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Journal articles on the topic 'Glycinergic synaptic transmission'
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1
Betz, H., J. Gomeza, W. Armsen, P. Scholze, and V. Eulenburg. "Glycine transporters: essential regulators of synaptic transmission." Biochemical Society Transactions 34, no. 1 (January 20, 2006): 55–58. http://dx.doi.org/10.1042/bst0340055.
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Glycine is a major inhibitory neurotransmitter in the mammalian CNS (central nervous system). Glycinergic neurotransmission is terminated by the uptake of glycine into glycinergic nerve terminals and neighbouring glial cells. This uptake process is mediated by specific Na+/Cl−-dependent GlyTs (glycine transporters), GlyT1 and GlyT2. GlyT1, in addition, is thought to regulate the concentration of glycine at excitatory synapses containing NMDARs (N-methyl-D-aspartate receptors), which require glycine as a co-agonist. We have analysed the physiological roles and regulation of GlyT1 and GlyT2 by generating transporter-deficient mice and searching for interacting proteins. Our genetic results indicate that at glycinergic synapses, the glial transporter GlyT1 catalyses the removal of glycine from the synaptic cleft, whereas GlyT2 is required for the re-uptake of glycine into nerve terminals, thereby allowing for neurotransmitter reloading of synaptic vesicles. Both GlyT1 and GlyT2 are essential for CNS function, as revealed by the lethal phenotypes of the respective knockout mice. Mice expressing only a single GlyT1 allele are phenotypically normal but may have enhanced NMDAR function. GlyT2 is highly enriched at glycinergic nerve terminals, and Ca2+-triggered exocytosis and internalization are thought to regulate GlyT2 numbers in the pre-synaptic plasma membrane. We have identified different interacting proteins that may play a role in GlyT2 trafficking and/or pre-synaptic localization.
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Awatramani, Gautam B., Rostislav Turecek, and Laurence O. Trussell. "Staggered Development of GABAergic and Glycinergic Transmission in the MNTB." Journal of Neurophysiology 93, no. 2 (February 2005): 819–28. http://dx.doi.org/10.1152/jn.00798.2004.
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Maturation of some brain stem and spinal inhibitory systems is characterized by a shift from GABAergic to glycinergic transmission. Little is known about how this transition is expressed in terms of individual axonal inputs and synaptic sites. We have explored this issue in the rat medial nucleus of the trapezoid body (MNTB). Synaptic responses at postnatal days 5–7 (P5–P7) were small, slow, and primarily mediated by GABAA receptors. By P8–P12, an additional, faster glycinergic component emerged. At these ages, GABAA, glycine, or both types of receptors mediated transmission, even at single synaptic sites. Thereafter, glycinergic development greatly accelerated. By P25, evoked inhibitory postsynaptic currents (IPSCs) were 10 times briefer and 100 times larger than those measured in the youngest group, suggesting a proliferation of synaptic inputs activating fast-kinetic receptors. Glycinergic miniature IPSCs (mIPSCs) increased markedly in size and decay rate with age. GABAergic mIPSCs also accelerated, but declined slightly in amplitude. Overall, the efficacy of GABAergic inputs showed little maturation between P5 and P20. Although gramicidin perforated-patch recordings revealed that GABA or glycine depolarized P5–P7 cells but hyperpolarized P14–P15 cells, the young depolarizing inputs were not suprathreshold. In addition, vesicle-release properties of inhibitory axons also matured: GABAergic responses in immature rats were highly asynchronous, while in older rats, precise, phasic glycinergic IPSCs could transmit even with 500-Hz stimuli. Thus development of inhibition is characterized by coordinated modifications to transmitter systems, vesicle release kinetics, Cl− gradients, receptor properties, and numbers of synaptic inputs. The apparent switch in GABA/glycine transmission was predominantly due to enhanced glycinergic function.
3
Zhang, Bo, Ozgun Gokce, W. Dylan Hale, Nils Brose, and Thomas C. Südhof. "Autism-associated neuroligin-4 mutation selectively impairs glycinergic synaptic transmission in mouse brainstem synapses." Journal of Experimental Medicine 215, no. 6 (May 3, 2018): 1543–53. http://dx.doi.org/10.1084/jem.20172162.
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In human patients, loss-of-function mutations of the postsynaptic cell-adhesion molecule neuroligin-4 were repeatedly identified as monogenetic causes of autism. In mice, neuroligin-4 deletions caused autism-related behavioral impairments and subtle changes in synaptic transmission, and neuroligin-4 was found, at least in part, at glycinergic synapses. However, low expression levels precluded a comprehensive analysis of neuroligin-4 localization, and overexpression of neuroligin-4 puzzlingly impaired excitatory but not inhibitory synaptic function. As a result, the function of neuroligin-4 remains unclear, as does its relation to other neuroligins. To clarify these issues, we systematically examined the function of neuroligin-4, focusing on excitatory and inhibitory inputs to defined projection neurons of the mouse brainstem as central model synapses. We show that loss of neuroligin-4 causes a profound impairment of glycinergic but not glutamatergic synaptic transmission and a decrease in glycinergic synapse numbers. Thus, neuroligin-4 is essential for the organization and/or maintenance of glycinergic synapses.
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Donato, Roberta, and Andrea Nistri. "Relative Contribution by GABA or Glycine to Cl−-Mediated Synaptic Transmission on Rat Hypoglossal Motoneurons In Vitro." Journal of Neurophysiology 84, no. 6 (December 1, 2000): 2715–24. http://dx.doi.org/10.1152/jn.2000.84.6.2715.
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The relative contribution by GABA and glycine to synaptic transmission of motoneurons was investigated using an hypoglossus nucleus slice preparation from neonatal rats. Spontaneous, miniature, or electrically evoked postsynaptic currents (sPSCs, mPSCs, ePSCs, respectively) mediated by glycine or GABA were recorded under whole cell voltage clamp after blocking excitatory glutamatergic transmission with kynurenic acid. The overall majority of Cl−-mediated sPSCs was glycinergic, while only one-third was GABAergic; 70 ± 10% of mPSCs were glycinergic while 22 ± 8% were GABAergic. Tetrodotoxin (TTX) application dramatically reduced the frequency (and slightly the amplitude) of GABAergic events without changing frequency or amplitude of glycinergic sPSCs. These results indicate that, unlike spontaneous GABAergic transmission, glycine-mediated neurotransmission was essentially independent of network activity. There was a consistent difference in the kinetics of GABAergic and glycinergic responses as GABAergic events had significantly slower rise and decay times than glycinergic ones. Such a difference was always present whenever sPSCs, mPSCs, or ePSCs were measured. Finally, GABAergic and glycinergic mPSCs were differentially modulated by activation of glutamate metabotropic receptors (mGluRs), which are abundant in the hypoglossus nucleus. In fact, the broad-spectrum mGluR agonist (±)-1-aminocyclopentane- trans-1,3-dicarboxylic acid (50 μM), which in control solution increased the frequency of both GABAergic and glycinergic sPSCs, enhanced the frequency of glycinergic mPSCs only. These results indicate that on brain stem motoneurons, Cl−-mediated synaptic transmission is mainly due to glycine rather than GABA and that GABAergic and glycinergic events differ in terms of kinetics and pharmacological sensitivity to mGluR activation or TTX.
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Umemiya, M., and A. J. Berger. "Presynaptic inhibition by serotonin of glycinergic inhibitory synaptic currents in the rat brain stem." Journal of Neurophysiology 73, no. 3 (March 1, 1995): 1192–201. http://dx.doi.org/10.1152/jn.1995.73.3.1192.
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1. With the use of a thin brain stem slice preparation, we recorded in visualized neonatal rat hypoglossal motoneurons unitary glycinergic inhibitory postsynaptic currents (IPSCs) that were evoked by extracellular stimulation of nearby interneurons. We found that 10 microM serotonin (5-HT) presynaptically inhibited this glycinergic synaptic transmission by 85.5%. 2. In the somata of presynaptic interneurons, 5-HT1A receptor activation potentiated inwardly rectifying K+ channels and inhibited voltage-activated calcium channels. 3. In contrast, the 5-HT1B receptor was primarily responsible for inhibition of evoked glycinergic IPSCs; a selective 5-HT1B receptor agonist, N-(3-trifluoromethylphenyl)piperazine (TFMPP, 10 microM), inhibited synaptic transmission by 97.3%. On the other hand, 5-HT1A receptor activation by (+)-8-OH-dipropylaminotetralin (8-OHDPAT, 1 microM) inhibited IPSCs by only 24.1%. A 5-HT1A antagonist, 1-(2-methyoxyphenyl)-4-[4-(2-phthalimido)-butyl]piperazine hydrobromide (NAN-190, 1 microM), had no effect on synaptic inhibition by 5-HT. 4. In the presence of tetrodotoxin (TTX) as well as TTX with cadmium (50 microM), we found that 5-HT1B receptor activation by TFMPP reduced the frequency of spontaneous miniature IPSCs (mIPSCs) without changing their mean amplitude. The results suggested that the 5-HT1B receptors activated at the presynaptic terminal inhibited synaptic transmission independent of inhibiting calcium influx through voltage-activated calcium channels. 5. These results indicate that activation of inwardly rectifying K+ channels and inhibition of voltage-activated calcium channels by 5-HT1A receptor activation do not constitute a main pathway for presynaptic inhibition by 5-HT of glycinergic synaptic transmission.(ABSTRACT TRUNCATED AT 250 WORDS)
6
Donato, Roberta, and Andrea Nistri. "Differential Short-Term Changes in GABAergic or Glycinergic Synaptic Efficacy on Rat Hypoglossal Motoneurons." Journal of Neurophysiology 86, no. 2 (August 1, 2001): 565–74. http://dx.doi.org/10.1152/jn.2001.86.2.565.
