are coexpressed in neuronal somata and dendrites receiving synapses in the mNTS. In the presence of the AT1R antagonist losartan, ANG II increased NO production in isolated mNTS neurons, an effect blocked by the AT2R antagonist PD123319, but not the angiotensin (1–7) antagonist D-Ala. Studies in mNTS neurons of nNOS-null or endothelial NOS (eNOS)-null mice established nNOS as the source of NO. ANG II-induced ROS production was enhanced by PD123319, the NOS inhibitor NG-nitro-l-arginine (LNNA), or in nNOS-null mice. Moreover, in the presence of losartan, ANG II reduced voltage-gated L-type Ca2+ current, an effect blocked by PD123319 or LNNA. We conclude that AT2R are closely associated and functionally coupled with nNOS in mNTS neurons. The resulting NO production antagonizes AT1R-mediated ROS and dampens L-type Ca2+ currents. The ensuing signaling changes in the NTS may counteract the deleterious effects of AT1R on cardiovascular function.
35
Schild, J. H., J. W. Clark, C. C. Canavier, D. L. Kunze, and M. C. Andresen. "Afferent synaptic drive of rat medial nucleus tractus solitarius neurons: dynamic simulation of graded vesicular mobilization, release, and non-NMDA receptor kinetics." Journal of Neurophysiology 74, no. 4 (October 1, 1995): 1529–48. http://dx.doi.org/10.1152/jn.1995.74.4.1529.
Full textAbstract:
1. We have developed a comprehensive mathematical model of an afferent synaptic connection to the soma of a medial nucleus tractus solitarius (mNTS) neuron. Model development is based on numerical fits to quantitative data recorded in our laboratory. This work is part of a continuing collaborative effort aimed at identifying and characterizing the mechanisms responsible for the non-linear integrative properties of this first synapse in the baroreceptor reflex. 2. The complete model consists of three major parts: 1) a Hodgkin-Huxley (HH)-type membrane model of the prejunctional sensory terminal bouton; 2) a multistage model describing vesicular storage, adenosine 3',5'-cyclic monophosphate (cAMP)- and Ca(2+)-dependent mobilization, release and recycling; and 3) a HH-type membrane model of the postjunctional mNTS cell that includes descriptions for a desensitizing non-N-methyl-D-aspartate (NMDA) ionic current that is responsible for the fast excitatory postsynaptic potentials (EPSPs) observed in mNTS cells. The membrane models for both the terminal bouton and the mNTS neuron are coupled to separate lumped fluid compartment models describing intracellular Ca2+ ion concentration dynamics. 3. Our modeling strategy is twofold. The first is to validate model performance by reproducing a wide variety of experimental data both from our laboratory and from the literature. The second is to explore the functional aspects of the model in order to gain a greater appreciation for the balance between presynaptic mechanisms (e.g., terminal membrane properties and vesicular dynamics) and postsynaptic mechanisms (e.g., non-NMDA receptor kinetics and neuronal dynamics) that underlie the afferent synaptic drive of mNTS neurons. 4. The model accurately reproduces EPSP dynamics recorded with the use of a wide range of stimulus protocols. The model can also mirror the unique pattern of graded frequency- and use-dependent reduction in peak EPSP magnitude observed experimentally through 60 s of constant, suprathreshold synaptic activation. We demonstrate how vesicular mobilization, recycling, and receptor kinetics can function synergistically in establishing synaptic transfer. Furthermore, we show that by allowing the aggregate rate of vesicle mobilization to respond in a use-dependent manner, it is possible to compensate for the attenuating affects of desensitization at elevated rates of stimulation. 5. Our simulations indicate that the low-frequency characteristics of this synapse are dominated by vesicular dynamics, whereas the high-frequency properties arise from a combination of Ca(2+)-dependent vesicular mobilization and the kinetics of the non-NMDA receptor. Desensitization can influence the peak magnitude and decay time of the EPSP, thereby affecting synaptic throughput. However, we demonstrate that, as the time course of neurotransmitter in the synaptic cleft decreases, the influence of desensitization should be somewhat diminished. As a result, the effective bandwidth of the synapse increases and becomes limited by the gating characteristics of the non-NMDA channel. 6. The model also includes a neuromodulatory aspect in that the frequency response of the synapse can be modulated by an adenylate cyclase-mediated regulatory mechanism. Although our simulations indicate the behavior of a limited number of possible neuromodulatory agents, the results demonstrate the pivotal role such agents could play in modifying synaptic transfer characteristics presynaptically. 7. Both continuous and burst-mode tract stimulation evoke patterns of action potentials in spontaneously active mNTS neurons that are mimicked very well by our model. Our simulations demonstrate that, as the rate of stimulation increases beyond approximately 20-30 Hz, the inherent low-pass frequency-response characteristics of the synapse limit the overall dynamic range of the mNTS neuron, causing the postsynaptic cell to “entrain” at frequencies within its normal operating range.