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Using whole cell patch-clamp recording from hypoglossal motoneurons of a neonatal rat brain slice preparation, we investigated short-term changes in synaptic transmission mediated by GABA or glycine. In 1.5 mM extracellular Ca2+[Ca2+]o, pharmacologically isolated GABAergic or glycinergic currents were elicited by electrical stimulation of the reticular formation. At low stimulation frequency, glycinergic currents were larger and faster than GABAergic ones. GABAergic currents were strongly facilitated by pulse trains at 5 or 10 Hz without apparent depression. This phenomenon persisted after pharmacological block of GABABreceptors. Glycinergic currents were comparatively much less enhanced than GABAergic currents. One possible mechanism to account for this difference is that GABAergic currents decayed so slowly that consecutive responses summated over an incrementing baseline. However, while synaptic summation appeared at ≥10-Hz stimulation, at 5 Hz strong facilitation developed with minimal summation of GABA-mediated currents. Glycinergic currents decayed so fast that summation was minimal. As [Ca2+]o is known to shape short-term synaptic changes, we examined if varying [Ca2+]o could differentially affect facilitation of GABA- or glycine-operated synapses. With 5 mM [Ca2+]o, the frequency of spontaneous GABAergic or glycinergic currents appeared much higher but GABAergic current facilitation was blocked (and replaced by depression), whereas glycinergic currents remained slightly facilitated. [Ca2+]omanipulation thus brought about distinct processes responsible for facilitation of GABAergic or glycinergic transmission. Our data therefore demonstrate an unexpectedly robust, short-term increase in the efficiency of GABAergic synapses that can become at least as effective as glycinergic synapses.
7
Liu, Tao, Tsugumi Fujita, Terumasa Nakatsuka, and Eiichi Kumamoto. "Phospholipase A2 Activation Enhances Inhibitory Synaptic Transmission in Rat Substantia Gelatinosa Neurons." Journal of Neurophysiology 99, no. 3 (March 2008): 1274–84. http://dx.doi.org/10.1152/jn.01292.2007.
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Phospholipase A2 (PLA2) activation enhances glutamatergic excitatory synaptic transmission in substantia gelatinosa (SG) neurons, which play a pivotal role in regulating nociceptive transmission in the spinal cord. By using melittin as a tool to activate PLA2, we examined the effect of PLA2 activation on spontaneous inhibitory postsynaptic currents (sIPSCs) recorded at 0 mV in SG neurons of adult rat spinal cord slices by use of the whole cell patch-clamp technique. Melittin enhanced the frequency and amplitude of GABAergic and glycinergic sIPSCs. The enhancement of GABAergic but not glycinergic transmission was largely depressed by Na+ channel blocker tetrodotoxin or glutamate-receptor antagonists (6-cyano-7-nitroquinoxaline-2,3-dione and/or dl-2-amino-5-phosphonovaleric acid) and also in a Ca2+-free Krebs solution. The effects of melittin on glycinergic sIPSC frequency and amplitude were dose-dependent with an effective concentration of ∼0.7 μM for half-maximal effect and were depressed by PLA2 inhibitor 4-bromophenacyl bromide or aristolochic acid. The melittin-induced enhancement of glycinergic transmission was depressed by lipoxygenase inhibitor nordihydroguaiaretic acid but not cyclooxygenase inhibitor indomethacin. These results indicate that the activation of PLA2 in the SG enhances GABAergic and glycinergic inhibitory transmission in SG neurons. The former action is mediated by glutamate-receptor activation and neuronal activity increase, possibly the facilitatory effect of PLA2 activation on excitatory transmission, whereas the latter action is due to PLA2 and subsequent lipoxygenase activation and is independent of extracellular Ca2+. It is suggested that PLA2 activation in the SG could enhance not only excitatory but also inhibitory transmission, resulting in the modulation of nociception.
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Sebe, Joy Y., Erika D. Eggers, and Albert J. Berger. "Differential Effects of Ethanol on GABAA and Glycine Receptor-Mediated Synaptic Currents in Brain Stem Motoneurons." Journal of Neurophysiology 90, no. 2 (August 2003): 870–75. http://dx.doi.org/10.1152/jn.00119.2003.
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Ethanol potentiates glycinergic synaptic transmission to hypoglossal motoneurons (HMs). This effect on glycinergic transmission changes with postnatal development in that juvenile HMs (P9–13) are more sensitive to ethanol than neonate HMs (P1–3). We have now extended our previous study to investigate ethanol modulation of synaptic GABAA receptors (GABAARs), because both GABA and glycine mediate inhibitory synaptic transmission to brain stem motoneurons. We tested the effects of ethanol on GABAergic and glycinergic miniature inhibitory postsynaptic currents (mIPSCs) recorded from neonate and juvenile rat HMs in an in vitro slice preparation. Bath application of 30 mM ethanol had no significant effect on the GABAergic mIPSC amplitude or frequency recorded at either age. At 100 mM, ethanol significantly decreased the GABAergic mIPSC amplitude recorded from neonate (6 ± 3%, P < 0.05) and juvenile (16 ± 3%, P < 0.01) HMs. The same concentration of ethanol increased the GABAergic mIPSC frequency recorded from neonate (64 ± 17%, P < 0.05) and juvenile (40 ± 15%, n.s.) HMs. In contrast, 100 mM ethanol robustly potentiated glycinergic mIPSC amplitude in neonate (31 ± 3%, P < 0.0001) and juvenile (41 ± 7%, P < 0.001) HMs. These results suggest that glycine receptors are more sensitive to modulation by ethanol than GABAA receptors and that 100 mM ethanol has the opposite effect on GABAAR-mediated currents in juvenile HMs, that is, inhibition rather than enhancement. Further, comparing ethanol's effects on GABAergic mIPSC amplitude and frequency, ethanol modulates GABAergic synaptic transmission to HMs differentially. Presynaptically, ethanol enhances mIPSC frequency while postsynaptically it decreases mIPSC amplitude.
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Oda, Y., S. Charpier, Y. Murayama, C. Suma, and H. Korn. "Long-term potentiation of glycinergic inhibitory synaptic transmission." Journal of Neurophysiology 74, no. 3 (September 1, 1995): 1056–74. http://dx.doi.org/10.1152/jn.1995.74.3.1056.
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1. Tetanizing protocols were used to test whether glycinergic inhibition undergoes long-term plasticity in vivo. For this purpose we studied the inhibition evoked disynaptically in the teleost Mauthner (M) cell by stimulation of the posterior branch of the contralateral VIIIth nerve. The advantage of this experimental design is that the inhibition, which is mediated by identified second-order commissural interneurons, is not contaminated by parallel excitation. 2. The VIIIth-nerve-evoked inhibitory postsynaptic potentials (IPSPs), which are generated at the level of the soma, are depolarizing in Cl(-)-loaded M cells. After VIIIth nerve tetanization, these IPSPs exhibited potentiation lasting > 30 min in 23 of 31 cells. The maximum enhancement measured 5-10 min after the onset of the tetanization averaged 100 +/- 19% (mean +/- SE). In contrast, the non-"tetanized" collateral IPSP induced by antidromic stimulation of the M axon did not increase significantly suggesting synaptic specificity of the potentiation. 3. Single-electrode voltage-clamp studies of Cl(-)-loaded M cells indicated that this plasticity is due to an increased synaptic conductance that occurs without obvious modifications of the kinetics or voltage dependence of the inhibitory postsynaptic currents. 4. The synaptic conductance and its changes during potentiation were quantified by measuring the inhibitory shunt of the antidromic spike while recording with potassium-acetate-filled electrodes. For this purpose the ratio, r', of the inhibitory to resting membrane conductances, was calculated using the expression (V/V')--1, where V and V' are the amplitudes of the control and the test antidromic spikes, respectively. This ratio was called fractional conductance. Measured at the peak of the expected VIIIth-nerve-evoked IPSP, r' increased by 114 +/- 18% (n = 46). Again the collateral inhibitory conductance was not modified. 5. Because there are two synapses in the inhibitory pathway, it became important to determine whether modifications of the second-order inhibitory junctions contribute to the overall potentiation. Several experimental procedures were used for this purpose. 6. The input-output relationship at the inhibitory synapses was determined by comparing the size of the presynaptic volley and r'. The former was recorded intra- or extracellularly as a monophasic positive potential, the so-called extrinsic hyperpolarizing potential, which increases in parallel with the strength of VIIIth nerve stimulation. In 12 experiments where the presynaptic volley was unaffected by the tetanization, suggesting lack of involvement of the first relay, r' nevertheless increased in amplitude by 79 +/- 14%.(ABSTRACT TRUNCATED AT 400 WORDS)
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Liu, Tao, Tsugumi Fujita, and Eiichi Kumamoto. "Acetylcholine and norepinephrine mediate GABAergic but not glycinergic transmission enhancement by melittin in adult rat substantia gelatinosa neurons." Journal of Neurophysiology 106, no. 1 (July 2011): 233–46. http://dx.doi.org/10.1152/jn.00838.2010.
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GABAergic and glycinergic inhibitory synaptic transmissions in substantia gelatinosa (SG; lamina II of Rexed) neurons of the spinal dorsal horn play an important role in regulating nociceptive transmission from the periphery. It has not yet been well known whether each of the inhibitory transmissions plays a distinct role in the regulation. We report an involvement of neurotransmitters in GABAergic but not glycinergic transmission enhancement produced by the PLA2 activator melittin, where the whole-cell patch-clamp technique is applied to the SG neurons of adult rat spinal cord slices. Glycinergic but not GABAergic spontaneous inhibitory postsynaptic current (sIPSC) was increased in frequency and amplitude by melittin in the presence of nicotinic, muscarinic acetylcholine, and α1-adrenergic receptor antagonists (mecamylamine, atropine, and WB-4101, respectively). GABAergic transmission enhancement produced by melittin was unaffected by the 5-hydroxytryptamine 3 receptor and P2X receptor antagonists (ICS-205,930 and pyridoxalphosphate-6-azophenyl-2′,4′-disulphonic acid, respectively). Nicotinic and muscarinic acetylcholine receptor agonists [(−)-nicotine and carbamoylcholine, respectively] and norepinephrine, as well as melittin, increased GABAergic sIPSC frequency and amplitude. A repeated application of (−)-nicotine, carbamoylcholine, and norepinephrine, but not melittin, at an interval of 30 min produced a similar transmission enhancement. These results indicate that melittin produces the release of acetylcholine and norepinephrine, which activate (nicotinic and muscarinic) acetylcholine and α1-adrenergic receptors, respectively, resulting in GABAergic but not glycinergic transmission enhancement in SG neurons. The desensitization of a system leading to the acetylcholine and norepinephrine release is slow in recovery. This distinction in modulation between GABAergic and glycinergic transmissions may play a role in regulating nociceptive transmission.
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Gao, Bao-Xi, Christian Stricker, and Lea Ziskind-Conhaim. "Transition From GABAergic to Glycinergic Synaptic Transmission in Newly Formed Spinal Networks." Journal of Neurophysiology 86, no. 1 (July 1, 2001): 492–502. http://dx.doi.org/10.1152/jn.2001.86.1.492.
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The role of glycinergic and GABAergic systems in mediating spontaneous synaptic transmission in newly formed neural networks was examined in motoneurons in the developing rat spinal cord. Properties of action potential–independent miniature inhibitory postsynaptic currents (mIPSCs) mediated by glycine and GABAA receptors (GlyR and GABAAR) were studied in spinal cord slices of 17- to 18-day-old embryos ( E17–18) and 1- to 3-day-old postnatal rats ( P1–3). mIPSC frequency and amplitude significantly increased after birth, while their decay time decreased. To determine the contribution of glycinergic and GABAergic synapses to those changes, GlyR- and GABAAR-mediated mIPSCs were isolated based on their pharmacological properties. Two populations of pharmacologically distinct mIPSCs were recorded in the presence of glycine or GABAA receptors antagonists: bicuculline-resistant, fast-decaying GlyR-mediated mIPSCs, and strychnine-resistant, slow-decaying GABAAR-mediated mIPSCs. The frequency of GABAAR-mediated mIPSCs was fourfold higher than that of GlyR-mediated mIPSCs at E17–18, indicating that GABAergic synaptic sites were functionally dominant at early stages of neural network formation. Properties of GABAAR-mediated mIPSC amplitude fluctuations changed from primarily unimodal skewed distribution at E17–18 to Gaussian mixtures with two to three discrete components at P1–3. A developmental shift from primarily long-duration GABAergic mIPSCs to short-duration glycinergic mIPSCs was evident after birth, when the frequency of GlyR-mediated mIPSCs increased 10-fold. This finding suggested that either the number of glycinergic synapses or the probability of vesicular glycine release increased during the period studied. The increased frequency of GlyR-mediated mIPSCs was associated with more than a twofold increase in their mean amplitude, and in the number of motoneurons in which mIPSC amplitude fluctuations were best fitted by multi-component Gaussian curves. A third subpopulation of mIPSCs was apparent in the absence of glycine and GABAA receptor antagonists: mIPSCs with both fast and slow decaying components. Based on their dual-component decay time and their suppression by either strychnine or bicuculline, we assumed that these were generated by the activation of co-localized postsynaptic glycine and GABAA receptors. The contribution of mixed glycine-GABA synaptic sites to the generation of mIPSCs did not change after birth. The developmental switch from predominantly long-duration GABAergic inhibitory synaptic currents to short-duration glycinergic currents might serve as a mechanism regulating neuronal excitation in the developing spinal networks.
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Schubert, Timm, Daniel Kerschensteiner, Erika D. Eggers, Thomas Misgeld, Martin Kerschensteiner, Jeff W. Lichtman, Peter D. Lukasiewicz, and Rachel O. L. Wong. "Development of Presynaptic Inhibition Onto Retinal Bipolar Cell Axon Terminals Is Subclass-Specific." Journal of Neurophysiology 100, no. 1 (July 2008): 304–16. http://dx.doi.org/10.1152/jn.90202.2008.
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Synaptic integration is modulated by inhibition onto the dendrites of postsynaptic cells. However, presynaptic inhibition at axonal terminals also plays a critical role in the regulation of neurotransmission. In contrast to the development of inhibitory synapses onto dendrites, GABAergic/glycinergic synaptogenesis onto axon terminals has not been widely studied. Because retinal bipolar cells receive subclass-specific patterns of GABAergic and glycinergic presynaptic inhibition, they are a good model for studying the development of inhibition at axon terminals. Here, using whole cell recording methods and transgenic mice in which subclasses of retinal bipolar cells are labeled, we determined the temporal sequence and patterning of functional GABAergic and glycinergic input onto the major subclasses of bipolar cells. We found that the maturation of GABAergic and glycinergic synapses onto the axons of rod bipolar cells (RBCs), on-cone bipolar cells (on-CBCs) and off-cone bipolar cells (off-CBCs) were temporally distinct: spontaneous chloride-mediated currents are present in RBCs earlier in development compared with on- and off-CBC, and RBCs receive GABAergic and glycinergic input simultaneously, whereas in off-CBCs, glycinergic transmission emerges before GABAergic transmission. Because on-CBCs show little inhibitory activity, GABAergic and glycinergic events could not be pharmacologically distinguished for these bipolar cells. The balance of GABAergic and glycinergic input that is unique to RBCs and off-CBCs is established shortly after the onset of synapse formation and precedes visual experience. Our data suggest that presynaptic modulation of glutamate transmission from bipolar cells matures rapidly and is differentially coordinated for GABAergic and glycinergic synapses onto distinct bipolar cell subclasses.
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Xie (解瑞立), Ruili, and Paul B. Manis. "Glycinergic synaptic transmission in the cochlear nucleus of mice with normal hearing and age-related hearing loss." Journal of Neurophysiology 110, no. 8 (October 15, 2013): 1848–59. http://dx.doi.org/10.1152/jn.00151.2013.
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The principal inhibitory neurotransmitter in the mammalian cochlear nucleus (CN) is glycine. During age-related hearing loss (AHL), glycinergic inhibition becomes weaker in CN. However, it is unclear what aspects of glycinergic transmission are responsible for weaker inhibition with AHL. We examined glycinergic transmission onto bushy cells of the anteroventral CN in normal-hearing CBA/CaJ mice and in DBA/2J mice, a strain that exhibits an early onset AHL. Glycinergic synaptic transmission was examined in brain slices of mice at 10–15 postnatal days old, 20–35 days old, and at 6–7 mo old. Spontaneous inhibitory postsynaptic current (sIPSC) event frequency and amplitude were the same among all three ages in both strains of mice. However, the amplitudes of IPSCs evoked (eIPSC) from stimulating the dorsal CN were smaller, and the failure rate was higher, with increasing age due to decreased quantal content in both mouse strains, independent of hearing status. The coefficient of variation of the eIPSC amplitude also increased with age. The decay time constant (τ) of sIPSCs and eIPSCs were constant in CBA/CaJ mice at all ages, but were significantly slower in DBA/2J mice at postnatal days 20–35, following the onset of AHL, and not at earlier or later ages. Our results suggest that glycinergic inhibition at the synapses onto bushy cells becomes weaker and less reliable with age through changes in release. However, the hearing loss in DBA/2J mice is accompanied by a transiently enhanced inhibition, which could disrupt the balance of excitation and inhibition.
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Lim, Rebecca, Robert J. Callister, and Alan M. Brichta. "An Increase in Glycinergic Quantal Amplitude and Frequency During Early Vestibular Compensation in Mouse." Journal of Neurophysiology 103, no. 1 (January 2010): 16–24. http://dx.doi.org/10.1152/jn.91223.2008.
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The process of vestibular compensation includes both behavioral and neuronal recovery after unilateral loss of peripheral vestibular organs. The mechanisms that underlie this process are poorly understood. Previous research has shown the presence of both γ-aminobutyric acid type A (GABAA) and glycine receptors in the medial vestibular nuclei (MVN). It has been suggested that inhibitory transmission mediated by these receptors may have a role in recovery during vestibular compensation. This study investigated changes in fast inhibitory synaptic transmission of GABAAergic and glycinergic quantal events after unilateral labyrinthectomy (UL) at three different time points. Mice were anesthetized and peripheral vestibular organs were removed from one side of the head. After recovery, transverse brain stem sections (300 μm) were prepared from mice that had undergone UL either 4 hours, 2 days, or 7 days earlier. Our experiments do not show evidence for alterations in synaptic GABAA receptor properties in MVN neurons after UL at any time point investigated. In contrast, during early vestibular compensation (4 hours post UL) there is a significant increase in the glycinergic quantal current amplitude in contralesional MVN neurons compared with control. Our results also show an increase in the frequency of glycinergic quantal events of both ipsi- and contralesional MVN neurons during this early period. We suggest that changes in both pre- and postsynaptic glycine receptor mediated inhibitory synaptic transmission after sensory loss is an important mechanism by which neuronal discharge patterns can be modulated.
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Singer, Joshua H., Edmund M. Talley, Douglas A. Bayliss, and Albert J. Berger. "Development of Glycinergic Synaptic Transmission to Rat Brain Stem Motoneurons." Journal of Neurophysiology 80, no. 5 (November 1, 1998): 2608–20. http://dx.doi.org/10.1152/jn.1998.80.5.2608.