36
Chitravanshi, Vineet C., and Hreday N. Sapru. "Cardiovascular responses elicited by a new endogenous angiotensin in the nucleus tractus solitarius of the rat." American Journal of Physiology-Heart and Circulatory Physiology 300, no. 1 (January 2011): H230—H240. http://dx.doi.org/10.1152/ajpheart.00861.2010.
Full textAbstract:
Cardiovascular effects of angiotensin-(1–12) [ANG-(1–12)] were studied in the medial nucleus of the tractus solitarius (mNTS) in anesthetized, artificially ventilated, adult male Wistar rats. Microinjections (100 nl) of ANG-(1–12) (0.06 mM) into the mNTS elicited maximum decreases in mean arterial pressure (MAP; 34 ± 5.8 mmHg) and heart rate (HR; 39 ± 3.7 beats/min). Bilateral vagotomy abolished ANG-(1–12)-induced bradycardia. Efferent greater splanchnic nerve activity was decreased by microinjections of ANG-(1–12) into the mNTS. Blockade of ANG type 1 receptors (AT1Rs; using ZD-7155 or L-158,809), but not ANG type 2 receptors (AT2Rs; using PD-123319), significantly attenuated ANG-(1–12)-induced cardiovascular responses. Simultaneous inhibition of both angiotensin-converting enzyme (ACE; using captopril) and chymase (using chymostatin) completely blocked the effects of ANG-(1–12). Microinjections of A-779 [ANG-(1–7) antagonist] did not attenuate ANG-(1–12)-induced responses. Pressure ejection of ANG-(1–12) (0.06 mM, 2 nl) caused excitation of barosensitive mNTS neurons, which was blocked by prior application of the AT1R antagonist. ANG-(1–12)-induced excitation of mNTS neurons was also blocked by prior sequential applications of captopril and chymostatin. These results indicate that 1) microinjections of ANG-(1–12) into the mNTS elicited depressor and bradycardic responses by exciting barosensitive mNTS neurons; 2) the decreases in MAP and HR were mediated via sympathetic and vagus nerves, respectively; 3) AT1Rs, but not AT2Rs, mediated these actions of ANG-(1–12); 4) the responses were mediated via the conversion of ANG-(1–12) to ANG II and both ACE and chymase were involved in this conversion; and 5) ANG-(1–7) was not one of the metabolites of ANG-(1–12) in the mNTS.
37
Johnson, S. M., and R. B. Felder. "Effects of aging on the intrinsic membrane properties of medial NTS neurons of Fischer-344 rats." Journal of Neurophysiology 70, no. 5 (November 1, 1993): 1975–87. http://dx.doi.org/10.1152/jn.1993.70.5.1975.
Full textAbstract:
1. Recent studies have demonstrated that the arterial baroreflex is imparied with aging and have implicated central components of the baroreflex arc in this autonomic dysfunction. Neurons in the medial portion of the nucleus tractus solitarius (mNTS) receive a major input from the arterial baroreceptors. The present study was undertaken to characterize the intrinsic membrane properties of mNTS neurons in young rats and to test the hypothesis that these properties are altered with aging. An in vitro brain stem slice preparation was used to record intracellularly from mNTS neurons; passive membrane properties, action potential characteristics, and repetitive firing properties were examined and compared. 2. Neurons in the mNTS of young (3-5 mo old) Fischer-344 rats (F-344; n = 35) had a resting membrane potential of -57 +/- 6.9 mV (mean +/- SD), a membrane time constant of 18 +/- 9.0 ms, and an input resistance of 110 +/- 60 m omega. Action potential amplitude was 81 +/- 7.5 mV with a duration at half-height of 0.83 +/- 0.15 ms. The spontaneous firing rate in 24 cells was 4.3 +/- 2.9 Hz. The amplitude and duration of the action potential afterhyperpolarization (AHP) were 6.6 +/- 3.0 mV and 64 +/- 34 ms, respectively. All neurons expressed spike frequency adaptation, action potential AHP, and posttetanic hyperpolarization. Delayed excitation and postinhibitory rebound were present in 34 and 14% of neurons tested, respectively. Neurons from adult (10-12 mo old) F-344 rats (n = 34) were similar to the young F-344 rats with respect to all of these variables. 3. Neurons from aged (21-24 mo old) F-344 (n = 32) were similar to those from young and adult rats, but there were two potentially important differences: the mean input resistance of the aged neurons was higher (170 +/- 150 M omega), with a larger proportion (46% of aged neurons vs. 20% of young neurons and 21% of adult neurons) having input resistances > 150 M omega; and there was a tendency for a smaller percentage of aged neurons (16% of aged neurons vs. 34% of young neurons and 29% of adult neurons) to express delayed excitation. 4. The potential significance of a high input resistance was tested by comparing the steady-state current-voltage (I-V) relationships and the frequency-current (f-I) relationships among low-resistance (1-100 M omega), medium-resistance (101-200 M omega).(ABSTRACT TRUNCATED AT 400 WORDS)
38
Alhadeff, Amber L., and Harvey J. Grill. "Hindbrain nucleus tractus solitarius glucagon-like peptide-1 receptor signaling reduces appetitive and motivational aspects of feeding." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 307, no. 4 (August 15, 2014): R465—R470. http://dx.doi.org/10.1152/ajpregu.00179.2014.
Full textAbstract:
Central glucagon-like peptide-1 receptor (GLP-1R) signaling reduces food intake by affecting a variety of neural processes, including those mediating satiation, motivation, and reward. While the literature suggests that separable neurons and circuits control these processes, this notion has not been adequately investigated. The intake inhibitory effects of GLP-1R signaling in the hindbrain medial nucleus tractus solitarius (mNTS) have been attributed to interactions with vagally transmitted gastrointestinal satiation signals that are also processed by these neurons. Here, behavioral and pharmacological techniques are used to test the novel hypothesis that the reduction of food intake following mNTS GLP-1R stimulation also results from effects on food-motivated appetitive behaviors. Results show that mNTS GLP-1R activation by microinjection of exendin-4, a long-acting GLP-1R agonist, reduced 1) intake of a palatable high-fat diet, 2) operant responding for sucrose under a progressive ratio schedule of reinforcement and 3) the expression of a conditioned place preference for a palatable food. Together, these data demonstrate that the intake inhibitory effects of mNTS GLP-1R signaling extend beyond satiation and include effects on food reward and motivation that are typically ascribed to midbrain and forebrain neurons.
39
Mimee, Andrea, Pauline M. Smith, and Alastair V. Ferguson. "Nesfatin-1 influences the excitability of neurons in the nucleus of the solitary tract and regulates cardiovascular function." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 302, no. 11 (June 1, 2012): R1297—R1304. http://dx.doi.org/10.1152/ajpregu.00266.2011.
Full textAbstract:
Nesfatin-1 has been identified as one of the most potent centrally acting anorexigenic peptides, and it has also been shown to play important roles in the control of cardiovascular function. In situ hybridization and immunohistochemical studies have revealed the expression of nesfatin-1 throughout the brain and, in particular, in the medullary autonomic gateway known as the nucleus of the solitary tract (NTS). The present study was thus undertaken to explore the cellular correlates and functional roles of nesfatin-1 actions in the medial NTS (mNTS). Using current-clamp electrophysiology recordings from mNTS neurons in slice preparation, we show that bath-applied nesfatin-1 directly influences the excitability of the majority of mNTS neurons by eliciting either depolarizing (42%, mean: 7.8 ± 0.8 mV) or hyperpolarizing (21%, mean: −8. 2 ± 1.0 mV) responses. These responses were observed in all electrophysiologically defined cell types in the NTS and were site specific and concentration dependent. Furthermore, post hoc single cell reverse transcriptase polymerase reaction revealed a depolarizing action of nesfatin-1 on NPY and nucleobindin-2-expressing mNTS neurons. We have also correlated these actions of nesfatin-1 on neuronal membrane potential with physiological outcomes, using in vivo microinjection techniques to demonstrate that nesfatin-1 microinjected into the mNTS induces significant increases in both blood pressure (mean AUC = 3354.1 ± 750.7 mmHg·s, n = 6) and heart rate (mean AUC = 164.8 ± 78.5 beats, n = 6) in rats. Our results provide critical insight into the circuitry and physiology involved in the profound effects of nesfatin-1 and highlight the NTS as a key structure mediating these autonomic actions.
40
Kanoski, Scott E., Shiru Zhao, Douglas J. Guarnieri, Ralph J. DiLeone, Jianqun Yan, Bart C. De Jonghe, Kendra K. Bence, Matthew R. Hayes, and Harvey J. Grill. "Endogenous leptin receptor signaling in the medial nucleus tractus solitarius affects meal size and potentiates intestinal satiation signals." American Journal of Physiology-Endocrinology and Metabolism 303, no. 4 (August 15, 2012): E496—E503. http://dx.doi.org/10.1152/ajpendo.00205.2012.