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Singer, Joshua H., Edmund M. Talley, Douglas A. Bayliss, and Albert J. Berger. Development of glycinergic synaptic transmission to rat brain stem motoneurons. J. Neurophysiol. 80: 2608–2620, 1998. Using an in vitro rat brain stem slice preparation, we examined the postnatal changes in glycinergic inhibitory postsynaptic currents (IPSCs) and passive membrane properties that underlie a developmental change in inhibitory postsynaptic potentials (IPSPs) recorded in hypoglossal motoneurons (HMs). Motoneurons were placed in three age groups: neonate (P0–3), intermediate (P5–8), and juvenile (P10–18). During the first two postnatal weeks, the decay time course of both unitary evoked IPSCs [mean decay time constant, τdecay = 17.0 ± 1.6 (SE) ms in neonates and 5.5 ± 0.4 ms in juveniles] and spontaneous miniature IPSCs (τdecay = 14.2 ± 2.4 ms in neonates and 6.3 ± 0.7 ms in juveniles) became faster. As glycine uptake does not influence IPSC time course at any postnatal age, this change most likely results from a developmental alteration in glycine receptor (GlyR) subunit composition. We found that expression of fetal (α2) GlyR subunit mRNA decreased, whereas expression of adult (α1) GlyR subunit mRNA increased postnatally. Single GlyR-channels recorded in outside-out patches excised from neonate motoneurons had longer mean burst durations than those from juveniles (18.3 vs. 11.1 ms). Concurrently, HM input resistance ( R N) and membrane time constant (τm) decreased ( R N from 153 ± 12 MΩ to 63 ± 7 MΩ and τm from 21.5 ± 2.7 ms to 9.1 ± 1.0 ms, neonates and juveniles, respectively), and the time course of unitary evoked IPSPs also became faster (τdecay = 22.4 ± 1.8 and 7.7 ± 0.9 ms, neonates vs. juveniles, respectively). Simulated synaptic currents were used to probe more closely the interaction between IPSC time course and τm, and these simulations demonstrated that IPSP duration was reduced as a consequence of postnatal changes in both the kinetics of the underlying GlyR channel and the membrane properties that transform the IPSC into a postsynaptic potential. Additionally, gramicidin perforated-patch recordings of glycine-evoked currents reveal a postnatal change in reversal potential, which is shifted from −37 to −73 mV during this same period. Glycinergic PSPs are therefore depolarizing and prolonged in neonate HMs and become faster and hyperpolarizing during the first two postnatal weeks.
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Shao, Mei, June C. Hirsch, and Kenna D. Peusner. "Emergence of Action Potential Generation and Synaptic Transmission in Vestibular Nucleus Neurons." Journal of Neurophysiology 96, no. 3 (September 2006): 1215–26. http://dx.doi.org/10.1152/jn.00180.2006.
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Principal cells of the chick tangential nucleus are vestibular nucleus neurons in the hindbrain. Although detailed information is available on the morphogenesis of principal cells and synaptogenesis of primary vestibular fibers, this is the first study of their early functional development, when vestibular terminals emerge at embryonic days 10 and 13 (E10 and E13). At E10, 60% of principal cells generated spikes on depolarization, whereas 50% exhibited excitatory postsynaptic currents (EPSCs) on vestibular-nerve stimulation. The frequency was 0.2 Hz for glutamatergic spontaneous EPSCs (sEPSCs) at −60 mV, and 0.6 Hz for spontaneous inhibitory postsynaptic current (sIPSC) at +10 mV and completely GABAergic. All of these synaptic events were TTX-insensitive, miniature events. At E13, 50% of principal cells generated spikes on depolarization and 82% exhibited EPSCs on vestibular-nerve stimulation. The frequency was 0.7 Hz for sEPSCs at −60 mV, and 0.8 Hz for sIPSCs at +10 mV. Most principal cells had sIPSCs composed of both GABAergic (75%) and glycinergic (25%) events, but a few cells had only GABAergic sIPSCs. TTX decreased the frequency of EPSCs by 12%, and the IPSCs by 17%. In summary, at E10, some principal cells generated immature spikes on depolarization and EPSCs on vestibular-nerve stimulation. At E10, GABAergic events predominated, AMPA events had low frequencies, and glycinergic activity was absent. By E13, glycinergic events first appeared. This data were compared systematically to that obtained from the late-term embryo and hatchling to reveal the long-term sequence of changes in synaptic events and excitability and offer a broader understanding of how the vestibular system is assembled during development.
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Jin, Xiao-Tao, Ningren Cui, Weiwei Zhong, Xin Jin, Zhongying Wu, and Chun Jiang. "Pre- and postsynaptic modulations of hypoglossal motoneurons by α-adrenoceptor activation in wild-type and Mecp2−/Y mice." American Journal of Physiology-Cell Physiology 305, no. 10 (November 15, 2013): C1080—C1090. http://dx.doi.org/10.1152/ajpcell.00109.2013.
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Hypoglossal motoneurons (HNs) control tongue movement and play a role in maintenance of upper airway patency. Defects in these neurons may contribute to the development of sleep apnea and other cranial motor disorders including Rett syndrome (RTT). HNs are modulated by norepinephrine (NE) through α-adrenoceptors. Although postsynaptic mechanisms are known to play a role in this effect, how NE modulates the synaptic transmissions of HNs remains poorly understood. More importantly, the NE system is defective in RTT, while how the defect affects HNs is unknown. Believing that information of NE modulation of HNs may help the understanding of RTT and the design of new therapeutical interventions to motor defects in the disease, we performed these studies in which glycinergic inhibitory postsynaptic currents and intrinsic membrane properties were examined in wild-type and Mecp2 −/Y mice, a mouse of model of RTT. We found that activation of α1-adrenoceptor facilitated glycinergic synaptic transmission and excited HNs. These effects were mediated by both pre- and postsynaptic mechanisms. The latter effect involved an inhibition of barium-sensitive G protein-dependent K+ currents. The pre- and postsynaptic modulations of the HNs by α1-adrenoceptors were not only retained in Mecp2-null mice but also markedly enhanced, which appears to be a compensatory mechanism for the deficiencies in NE and GABAergic synaptic transmission. The existence of the endogenous compensatory mechanism is an encouraging finding, as it may allow therapeutical modalities to alleviate motoneuronal defects in RTT.
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Kumamoto, Eiichi. "Cellular Mechanisms for Antinociception Produced by Oxytocin and Orexins in the Rat Spinal Lamina II—Comparison with Those of Other Endogenous Pain Modulators." Pharmaceuticals 12, no. 3 (September 16, 2019): 136. http://dx.doi.org/10.3390/ph12030136.
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Much evidence indicates that hypothalamus-derived neuropeptides, oxytocin, orexins A and B, inhibit nociceptive transmission in the rat spinal dorsal horn. In order to unveil cellular mechanisms for this antinociception, the effects of the neuropeptides on synaptic transmission were examined in spinal lamina II neurons that play a crucial role in antinociception produced by various analgesics by using the whole-cell patch-clamp technique and adult rat spinal cord slices. Oxytocin had no effect on glutamatergic excitatory transmission while producing a membrane depolarization, γ-aminobutyric acid (GABA)-ergic and glycinergic spontaneous inhibitory transmission enhancement. On the other hand, orexins A and B produced a membrane depolarization and/or a presynaptic spontaneous excitatory transmission enhancement. Like oxytocin, orexin A enhanced both GABAergic and glycinergic transmission, whereas orexin B facilitated glycinergic but not GABAergic transmission. These inhibitory transmission enhancements were due to action potential production. Oxytocin, orexins A and B activities were mediated by oxytocin, orexin-1 and orexin-2 receptors, respectively. This review article will mention cellular mechanisms for antinociception produced by oxytocin, orexins A and B, and discuss similarity and difference in antinociceptive mechanisms among the hypothalamic neuropeptides and other endogenous pain modulators (opioids, nociceptin, adenosine, adenosine 5’-triphosphate (ATP), noradrenaline, serotonin, dopamine, somatostatin, cannabinoids, galanin, substance P, bradykinin, neuropeptide Y and acetylcholine) exhibiting a change in membrane potential, excitatory or inhibitory transmission in the spinal lamina II neurons.
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Du, J. L., and X. L. Yang. "Glycinergic synaptic transmission to bullfrog retinal bipolar cells is input-specific." Neuroscience 113, no. 4 (September 2002): 779–84. http://dx.doi.org/10.1016/s0306-4522(02)00255-5.
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Reymond-Marron, I., M. Raggenbass, and M. Zaninetti. "Vasopressin facilitates glycinergic and GABAergic synaptic transmission in developing hypoglossal motoneurons." European Journal of Neuroscience 21, no. 6 (March 2005): 1601–9. http://dx.doi.org/10.1111/j.1460-9568.2005.03996.x.
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McMenamin, Caitlin A., Laura Anselmi, R. Alberto Travagli, and Kirsteen N. Browning. "Developmental regulation of inhibitory synaptic currents in the dorsal motor nucleus of the vagus in the rat." Journal of Neurophysiology 116, no. 4 (October 1, 2016): 1705–14. http://dx.doi.org/10.1152/jn.00249.2016.
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Prior immunohistochemical studies have demonstrated that at early postnatal time points, central vagal neurons receive both glycinergic and GABAergic inhibitory inputs. Functional studies have demonstrated, however, that adult vagal efferent motoneurons receive only inhibitory GABAergic synaptic inputs, suggesting loss of glycinergic inhibitory neurotransmission during postnatal development. The purpose of the present study was to test the hypothesis that the loss of glycinergic inhibitory synapses occurs in the immediate postnatal period. Whole cell patch-clamp recordings were made from dorsal motor nucleus of the vagus (DMV) neurons from postnatal days 1–30, and the effects of the GABAA receptor antagonist bicuculline (1–10 μM) and the glycine receptor antagonist strychnine (1 μM) on miniature inhibitory postsynaptic current (mIPSC) properties were examined. While the baseline frequency of mIPSCs was not altered by maturation, perfusion with bicuculline either abolished mIPSCs altogether or decreased mIPSC frequency and decay constant in the majority of neurons at all time points. In contrast, while strychnine had no effect on mIPSC frequency, its actions to increase current decay time declined during postnatal maturation. These data suggest that in early postnatal development, DMV neurons receive both GABAergic and glycinergic synaptic inputs. Glycinergic neurotransmission appears to decline by the second postnatal week, and adult neurons receive principally GABAergic inhibitory inputs. Disruption of this developmental switch from GABA-glycine to purely GABAergic transmission in response to early life events may, therefore, lead to adverse consequences in vagal efferent control of visceral functions.
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Fischl, Matthew J., Sonia R. Weimann, Michael G. Kearse, and R. Michael Burger. "Slowly emerging glycinergic transmission enhances inhibition in the sound localization pathway of the avian auditory system." Journal of Neurophysiology 111, no. 3 (February 1, 2014): 565–72. http://dx.doi.org/10.1152/jn.00640.2013.