Full textAbstract:
Leptin receptor (LepRb) signaling in the hindbrain is required for energy balance control. Yet the specific hindbrain neurons and the behavioral processes mediating energy balance control by hindbrain leptin signaling are unknown. Studies here employ genetic [adeno-associated virally mediated RNA interference (AAV-RNAi)] and pharmacological methodologies to specify the neurons and the mechanisms through which hindbrain LepRb signaling contributes to the control of food intake. Results show that AAV-RNAi-mediated LepRb knockdown targeting a region encompassing the mNTS and area postrema (AP) (mNTS/AP LepRbKD) increases overall cumulative food intake by increasing the size of spontaneous meals. Other results show that pharmacological hindbrain leptin delivery and RNAi-mediated mNTS/AP LepRb knockdown increased and decreased the intake-suppressive effects of intraduodenal nutrient infusion, respectively. These meal size and intestinally derived signal amplification effects are likely mediated by LepRb signaling in the mNTS and not the AP, since 4th icv and mNTS parenchymal leptin (0.5 μg) administration reduced food intake, whereas this dose did not influence food intake when injected into the AP. Overall, these findings deepen the understanding of the distributed neuronal systems and behavioral mechanisms that mediate the effects of leptin receptor signaling on the control of food intake.
41
Kasamatsu, Ken, Vineet C. Chitravanshi, and Hreday N. Sapru. "Depressor and bradycardic responses to microinjections of endomorphin-2 into the NTS are mediated via ionotropic glutamate receptors." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 287, no. 4 (October 2004): R715—R728. http://dx.doi.org/10.1152/ajpregu.00642.2003.
Full textAbstract:
The presence of endomorphin-like immunoreactivity has been reported in the nucleus tractus solitarius (NTS). It was hypothesized that endomorphins may play a role in cardiovascular regulation in the medial subnucleus of the NTS (mNTS). Endomorphin-2 (E-2, 0.1–4 mmol/l) was microinjected (100 nl) into the mNTS of urethane-anesthetized, artificially ventilated, adult male Wistar rats. E-2 (0.2 mmol/l) elicited decreases in mean arterial pressure (40 ± 3.5 mmHg) and heart rate (50 ± 7.0 beats/min). These responses were blocked by prior microinjections of naloxonazine (1 mmol/l) into the mNTS. Responses to microinjections of E-2 into the mNTS were abolished by prior combined microinjections of d-2-amino-7-phosphonoheptanoic acid (an NMDA receptor antagonist, 5 mmol/l) and 2,3-dioxo-6-nitro-1,2,3,4-tetrahydrobenzo[ f]quinoxaline-7-sulfonamide disodium (a non-NMDA receptor antagonist, 2 mmol/l) into the mNTS. These results were confirmed by extracellular neuronal recordings. Blockade of GABA receptors in the mNTS by prior combined microinjections of gabazine (a GABAA receptor antagonist, 2 mmol/l) and 2-hydroxysaclofen (a GABAB receptor antagonist, 100 mmol/l) also blocked the responses to E-2. It was concluded that 1) the depressor and bradycardic responses to microinjections of E-2 into the mNTS are mediated via μ1-opioid receptors as well as ionotropic glutamate receptors, 2) GABAergic neurons in the mNTS, which may inhibit the release of glutamate from nerve terminals, are inhibited by E-2 via μ1-opioid receptors, and 3) disinhibition caused by the inhibition of GABAergic neurons by E-2 may result in an increase in the glutamate release from nerve terminals, which, in turn, may elicit depressor and bradycardic responses.
42
Herman, Melissa A., Maureen T. Cruz, Niaz Sahibzada, Joseph Verbalis, and Richard A. Gillis. "GABA signaling in the nucleus tractus solitarius sets the level of activity in dorsal motor nucleus of the vagus cholinergic neurons in the vagovagal circuit." American Journal of Physiology-Gastrointestinal and Liver Physiology 296, no. 1 (January 2009): G101—G111. http://dx.doi.org/10.1152/ajpgi.90504.2008.