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Localization of low-frequency acoustic stimuli is processed in dedicated neural pathways where coincidence-detecting neurons compare the arrival time of sound stimuli at the two ears, or interaural time disparity (ITD). ITDs occur in the submillisecond range, and vertebrates have evolved specialized excitatory and inhibitory circuitry to compute these differences. Glycinergic inhibition is a computationally significant and prominent component of the mammalian ITD pathway. However, evidence for glycinergic transmission is limited in birds, where GABAergic inhibition has been thought to be the dominant or exclusive inhibitory transmitter. Indeed, previous work showed that GABA antagonists completely eliminate inhibition in avian nuclei specialized for processing temporal features of sound, nucleus magnocellularis (NM) and nucleus laminaris (NL). However, more recent work shows that glycine is coexpressed with GABA in synaptic terminals apposed to neurons in both nuclei (Coleman WL, Fischl MJ, Weimann SR, Burger RM. J Neurophysiol 105: 2405–2420, 2011; Kuo SP, Bradley LA, Trussell LO. J Neurosci 29: 9625–9634, 2009). Here we show complementary evidence of functional glycine receptor (GlyR) expression in NM and NL. Additionally, we show that glycinergic input can be evoked under particular stimulus conditions. Stimulation at high but physiologically relevant rates evokes a slowly emerging glycinergic response in NM and NL that builds over the course of the stimulus. Glycinergic response magnitude was stimulus rate dependent, representing 18% and 7% of the total inhibitory current in NM and NL, respectively, at the end of the 50-pulse, 200-Hz stimulus. Finally, we show that the glycinergic component is functionally relevant, as its elimination reduced inhibition of discharges evoked by current injection into NM neurons.
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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.
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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.
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Sebe, Joy Y., Johannes F. van Brederode, and Albert J. Berger. "Inhibitory Synaptic Transmission Governs Inspiratory Motoneuron Synchronization." Journal of Neurophysiology 96, no. 1 (July 2006): 391–403. http://dx.doi.org/10.1152/jn.00086.2006.
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Neurons within the intact respiratory network produce bursts of action potentials that cause inspiration or expiration. Within inspiratory bursts, activity is synchronized on a shorter timescale to generate clusters of action potentials that occur in a set frequency range and are called synchronous oscillations. We investigated how GABA and glycine modulate synchronous oscillations and respiratory rhythm during postnatal development. We recorded inspiratory activity from hypoglossal nerves using the in vitro rhythmically active mouse medullary slice preparation from P0–P11 mice. Average oscillation frequency increased with postnatal development, from 17 ± 12 Hz in P0–P6 mice ( n = 15) to 38 ± 7 Hz in P7–P11 mice ( n = 37) ( P < 0.0001). Bath application of GABAA and GlyR antagonists significantly reduced oscillation power in neonates (P0–P6) and juveniles (P7–P10) and increased peak integrated activity in both age groups. To test whether elevating slice excitability is sufficient to reduce oscillation power, Substance P was bath applied alone. Substance P, although increasing peak integrated activity, had no significant effect on oscillation power. Prolonging the time course of GABAergic synaptic currents with zolpidem decreased the median oscillation frequency in P9–P10 mouse slices. These data demonstrate that oscillation frequency increases with postnatal development and that both GABAergic and glycinergic transmission contribute to synchronization of activity. Further, the time course of synaptic GABAergic currents is a determinant of oscillation frequency.
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Venkatesan, Priya, Sunit Baxi, Cory Evans, Robert Neff, Xin Wang, and David Mendelowitz. "Glycinergic Inputs to Cardiac Vagal Neurons in the Nucleus Ambiguus Are Inhibited by Nociceptin and μ-Selective Opioids." Journal of Neurophysiology 90, no. 3 (September 2003): 1581–88. http://dx.doi.org/10.1152/jn.01117.2002.
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Most parasympathetic regulation of heart rate originates from preganglionic cardiac vagal neurons within the nucleus ambiguus. Little is known regarding the modulation of glycinergic transmission to these neurons. However, the presence of μ-opioid receptors and opioid-receptor-like (ORL1) receptors within the ambiguus, together with the presence of endogenous ligands for both receptor types in the same area, suggests opioids may modulate synaptic transmission to cardiac vagal neurons. This study therefore examined the effects of endomorphin-1 and endomorphin-2 (the μ-selective endogenous peptides), DAMGO (a synthetic, μ-selective agonist), and nociceptin (the ORL1-selective endogenous peptide) on spontaneous glycinergic inhibitory postsynaptic currents (IPSCs) in rat cardiac parasympathetic neurons. All four of the opioids used in this study decreased spontaneous IPSCs. At concentrations of 100 μM, the amplitude of the IPSCs was reduced significantly by nociceptin (–56.6%), DAMGO (–46.5%), endomorphin-1 (–45.1%), and endomorphin-2 (–26%). IPSC frequency was also significantly reduced by nociceptin (–61.1%), DAMGO (–69.9%), and endomorphin-1 (–40.8%) but not endomorphin-2. Lower concentrations of nociceptin and DAMGO (10–30 μM) also effectively decreased IPSC amplitude and frequency. The inhibitory effects of DAMGO were blocked by d-Phe-Cys-Tyr-d-Trp-Orn-Thr-Pen-Thr-NH2 (C-TOP; 10 μM), a selective μ-receptor antagonist. Neither nociceptin nor DAMGO inhibited the postsynaptic responses evoked by exogenous application of glycine or affected TTX-insensitive glycinergic mini-IPSCs. These results indicate that μ-selective opioids and nociceptin act on preceding neurons to decrease glycinergic inputs to cardiac vagal neurons in the nucleus ambiguus. The resulting decrease in glycinergic transmission would increase parasympathetic activity to the heart and may be a mechanism by which opioids induce bradycardia.
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Kawa, Kazuyoshi. "Glycine Receptors and Glycinergic Synaptic Transmission in the Deep Cerebellar Nuclei of the Rat: A Patch-Clamp Study." Journal of Neurophysiology 90, no. 5 (November 2003): 3490–500. http://dx.doi.org/10.1152/jn.00447.2003.
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To clarify possible glycinergic transmission in the cerebellum, principal neurons in deep cerebellar nuclei (DCN) of sliced cerebella (200 μm in thickness) from rats (aged 2–14 days) were studied using whole cell patch-clamp techniques. When glycine (100 μM) was applied to the DCN neurons from a “Y tube,” large outward currents were induced (average peak amplitude of about 600 pA at -40 mV). The currents were blocked by strychnine (1 μM) and showed a reversal potential of -62 mV, which was approximately the estimated Cl- equilibrium potential. The dose-response relation of the currents showed an apparent dissociation constant of 170 μM for glycine and Hill coefficient of 1.6. In the presence of 6-cyano-7-nitroquinoziline-2, 3-dione (CNQX), d-(-)-2-amino-5-phosphonovaleric acid (APV) and bicuculline, which antagonize amino-3-hydroxy-5-methyl-isoxazol-propionate (APMA), N-methyl-d-aspartate (NMDA), and GABAA receptors, respectively, postsynaptic currents sensitive to strychnine (1 μM) were induced in DCN neurons by external perfusion of 20 mM K+ saline. Electrical stimulation of surrounding tissues in DCN evoked definite inhibitory postsynaptic currents (IPSCs) in these neurons. The IPSCs had a reversal potential of -62 mV and showed sensitivities to strychnine and tetrodotoxin. Thus this study has revealed that strychnine-sensitive glycine receptors are expressed in neurons of the DCN of rats and that glycinergic transmission mediated by these receptors is functional in these neurons from stages immediately after birth. The glycinergic innervations are presumably supplied by small interneurons located in the DCN.
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van Zundert, Brigitte, Patricio Castro, and Luis G. Aguayo. "Glycinergic and GABAergic synaptic transmission are differentially affected by gephyrin in spinal neurons." Brain Research 1050, no. 1-2 (July 2005): 40–47. http://dx.doi.org/10.1016/j.brainres.2005.05.014.
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Medrihan, L., E. Tantalaki, G. Aramuni, V. Sargsyan, I. Dudanova, M. Missler, and W. Zhang. "Early Defects of GABAergic Synapses in the Brain Stem of a MeCP2 Mouse Model of Rett Syndrome." Journal of Neurophysiology 99, no. 1 (January 2008): 112–21. http://dx.doi.org/10.1152/jn.00826.2007.
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Rett syndrome is a neurodevelopmental disorder caused by mutations in the transcriptional repressor methyl-CpG-binding protein 2 (MeCP2) and represents the leading genetic cause for mental retardation in girls. MeCP2-mutant mice have been generated to study the molecular mechanisms of the disease. It was suggested that an imbalance between excitatory and inhibitory neurotransmission is responsible for the behavioral abnormalities, although it remained largely unclear which synaptic components are affected and how cellular impairments relate to the time course of the disease. Here, we report that MeCP2 KO mice present an imbalance between inhibitory and excitatory synaptic transmission in the ventrolateral medulla already at postnatal day 7. Focusing on the inhibitory synaptic transmission we show that GABAergic, but not glycinergic, synaptic transmission is strongly depressed in MeCP2 KO mice. These alterations are presumably due to both decreased presynaptic γ-aminobutyric acid (GABA) release with reduced levels of the vesicular inhibitory transmitter transporter and reduced levels of postsynaptic GABAA-receptor subunits α2 and α4. Our data indicate that in the MeCP2 −/y mice specific synaptic molecules and signaling pathways are impaired in the brain stem during early postnatal development. These observations mandate the search for more refined diagnostic tools and may provide a rationale for the timing of future therapeutic interventions in Rett patients.
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Thakre, Prajwal P., and Mark C. Bellingham. "Capsaicin causes robust reduction in glycinergic transmission to rat hypoglossal motor neurons via a TRPV1-independent mechanism." Journal of Neurophysiology 121, no. 4 (April 1, 2019): 1535–42. http://dx.doi.org/10.1152/jn.00059.2019.