Full textAbstract:
It has been proposed that there is an “apparent monosynaptic” connection between gastric vagal afferent nerve terminals and inhibitory projection neurons in the nucleus tractus solitarius (NTS) and that two efferent parallel pathways from the dorsal motor nucleus of the vagus (DMV) influence peripheral organs associated with these reflexes ( 6 ). The purpose of our study was to verify the validity of these views as they relate to basal control of gastric motility. To test the validity of a direct connection of vagal afferent terminals (known to release l-glutamate) directly impacting second-order projection neurons, we evaluated the effect of GABAA receptor blockade in the area of the medial subnucleus of the tractus solitarius (mNTS) on gastric motility. Microinjection of bicuculline methiodide into the mNTS produced robust decreases in gastric motility (−1.6 ± 0.2 mmHg, P < 0.05, n = 23), which were prevented by cervical vagotomy and by pretreatment with kynurenic acid microinjected into the mNTS. Kynurenic acid per se had no effect on gastric motility. However, after GABAA receptor blockade in the mNTS, kynurenic acid produced a robust increase in gastric motility. To test for the contribution of two parallel efferent DMV pathways, we assessed the effect of either intravenous atropine methylbromide or NG-nitro-l-arginine methyl ester on baseline motility and on decreases in gastric motility induced by GABAA receptor blockade in the mNTS. Only atropine methylbromide altered baseline motility and prevented the effects of GABAA receptor blockade on gastric motility. Our data demonstrate the presence of intra-NTS GABAergic signaling between the vagal afferent nerve terminals and inhibitory projection neurons in the NTS and that the cholinergic-cholinergic excitatory pathway comprises the functionally relevant efferent arm of the vagovagal circuit.
43
Han, Daniel, Jason Gordon, Steven Nguyen, and Michael D. Turner. "Melanotic Neuroectodermal Tumor of Infancy with a Negative VMA: A Case Report and Review of the Presentation, Etiology, and Management." Craniomaxillofacial Trauma & Reconstruction Open 3, no. 1 (January 2019): s—0039–1693037. http://dx.doi.org/10.1055/s-0039-1693037.
Full textAbstract:
Melanotic neuroectodermal tumor of infancy (MNTI) is a rare rapidly growing tumor, which although benign, it is locally aggressive and destructive to the surrounding structures. The maxilla is the most commonly involved site, and MNTI is known to be locally aggressive if left untreated. Neural crest cells differentiate into sympathetic neurons that produce catecholamines. These catecholamines degrade, leaving the residual products homovanillic acid and vanillylmandelic acid (VMA). Because of this, patients with MNTI may have high levels of VMA in their urine and should be tested for this if MNTI is suspected. This is a presentation of a healthy 6-month-old girl with a 1-month history of swelling in the anterior maxilla. A computed tomography (CT) scan revealed a radiolucent lesion of the anterior maxilla, which following biopsy, was histologically diagnosed as MNTI, although the patient had normal levels of VMA. A three-dimensional model was reconstructed from the CT scan and used in planning surgical excision. A differential diagnosis of MNTI should be included in cases of infants presenting with fast growing expansile swelling in the head and neck region.
44
Ma, Sheng-Xing, Qun Fang, Brian Morgan, Michael G. Ross, and Conrad R. Chao. "Cardiovascular regulation and expressions of NO synthase-tyrosine hydroxylase in nucleus tractus solitarius of ovine fetus." American Journal of Physiology-Heart and Circulatory Physiology 284, no. 4 (April 1, 2003): H1057—H1063. http://dx.doi.org/10.1152/ajpheart.00718.2002.
Full textAbstract:
The purpose of this study was to examine cardiovascular responses to fourth cerebral ventricle (4V) administration of nitroglycerin (NTG) or an inhibitor of nitric oxide (NO) synthase (NOS) in the near-term ovine and to determine whether, during birth, neuronal NOS (nNOS) is induced in noradrenergic A1 neurons in the medial nucleus tractus solitarius (mNTS). In chronically instrumented fetal sheep, 4V injection of NTG (1.2 nmol), an NO donor, produced an arterial blood depressor and a moderate decrease in heart rate. Arterial blood pressure is increased by 4V administration of N G-nitro-l-arginine methyl ester (10 nmnol), an inhibitor of NOS, in fetuses. Sections of the medulla from fetuses and newborn lambs were examined by using immunolabeling with tyrosine hydroxylase (TH) antibody combined with NADPH diaphorase (NADPHd) histochemistry, a marker of nNOS activity. The NADPHd-positive cells and TH-positive cells containing NADPHd reactivity were significantly increased in the mNTS of newborns compared with the fetuses. The results suggest that during birth, there is upregulation of NADPHd/nNOS in the noradrenergic neurons of mNTS resulting in a centrally mediated reduction of fetal arterial blood pressure.
45
Herman, Melissa A., Alisa Alayan, Niaz Sahibzada, Barbara Bayer, Joseph Verbalis, Kenneth L. Dretchen, and Richard A. Gillis. "μ-Opioid receptor stimulation in the medial subnucleus of the tractus solitarius inhibits gastric tone and motility by reducing local GABA activity." American Journal of Physiology-Gastrointestinal and Liver Physiology 299, no. 2 (August 2010): G494—G506. http://dx.doi.org/10.1152/ajpgi.00038.2010.