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The effect of capsaicin on glycinergic synaptic transmission to juvenile rat hypoglossal motor neurons in acute brainstem slices was evaluated in the presence of TTX. Capsaicin caused a robust decrease in miniature IPSC frequency, amplitude, and half-width, showing that this effect is independent of action potential generation. In the presence of capsazepine, a classic TRPV1 antagonist, capsaicin was still able to reduce spontaneous inhibitory postsynaptic current (IPSC) amplitude and frequency. We further investigated whether the effect of capsaicin on glycinergic transmission to hypoglossal motor neurons is pre- or postsynaptic in nature by recording pairs of evoked IPSCs. Interestingly, capsaicin also reduced evoked IPSC amplitude without affecting paired-pulse ratio, indicating a postsynaptic mechanism of action. Significant reduction was also observed in evoked IPSC half-width, rise time, and decay tau. We also show that capsaicin does not have any effect on either transient (It) or sustained (Is) potassium currents. Finally, we also show that the hyperpolarization-activated cationic current (Ih) also remains unchanged after capsaicin application. NEW & NOTEWORTHY Capsaicin reduces the amplitude of quantal and evoked glycinergic inhibitory neurotransmission to brainstem motor neurons without altering activity-dependent transmitter release. This effect of capsaicin is not due to activation of TRPV1 receptors, as it is not blocked by capsazepine, a TRPV1 receptor antagonist. Capsaicin does not alter voltage-dependent potassium current or the hyperpolarization-activated cationic current in brainstem motor neurons.
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Nakamura, Shiro, Tomio Inoue, Kan Nakajima, Masayuki Moritani, Kiyomi Nakayama, Kenichi Tokita, Atsushi Yoshida, and Kohtaro Maki. "Synaptic Transmission From the Supratrigeminal Region to Jaw-Closing and Jaw-Opening Motoneurons in Developing Rats." Journal of Neurophysiology 100, no. 4 (October 2008): 1885–96. http://dx.doi.org/10.1152/jn.01145.2007.
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The supratrigeminal region (SupV) receives abundant orofacial sensory inputs and descending inputs from the cortical masticatory area and contains premotor neurons that target the trigeminal motor nucleus (MoV). Thus it is possible that the SupV is involved in controlling jaw muscle activity via sensory inputs during mastication. We used voltage-sensitive dye, laser photostimulation, patch-clamp recordings, and intracellular biocytin labeling to investigate synaptic transmission from the SupV to jaw-closing and jaw-opening motoneurons in the MoV in brain stem slice preparations from developing rats. Electrical stimulation of the SupV evoked optical responses in the MoV. An antidromic optical response was evoked in the SupV by MoV stimulation, whereas synaptic transmission was suppressed by substitution of external Ca2+ with Mn2+. Photostimulation of the SupV with caged glutamate evoked rapid inward currents in the trigeminal motoneurons. Gramicidin-perforated and whole cell patch-clamp recordings from masseter motoneurons (MMNs) and digastric motoneurons (DMNs) revealed that glycinergic and GABAergic postsynaptic responses evoked in MMNs and DMNs by SupV stimulation were excitatory in P1–P4 neonatal rats and inhibitory in P9–P12 juvenile rats, whereas glutamatergic postsynaptic responses evoked by SupV stimulation were excitatory in both neonates and juveniles. Furthermore, the axons of biocytin-labeled SupV neurons that were antidromically activated by MoV stimulation terminated in the MoV. Our results suggest that inputs from the SupV excite MMNs and DMNs through activation of glutamate, glycine, and GABAA receptors in neonates, whereas glycinergic and GABAergic inputs from the SupV inhibit MMNs and DMNs in juveniles.
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Camp, Aaron J., Robert J. Callister, and Alan M. Brichta. "Inhibitory Synaptic Transmission Differs in Mouse Type A and B Medial Vestibular Nucleus Neurons In Vitro." Journal of Neurophysiology 95, no. 5 (May 2006): 3208–18. http://dx.doi.org/10.1152/jn.01001.2005.
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Fast inhibitory synaptic transmission in the medial vestibular nucleus (MVN) is mediated by GABAA receptors (GABAARs) and glycine receptors (GlyRs). To assess their relative contribution to inhibition in the MVN, we recorded miniature inhibitory postsynaptic currents (mIPSCs) in physiologically characterized type A and type B MVN neurons. Transverse brain stem slices were prepared from mice (3–8 wk old), and whole cell patch-clamp recordings were obtained from visualized MVN neurons (CsCl internal; Vm = –70 mV; 23°C). In 81 MVN neurons, 69% received exclusively GABAAergic inputs, 6% exclusively glycinergic inputs, and 25% received both types of mIPSCs. The mean amplitude of GABAAR-mediated mIPSCs was smaller than those mediated by GlyRs (22.6 ± 1.8 vs. 35.3 ± 5.3 pA). The rise time and decay time constants of GABAAR- versus GlyR-mediated mIPSCs were slower (1.3 ± 0.1 vs. 0.9 ± 0.1 ms and 10.5 ± 0.3 vs. 4.7 ± 0.3 ms, respectively). Comparison of type A ( n = 20) and type B ( n = 32) neurons showed that type A neurons received almost exclusively GABAAergic inhibitory inputs, whereas type B neurons received GABAAergic inputs, glycinergic inputs, or both. Intracellular labeling in a subset of MVN neurons showed that morphology was not related to a MVN neuron's inhibitory profile ( n = 15), or whether it was classified as type A or B ( n = 29). Together, these findings indicate that both GABA and glycine contribute to inhibitory synaptic processing in MVN neurons, although GABA dominates and there is a difference in the distribution of GABAA and Gly receptors between type A and type B MVN neurons.
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Kandler, K., and E. Friauf. "Development of glycinergic and glutamatergic synaptic transmission in the auditory brainstem of perinatal rats." Journal of Neuroscience 15, no. 10 (October 1, 1995): 6890–904. http://dx.doi.org/10.1523/jneurosci.15-10-06890.1995.
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Li, Chun-Yan, Hai-Bo Shi, Jian Wang, Hai-Bo Ye, Ning-ying Song, and Shan-Kai Yin. "Bilirubin facilitates depolarizing GABA/glycinergic synaptic transmission in the ventral cochlear nucleus of rats." European Journal of Pharmacology 660, no. 2-3 (June 2011): 310–17. http://dx.doi.org/10.1016/j.ejphar.2011.03.017.
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St.-John, Walter M., Ilya A. Rybak, and Julian F. R. Paton. "Potential switch from eupnea to fictive gasping after blockade of glycine transmission and potassium channels." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 283, no. 3 (September 1, 2002): R721—R731. http://dx.doi.org/10.1152/ajpregu.00004.2002.
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This study evaluated possible neuronal mechanisms responsible for the transition from normal breathing (eupnea) to gasping. We hypothesized that a blockade of both inhibitory glycinergic synaptic transmission and potassium channels, combined with an increase in extracellular concentration of potassium, would induce a switch from an eupneic respiratory pattern to gasping. Efferent activities of the phrenic, vagal, and hypoglossal nerves were recorded during eupnea and ischemia-induced gasping in a perfused in situ preparation of the juvenile rat (4–6 wk of age). To block potassium channels, 4-aminopyridine (4-AP, 1–10 μM) was administered. Strychnine (0.2–0.6 μM) was used to block glycinergic neurotransmission. After administrations of 4-AP, excess extracellular potassium (10.25–17.25 mM), and strychnine, the incrementing pattern of eupneic phrenic activity was altered to a decrementing discharge. Hypoglossal and vagal activities became concentrated to the period of the phrenic burst with expiratory activity being reduced or eliminated. These changes in neural activities were similar to those in ischemia-induced gasping. Results are consistent with the concept that the elicitation of gasping represents a switch from a network-based rhythmogenesis for eupnea to a pacemaker-driven mechanism.
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Lu, Van B., William F. Colmers, and Peter A. Smith. "Long-term actions of BDNF on inhibitory synaptic transmission in identified neurons of the rat substantia gelatinosa." Journal of Neurophysiology 108, no. 2 (July 15, 2012): 441–52. http://dx.doi.org/10.1152/jn.00457.2011.
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Peripheral nerve injury promotes the release of brain-derived neurotrophic factor (BDNF) from spinal microglial cells and primary afferent terminals. This induces an increase in dorsal horn excitability that contributes to “central sensitization” and to the onset of neuropathic pain. Although it is accepted that impairment of GABAergic and/or glycinergic inhibition contributes to this process, certain lines of evidence suggest that GABA release in the dorsal horn may increase after nerve injury. To resolve these contradictory findings, we exposed rat spinal cord neurons in defined-medium organotypic culture to 200 ng/ml BDNF for 6 days to mimic the change in spinal BDNF levels that accompanies peripheral nerve injury. Morphological and electrophysiological criteria and glutamic acid decarboxylase (GAD) immunohistochemistry were used to distinguish putative inhibitory tonic-islet-central neurons from putative excitatory delay-radial neurons. Whole cell recording in the presence of 1 μM tetrodotoxin showed that BDNF increased the amplitude of GABAergic and glycinergic miniature inhibitory postsynaptic currents (mIPSCs) in both cell types. It also increased the amplitude and frequency of spontaneous, action potential-dependent IPSCs (sIPSCs) in putative excitatory neurons. By contrast, BDNF reduced sIPSC amplitude in inhibitory neurons but frequency was unchanged. This increase in inhibitory drive to excitatory neurons and decreased inhibitory drive to inhibitory neurons seems inconsistent with the observation that BDNF increases overall dorsal horn excitability. One of several explanations for this discrepancy is that the action of BDNF in the substantia gelatinosa is dominated by previously documented increases in excitatory synaptic transmission rather than by impediment of inhibitory transmission.
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van Zundert, Brigitte, Francisco J. Alvarez, Gonzalo E. Yevenes, Juan G. Cárcamo, Juan Carlos Vera, and Luis G. Aguayo. "Glycine Receptors Involved in Synaptic Transmission Are Selectively Regulated by the Cytoskeleton in Mouse Spinal Neurons." Journal of Neurophysiology 87, no. 1 (January 1, 2002): 640–44. http://dx.doi.org/10.1152/jn.00455.2001.