Full textAbstract:
We examined the effects of altering μ-opioid receptor (MOR) activity in the medial subnucleus of the tractus solitarius (mNTS) on several gastric end points including intragastric pressure (IGP), fundus tone, and the receptive relaxation reflex (RRR). Microinjection of the MOR agonist [d-Ala2,MePhe4,Gly(ol)5]enkephalin (DAMGO; 1–10 fmol) into the mNTS produced dose-dependent decreases in IGP. Microinjection of the endogenous MOR agonists endomorphin-1 and endomorphin-2 (20 fmol) into the mNTS mimicked the effects of 10 fmol DAMGO. Microinjection of 1 and 100 pmol DAMGO into the mNTS produced a triphasic response consisting of an initial decrease, a transient increase, and a persistent decrease in IGP. The increase in IGP appeared to be due to diffusion to the dorsal motor nucleus of the vagus. The effects of 10 fmol DAMGO in the mNTS were blocked by vagotomy and by blockade of MORs, GABAAreceptors, and ionotropic glutamate receptors in the mNTS. The RRR response was abolished by bilateral microinjection of the opioid receptor antagonist naltrexone into the mNTS and reduced by intravenous administration of naltrexone. Our data demonstrate that 1) activation of MORs in the mNTS with femtomole doses of agonist inhibits gastric motility, 2) the mechanism of MOR effects in the mNTS is through suppression of local GABA activity, and 3) blockade of MORs in the mNTS prevents the RRR response. These data suggest that opioids play an important role in mediating a vagovagal reflex through release of an endogenous opioid in the mNTS, which, in turn, inhibits ongoing local GABA activity and allows vagal sensory input to excite second-order mNTS neurons.
46
Blevins, James E., Michael W. Schwartz, and Denis G. Baskin. "Evidence that paraventricular nucleus oxytocin neurons link hypothalamic leptin action to caudal brain stem nuclei controlling meal size." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 287, no. 1 (July 2004): R87—R96. http://dx.doi.org/10.1152/ajpregu.00604.2003.
Full textAbstract:
Hindbrain projections of oxytocin neurons in the parvocellular paraventricular nucleus (pPVN) are hypothesized to transmit leptin signaling from the hypothalamus to the nucleus of the solitary tract (NTS), where satiety signals from the gastrointestinal tract are received. Using immunocytochemistry, we found that an anorectic dose of leptin administered into the third ventricle (3V) increased twofold the number of pPVN oxytocin neurons that expressed Fos. Injections of fluorescent cholera toxin B into the NTS labeled a subset of pPVN oxytocin neurons that expressed Fos in response to 3V leptin. Moreover, 3V administration of an oxytocin receptor antagonist, [d-(CH2)5,Tyr(Me)2,Orn8]-vasotocin (OVT), attenuated the effect of leptin on food intake over a 0.5- to 4-h period ( P < 0.05). Furthermore, to determine whether oxytocin contributes to leptin's potentiation of Fos activation within NTS neurons in response to CCK, we counted the number of Fos-positive neurons in the medial NTS (mNTS) after 3V administration of OVT before 3V leptin and intraperitoneal CCK-8 administration. OVT resulted in a significant 37% decrease ( P < 0.05) in the potentiating effect of leptin on CCK activation of mNTS neuronal Fos expression. Furthermore, 4V OVT stimulated 2-h food intake by 43% ( P < 0.01), whereas 3V OVT at the same dose was ineffective. These findings suggest that release of oxytocin from a descending pPVN-to-NTS pathway contributes to leptin's attenuation of food intake by a mechanism that involves the activation of pPVN oxytocin neurons by leptin, resulting in increased sensitivity of NTS neurons to satiety signals.
47
Kobashi, Motoi, Yuichi Shimatani, Masako Fujita, Yoshihiro Mitoh, Ryusuke Yoshida, and Ryuji Matsuo. "The Effects of Mutual Interaction of Orexin-A and Glucagon-Like Peptide-1 on Reflex Swallowing Induced by SLN Afferents in Rats." International Journal of Molecular Sciences 21, no. 12 (June 22, 2020): 4422. http://dx.doi.org/10.3390/ijms21124422.