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Using whole cell patch-clamp recordings, we examined the effect of colchicine, a microtubule disrupter, on the properties of glycine receptors (GlyRs) in cultured spinal cord neurons. Confocal microscopy revealed that colchicine treatment effectively altered microtubule bundles and neuronal morphology. Application of colchicine via the culture media or the patch-pipette, however, did not affect the whole cell current rundown (73 ± 6% of control after 1 h), the sensitivity of the GlyR to glycine (EC50 = 29 ± 1 μM), or strychnine inhibition (47 ± 5% of control after 100 nM strychnine). On the other hand, colchicine dialyzed for 25 min via the patch pipette selectively reduced the quantal amplitude of spontaneous glycinergic miniature inhibitory postsynaptic currents (mIPSCs) to 68 ± 5% of control. This effect was specific for GlyRs since synaptic events mediated by α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and GABAA receptors were unchanged. In conclusion, this study indicates that microtubules can regulate the function of GlyRs involved in inhibitory synaptic transmission.
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Cuevas, Magdalena E., Mónica A. Carrasco, Yuly Fuentes, Patricio Castro, Francisco Nualart, Jorge Roa, and Luis G. Aguayo. "The presence of glia stimulates the appearance of glycinergic synaptic transmission in spinal cord neurons." Molecular and Cellular Neuroscience 28, no. 4 (April 2005): 770–78. http://dx.doi.org/10.1016/j.mcn.2005.01.001.
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Apostolides, Pierre F., and Laurence O. Trussell. "Chemical synaptic transmission onto superficial stellate cells of the mouse dorsal cochlear nucleus." Journal of Neurophysiology 111, no. 9 (May 1, 2014): 1812–22. http://dx.doi.org/10.1152/jn.00821.2013.
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The dorsal cochlear nucleus (DCN) is a cerebellum-like auditory brain stem region whose functions include sound localization and multisensory integration. Although previous in vivo studies have shown that glycinergic and GABAergic inhibition regulate the activity of several DCN cell types in response to sensory stimuli, data regarding the synaptic inputs onto DCN inhibitory interneurons remain limited. Using acute DCN slices from mice, we examined the properties of excitatory and inhibitory synapses onto the superficial stellate cell, a poorly understood cell type that provides inhibition to DCN output neurons (fusiform cells) as well as to local inhibitory interneurons (cartwheel cells). Excitatory synapses onto stellate cells activated both NMDA receptors and fast-gating, Ca2+-permeable AMPA receptors. Inhibition onto superficial stellate cells was mediated by glycine and GABAA receptors with different temporal kinetics. Paired recordings revealed that superficial stellate cells make reciprocal synapses and autapses, with a connection probability of ∼18–20%. Unexpectedly, superficial stellate cells co-released both glycine and GABA, suggesting that co-transmission may play a role in fine-tuning the duration of inhibitory transmission.
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Ziskind-Conhaim, Lea, Linying Wu, and Eric P. Wiesner. "Persistent Sodium Current Contributes to Induced Voltage Oscillations in Locomotor-Related Hb9 Interneurons in the Mouse Spinal Cord." Journal of Neurophysiology 100, no. 4 (October 2008): 2254–64. http://dx.doi.org/10.1152/jn.90437.2008.
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Neurochemically induced membrane voltage oscillations and firing episodes in spinal excitatory interneurons expressing the HB9 protein (Hb9 INs) are synchronous with locomotor-like rhythmic motor outputs, suggesting that they contribute to the excitatory drive of motoneurons during locomotion. Similar to central pattern generator neurons in other systems, Hb9 INs are interconnected via electrical coupling, and their rhythmic activity does not depend on fast glutamatergic synaptic transmission. The primary objective of this study was to determine the contribution of fast excitatory and inhibitory synaptic transmission and subthreshold voltage-dependent currents to the induced membrane oscillations in Hb9 INs in the postnatal mouse spinal cord. The non- N-methyl-d-aspartate receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) reduced the amplitude of voltage oscillations but did not alter their frequency. CNQX suppressed rhythmic motor activity. Blocking glycine and GABAA receptor-mediated inhibitory synapses as well as cholinergic transmission did not change the properties of CNQX-resistant membrane oscillations. However, disinhibition triggered new episodes of slow motor bursting that were not correlated with induced locomotor-like rhythms in Hb9 INs. Our observations indicated that fast excitatory and inhibitory synaptic inputs did not control the frequency of induced rhythmic activity in Hb9 INs. We next examined the contribution of persistent sodium current ( INaP) to subthreshold membrane oscillations in the absence of primary glutamatergic, GABAergic and glycinergic synaptic drive to Hb9 INs. Low concentrations of riluzole that blocked the slow-inactivating component of sodium current gradually suppressed the amplitude and reduced the frequency of voltage oscillations. Our finding that INaP regulates locomotor-related rhythmic activity in Hb9 INs independently of primary synaptic transmission supports the concept that these neurons constitute an integral component of the rhythmogenic locomotor network in the mouse spinal cord.
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Graham, B. A. "Distinct Physiological Mechanisms Underlie Altered Glycinergic Synaptic Transmission in the Murine Mutants spastic, spasmodic, and oscillator." Journal of Neuroscience 26, no. 18 (May 3, 2006): 4880–90. http://dx.doi.org/10.1523/jneurosci.3991-05.2006.
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Jiang, Chang-Yu, Tsugumi Fujita, and Eiichi Kumamoto. "Synaptic modulation and inward current produced by oxytocin in substantia gelatinosa neurons of adult rat spinal cord slices." Journal of Neurophysiology 111, no. 5 (March 1, 2014): 991–1007. http://dx.doi.org/10.1152/jn.00609.2013.
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Cellular mechanisms for antinociception produced by oxytocin in the spinal dorsal horn have not yet been investigated thoroughly. We examined how oxytocin affects synaptic transmission in substantia gelatinosa neurons, which play a pivotal role in regulating nociceptive transmission, by applying the whole-cell patch-clamp technique to the substantia gelatinosa neurons of adult rat spinal cord slices. Bath-applied oxytocin did not affect glutamatergic spontaneous, monosynaptically-evoked primary-afferent Aδ-fiber and C-fiber excitatory transmissions. On the other hand, oxytocin produced an inward current at −70 mV and enhanced GABAergic and glycinergic spontaneous inhibitory transmissions. These activities were repeated with a slow recovery from desensitization, concentration-dependent and mimicked by oxytocin-receptor agonist. The oxytocin current was inhibited by oxytocin-receptor antagonist, intracellular GDPβS, U-73122, 2-aminoethoxydiphenyl borate, but not dantrolene, chelerythrine, dibutyryl cyclic-AMP, CNQX, Ca2+-free and tetrodotoxin, while the spontaneous inhibitory transmission enhancements were depressed by tetrodotoxin. Current-voltage relation for the oxytocin current reversed at negative potentials more than the equilibrium potential for K+, or around 0 mV. The oxytocin current was depressed in high-K+, low-Na+ or Ba2+-containing solution. Vasopressin V1A-receptor antagonist inhibited the oxytocin current, but there was no correlation in amplitude between a vasopressin-receptor agonist [Arg8]vasopressin and oxytocin responses. It is concluded that oxytocin produces a membrane depolarization mediated by oxytocin but not vasopressin-V1A receptors, which increases neuronal activity, resulting in the enhancement of inhibitory transmission, a possible mechanism for antinociception. This depolarization is due to a change in membrane permeabilities to K+ and/or Na+, which is possibly mediated by phospholipase C and inositol 1,4,5-triphosphate-induced Ca2+-release.
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Kanjhan, Refik, Peter G. Noakes, and Mark C. Bellingham. "Emerging Roles of Filopodia and Dendritic Spines in Motoneuron Plasticity during Development and Disease." Neural Plasticity 2016 (2016): 1–31. http://dx.doi.org/10.1155/2016/3423267.
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Motoneurons develop extensive dendritic trees for receiving excitatory and inhibitory synaptic inputs to perform a variety of complex motor tasks. At birth, the somatodendritic domains of mouse hypoglossal and lumbar motoneurons have dense filopodia and spines. Consistent with Vaughn’s synaptotropic hypothesis, we propose a developmental unified-hybrid model implicating filopodia in motoneuron spinogenesis/synaptogenesis and dendritic growth and branching critical for circuit formation and synaptic plasticity at embryonic/prenatal/neonatal period. Filopodia density decreases and spine density initially increases until postnatal day 15 (P15) and then decreases by P30. Spine distribution shifts towards the distal dendrites, and spines become shorter (stubby), coinciding with decreases in frequency and increases in amplitude of excitatory postsynaptic currents with maturation. In transgenic mice, either overexpressing the mutated human Cu/Zn-superoxide dismutase (hSOD1G93A) gene or deficient in GABAergic/glycinergic synaptic transmission (gephyrin, GAD-67, or VGAT gene knockout), hypoglossal motoneurons develop excitatory glutamatergic synaptic hyperactivity. Functional synaptic hyperactivity is associated with increased dendritic growth, branching, and increased spine and filopodia density, involving actin-based cytoskeletal and structural remodelling. Energy-dependent ionic pumps that maintain intracellular sodium/calcium homeostasis are chronically challenged by activity and selectively overwhelmed by hyperactivity which eventually causes sustained membrane depolarization leading to excitotoxicity, activating microglia to phagocytose degenerating neurons under neuropathological conditions.
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Wollman, Lila Buls, Richard B. Levine, and Ralph F. Fregosi. "Developmental nicotine exposure alters glycinergic neurotransmission to hypoglossal motoneurons in neonatal rats." Journal of Neurophysiology 120, no. 3 (September 1, 2018): 1135–42. http://dx.doi.org/10.1152/jn.00600.2017.
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We tested the hypothesis that nicotine exposure in utero and after birth [developmental nicotine exposure (DNE)] disrupts development of glycinergic synaptic transmission to hypoglossal motoneurons (XIIMNs). Glycinergic spontaneous and miniature inhibitory postsynaptic currents (sIPSC/mIPSC) were recorded from XIIMNs in brain stem slices from 1- to 5-day-old rat pups of either sex, under baseline conditions and following stimulation of nicotinic acetylcholine (ACh) receptors with nicotine (i.e., an acute nicotine challenge). Under baseline conditions, there were no significant effects of DNE on the amplitude or frequency of either sIPSCs or mIPSCs. In addition, DNE did not alter the magnitude of the whole cell current evoked by bath application of glycine, consistent with an absence of change in postsynaptic glycine-mediated conductance. An acute nicotine challenge (bath application of 0.5 μM nicotine) increased sIPSC frequency in the DNE cells, but not control cells. In contrast, nicotine challenge did not change mIPSC frequency in either control or DNE cells. In addition, there were no significant changes in the amplitude of either sIPSCs or mIPSCs in response to nicotine challenge. The increased frequency of sIPSCs in response to an acute nicotine challenge in DNE cells reflects an enhancement of action potential-mediated input from glycinergic interneurons to hypoglossal motoneurons. This could lead to more intense inhibition of hypoglossal motoneurons in response to exogenous nicotine or endogenous ACh. The former would occur with smoking or e-cigarette use while the latter occurs with changes in sleep state and with hypercapnia. NEW & NOTEWORTHY Here we show that perinatal nicotine exposure does not impact baseline glycinergic neurotransmission to hypoglossal motoneurons but enhances glycinergic inputs to hypoglossal motoneurons in response to activation of nicotinic acetylcholine (ACh) receptors with acute nicotine. Given that ACh is the endogenous ligand for nicotinic ACh receptors, the latter reveals a potential mechanism whereby perinatal nicotine exposure alters motor function under conditions where ACh release increases, such as the transition from non-rapid-eye movement to rapid-eye movement sleep, and during hypercapnia.
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Baba, Hiroshi, Koki Shimoji, and Megumu Yoshimura. "Norepinephrine Facilitates Inhibitory Transmission in Substantia Gelatinosa of Adult Rat Spinal Cord (Part 1)." Anesthesiology 92, no. 2 (February 1, 2000): 473. http://dx.doi.org/10.1097/00000542-200002000-00030.
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Background The activation of descending norepinephrine-containing fibers from the brain stem inhibits nociceptive transmission at the spinal level. How these descending noradrenergic pathways exert the analgesic effect is not understood fully. Membrane hyperpolarization of substantia gelatinosa (Rexed lamina II) neurons by the activation of alpha2 receptors may account for depression of pain transmission. In addition, it is possible that norepinephrine affects transmitter release in the substantia gelatinosa. Methods Adult male Sprague-Dawley rats (9-10 weeks of age, 250-300 g) were used in this study. Transverse spinal cord slices were cut from the isolated lumbar cord. The blind whole-cell patch-clamp technique was used to record from neurons. The effects of norepinephrine on the frequency and amplitude of miniature excitatory and inhibitory postsynaptic currents were evaluated. Results In the majority of substantia gelatinosa neurons tested, norepinephrine (10-100 microM) dose-dependently increased the frequency of gamma-aminobutyric acid (GABA)ergic and glycinergic miniature inhibitory postsynaptic currents; miniature excitatory postsynaptic currents were unaffected. This augmentation was mimicked by an alpha1-receptor agonist, phenylephrine (10-60 microM), and inhibited by alpha1-receptor antagonists prazosin (0.5 microM) and 2-(2,6-dimethoxyphenoxyethyl) amino-methyl-1,4-benzodioxane (0.5 microM). Neither postsynaptic responsiveness to exogenously applied GABA and glycine nor the kinetics of GABAergic and glycinergic inhibitory postsynaptic currents were affected by norepinephrine. Conclusion These results suggest that norepinephrine enhances inhibitory synaptic transmission in the substantia gelatinosa through activation of presynaptic alpha1 receptors, thus providing a mechanism underlying the clinical use of alpha1 agonists with local anesthetics in spinal anesthesia.
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Sadlaoud, K., S. Tazerart, C. Brocard, C. Jean-Xavier, P. Portalier, F. Brocard, L. Vinay, and H. Bras. "Differential Plasticity of the GABAergic and Glycinergic Synaptic Transmission to Rat Lumbar Motoneurons after Spinal Cord Injury." Journal of Neuroscience 30, no. 9 (March 3, 2010): 3358–69. http://dx.doi.org/10.1523/jneurosci.6310-09.2010.
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Noguchi, Tsuyoshi, Shiro Nakamura, Kiyomi Nakayama, Ayako Mochizuki, Masanori Dantsuji, Yoshiaki Ihara, Koji Takahashi, and Tomio Inoue. "Developmental changes in GABAergic and glycinergic synaptic transmission to rat motoneurons innervating jaw-closing and jaw-opening muscles." Brain Research 1777 (February 2022): 147753. http://dx.doi.org/10.1016/j.brainres.2021.147753.
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Yamada, Makiko Hardy, Koichi Nishikawa, Kazuhiro Kubo, Yuchio Yanagawa, and Shigeru Saito. "Impaired Glycinergic Synaptic Transmission and Enhanced Inflammatory Pain in Mice with Reduced Expression of Vesicular GABA Transporter (VGAT)." Molecular Pharmacology 81, no. 4 (January 24, 2012): 610–19. http://dx.doi.org/10.1124/mol.111.076083.
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Yin, Xin-Lu, Min Liang, Hai-Bo Shi, Lu-Yang Wang, Chun-Yan Li, and Shan-Kai Yin. "The role of gamma-aminobutyric acid/glycinergic synaptic transmission in mediating bilirubin-induced hyperexcitation in developing auditory neurons." Toxicology Letters 240, no. 1 (January 2016): 1–9. http://dx.doi.org/10.1016/j.toxlet.2015.10.008.
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Umemiya, Masashi, and Albert J. Berger. "Activation of adenosine A1 and A2 receptors differentially modulates calcium channels and glycinergic synaptic transmission in rat brainstem." Neuron 13, no. 6 (December 1994): 1439–46. http://dx.doi.org/10.1016/0896-6273(94)90429-4.
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Shao, Xuesi M., and Jack L. Feldman. "Respiratory Rhythm Generation and Synaptic Inhibition of Expiratory Neurons in Pre-Bötzinger Complex: Differential Roles of Glycinergic and GABAergic Neural Transmission." Journal of Neurophysiology 77, no. 4 (April 1, 1997): 1853–60. http://dx.doi.org/10.1152/jn.1997.77.4.1853.
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Shao, Xuesi M. and Jack L. Feldman. Respiratory rhythm generation and synaptic inhibition of expiratory neurons in pre-Bötzinger complex: differential roles of glycinergic and GABAergic neural transmission. J. Neurophysiol. 77: 1853–1860, 1997. A key distinction between neural pacemaker and conventional network models for the generation of breathing rhythm in mammals is whether phasic reciprocal inhibitory interactions between inspiratory and expiratory neurons are required. In medullary slices from neonatal rats generating respiratory-related rhythm, we measured the phasic inhibitory inputs to expiratory neurons with the use of whole cell patch clamp in the hypothesized rhythm generation site, the pre-Bötzinger complex (pre-BötC). Expiratory neurons, which generate tonic impulse activity during the expiratory period, exhibited inhibitory postsynaptic potentials (IPSPs) synchronized to the periodic inspiratory bursts of the hypoglossal nerve root (XIIn). Bath application of the glycine receptor antagonist strychnine (STR; 5–10 μM) reversibly blocked these inspiratory-phase IPSPs, whereas the γ-aminobutyric acid-A (GABAA) receptor antagonist bicuculline (BIC; 10–100 μM) had no effect on these IPSPs. Replacing the control in vitro bathing solution with a Cl−-free solution also abolished these IPSPs. Respiratory-related rhythmic activity was not abolished when inspiratory-phase IPSPs were blocked. The frequency and strength of XIIn rhythmic activity increased and seizurelike activity was produced when either STR, BIC, or Cl−-free solution was applied. Inspiratory-phase IPSPs were stable after establishment of whole cell patch conditions (patch pipettes contained 7 mM Cl−). Under voltage clamp, the reversal potential of inspiratory-phase inhibitory postsynaptic currents (IPSCs) was −75 mV. The current-voltage ( I- V) curve for IPSCs shifted to the right when extracellular Cl− concentration was reduced by 50% (70 mM) and the reversal potential was reduced to −60 mV, close to the new Cl− Nernst potential. In tetrodotoxin (0.5 μM) under voltage clamp (holding potential = −45 mV), local application of glycine (1 mM) over pre-BötC induced an outward current and an increase in membrane conductance in expiratory neurons. The effect was blocked by bath application of STR (0.8–1 μM). Local application of the GABAA receptor agonist 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol (THIP, 1 mM) induced an outward current and an increase in membrane conductance that was blocked by BIC (10–100 mM). Under voltage clamp (holding potential = −45 mV), we analyzed spontaneous IPSCs during expiration in expiratory neurons. Bath application of BIC (10 μM) reduced the IPSC frequency (from 2.2 to 0.3 per s), whereas the inspiratory-phase IPSCs did not change. Bath application of STR (8–10 μM) abolished both IPSCs. These results indicate that 1) reciprocal inhibition of expiratory neurons is glycinergic and mediated by a glycine-activated Cl− channel that is not required for respiratory-related rhythm generation in neonatal rat medullary slices; 2) endogenous GABA and glycine modulate the excitability of respiratory neurons and affect respiratory pattern in the slice preparation; 3) both glycine and GABAA receptors are found on pre-BötC expiratory neurons, and these receptors are sensitive to STR and BIC, respectively; 4) glycine and GABAA inhibitory mechanisms play different functional roles in expiratory neurons: both glycine and GABAA receptors modulate neuronal excitability, whereas glycinergic transmission alone is responsible for reciprocal inhibition; and 5) intracellular Cl− concentration in these neonatal expiratory neurons is similar to that in adults.