Full textAbstract:
(1) Background: Our previous studies revealed that orexin-A, an appetite-increasing peptide, suppressed reflex swallowing via the commissural part of the nucleus tractus solitarius (cNTS), and that glucagon-like peptide-1 (GLP-1), an appetite-reducing peptide, also suppressed reflex swallowing via the medial nucleus of the NTS (mNTS). In this study, we examined the mutual interaction between orexin-A and GLP-1 in reflex swallowing. (2) Methods: Sprague–Dawley rats under urethane–chloralose anesthesia were used. Swallowing was induced by electrical stimulation of the superior laryngeal nerve (SLN) and was identified by the electromyographic (EMG) signals obtained from the mylohyoid muscle. (3) Results: The injection of GLP-1 (20 pmol) into the mNTS reduced the swallowing frequency and extended the latency of the first swallow. These suppressive effects of GLP-1 were not observed after the fourth ventricular administration of orexin-A. After the injection of an orexin-1 receptor antagonist (SB334867) into the cNTS, an ineffective dose of GLP-1 (6 pmol) into the mNTS suppressed reflex swallowing. Similarly, the suppressive effects of orexin-A (1 nmol) were not observed after the injection of GLP-1 (6 pmol) into the mNTS. After the administration of a GLP-1 receptor antagonist (exendin-4(5-39)), an ineffective dose of orexin-A (0.3 nmol) suppressed reflex swallowing. (4) Conclusions: The presence of reciprocal inhibitory connections between GLP-1 receptive neurons and orexin-A receptive neurons in the NTS was strongly suggested.
48
Jin, Young-Ho, Timothy W. Bailey, Mark W. Doyle, Bai-yan Li, Kyoung S. K. Chang, John H. Schild, David Mendelowitz, and Michael C. Andresen. "Ketamine Differentially Blocks Sensory Afferent Synaptic Transmission in Medial Nucleus Tractus Solitarius (mNTS)." Anesthesiology 98, no. 1 (January 1, 2003): 121–32. http://dx.doi.org/10.1097/00000542-200301000-00021.
Full textAbstract:
Background Ketamine increases blood pressure and heart rate by unknown mechanisms, but studies suggest that an intact central nervous system and arterial baroreceptors are required. In the brain stem, medial nucleus tractus solitarius receives afferents from nodose neurons that initiate cardiovascular autonomic reflexes. Here, the authors assessed ketamine actions on afferent medial nucleus tractus solitarius synaptic transmission. Methods Ketamine was applied to horizontally sliced brain stems. Solitary tract (ST) stimulation evoked excitatory postsynaptic currents (eEPSCs) in medial nucleus tractus solitarius neurons. Capsaicin (200 nm) block of ST eEPSCs sorted neurons into sensitive (n = 19) and resistant (n = 23). In nodose ganglion slices, shocks to the peripheral vagal trunk activated afferent action potentials in sensory neurons classified by conduction velocities and capsaicin. Results Ketamine potently (10-100 mciro m) blocked small, ST-evoked -methyl-d-aspartate synaptic currents found only in a subset of capsaicin-resistant neurons (6 of 12). Surprisingly, ketamine reversibly inhibited ST eEPSC amplitudes and induced synaptic failure at lower concentrations in capsaicin-sensitive than in capsaicin-resistant neurons (P < 0.005; n = 11 and 11). Spontaneous EPSCs using non- -methyl-d-aspartate receptors were insensitive even to 1-3 mm ketamine, suggesting that ST responses were blocked presynaptically. Similarly, ketamine blocked C-type action potential conduction at lower concentrations than A-type nodose sensory neurons. Conclusion The authors conclude that ketamine inhibits postsynaptic -methyl-d-aspartate receptors and presynaptic afferent processes in medial nucleus tractus solitarius. Unexpectedly, capsaicin-sensitive (C-type), unmyelinated afferents are significantly more susceptible to block than capsaicin-resistant (A-type), myelinated afferents. This differentiation may be related to tetrodotoxin-resistant sodium currents. Since C-type afferents mediate powerful arterial baroreflexes effects, these differential actions may contribute to ketamine-induced cardiovascular dysfunction.
49
Andresen, M. C., and M. Yang. "Dynamics of sensory afferent synaptic transmission in aortic baroreceptor regions on nucleus tractus solitarius." Journal of Neurophysiology 74, no. 4 (October 1, 1995): 1518–28. http://dx.doi.org/10.1152/jn.1995.74.4.1518.
Full textAbstract:
1. Synaptic responses of medial nucleus tractus solitarius (mNTS) neurons to solitary tract (ST) activation were studied in a horizontal brain slice preparation of the rat medulla. Slices included sections of ST sufficiently long that the ST could be electrically activated several millimeters from the recording site of cell bodies in mNTS. 2. Three types of synaptic events were evoked in response to ST stimulation: simple excitatory postsynaptic potentials (EPSPs), simple inhibitory postsynaptic potentials (IPSPs), and complex EPSP-IPSP sequences. Simple EPSPs had substantially shorter latencies than IPSPs (3.39 +/- 0.65 ms, mean +/- SE, n = 42, vs. 5.86 +/- 0.71 ms, n = 6, respectively). 3. EPSP amplitude increased linearly with increasing hyperpolarization, with an extrapolated reversal potential near 0 mV. 4. EPSPs were maximal at < 0.5 Hz of sustained, constant-frequency ST stimulation (n = 14). EPSP amplitude declined to an average of 57.5% of control at 10 Hz after 2 s of sustained stimulation. With 1 min of sustained, 100-Hz stimulation, EPSP amplitude declined to near zero. 5. With stimuli intermittently delivered as 100-ms bursts every 300 ms, generally comparable average EPSPs were evoked during constant and burst patterns of ST stimulation. The amplitude of the initial EPSP in each burst was very well maintained even at intraburst stimulation rates of 100 Hz. 6. At resting membrane potentials, low constant frequencies of ST stimulation (< 5 Hz) reliably elicited action potentials and suppressed spontaneous spiking, but higher frequencies led to spike failures (> 85% at 100 Hz). Between 5 and 10 Hz, this periodic stimulation-suppression cycle clearly entrained action potential activity to the ST stimuli. Similar patterns of current pulses (5 ms) reliably evoked action potentials with each pulse to higher frequencies (50 Hz) without failures, and entrainment was similar to ST stimulation. 7. In a subset of nucleus tractus solitarius (NTS) neurons (3 of 9 studied), bursts of ST stimuli were as much as 50% more effective at transmitting high frequencies (> 10 Hz) of ST stimulation than the equivalent constant frequencies (P < 0.0001). 8. The long-latency simple IPSPs with no preceding EPSPs reversed to become depolarizing at potentials more negative than -62.9 +/- 7.0 mV (n = 5) and were blocked by the non-N-methyl-D-aspartate antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (n = 3). The ST stimulation frequency-response relation of these IPSPs was similar to that for the short-latency EPSP response excited by ST synapses. Thus these IPSPs appear to be activated polysynaptically via a glutamatergic-GABAergic sequence in response to ST activation. 9. The results suggest that sensory afferent synapses in mNTS have limited transmission of high-frequency inputs. Both synaptic transmission and the characteristics of the postsynaptic neuron importantly contribute to the action potential transmission from afferent to NTS neuron and beyond. This overall frequency response limitation may contribute to the accommodation of reflex responses from sensory afferent inputs such as arterial baroreceptors within their physiological discharge frequency range.
50
Herman, Melissa A., Richard A. Gillis, Stefano Vicini, Kenneth L. Dretchen, and Niaz Sahibzada. "Tonic GABAA receptor conductance in medial subnucleus of the tractus solitarius neurons is inhibited by activation of μ-opioid receptors." Journal of Neurophysiology 107, no. 3 (February 2012): 1022–31. http://dx.doi.org/10.1152/jn.00853.2011.
Full textAbstract:
Our laboratory previously reported that gastric activity is controlled by a robust GABAA receptor-mediated inhibition in the medial nucleus of the tractus solitarius (mNTS) ( Herman et al. 2009 ), and that μ-opioid receptor activation inhibits gastric tone by suppression of this GABA signaling ( Herman et al. 2010 ). These data raised two questions: 1) whether any of this inhibition was due to tonic GABAA receptor-mediated conductance in the mNTS; and 2) whether μ-opioid receptor activation suppressed both tonic and phasic GABA signaling. In whole cell recordings from rat mNTS neurons, application of three GABAA receptor antagonists (gabazine, bicuculline, and picrotoxin) produced a persistent reduction in holding current and decrease in population variance or root mean square (RMS) noise, suggesting a blockade of tonic GABA signaling. Application of gabazine at a lower concentration abolished phasic currents, but had no effect on tonic currents or RMS noise. Application of the δ-subunit preferring agonist gaboxadol (THIP) produced a dose-dependent persistent increase in holding current and RMS noise. Pretreatment with tetrodotoxin prevented the action of gabazine, but had no effect on the THIP-induced current. Membrane excitability was unaffected by the selective blockade of phasic inhibition, but was increased by blockade of both phasic and tonic currents. In contrast, activation of tonic currents decreased membrane excitability. Application of the μ-opioid receptor agonist DAMGO produced a persistent reduction in holding current that was not observed following pretreatment with a GABAA receptor antagonist and was not evident in mice lacking the δ-subunit. These data suggest that mNTS neurons possess a robust tonic inhibition that is mediated by GABAA receptors containing the δ-subunit, that determines membrane excitability, and that is partially regulated by μ-opioid receptors.