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Charvet, Christine J., Goran Šimić, Ivica Kostović, Vinka Knezović, Mario Vukšić, Mirjana Babić Leko, Emi Takahashi, Chet C. Sherwood, Marnin D. Wolfe, and Barbara L. Finlay. "Coevolution in the timing of GABAergic and pyramidal neuron maturation in primates." Proceedings of the Royal Society B: Biological Sciences 284, no. 1861 (August 30, 2017): 20171169. http://dx.doi.org/10.1098/rspb.2017.1169.
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The cortex of primates is relatively expanded compared with many other mammals, yet little is known about what developmental processes account for the expansion of cortical subtype numbers in primates, including humans. We asked whether GABAergic and pyramidal neuron production occurs for longer than expected in primates than in mice in a sample of 86 developing primate and rodent brains. We use high-resolution structural, diffusion MR scans and histological material to compare the timing of the ganglionic eminences (GE) and cortical proliferative pool (CPP) maturation between humans, macaques, rats, and mice. We also compare the timing of post-neurogenetic maturation of GABAergic and pyramidal neurons in primates (i.e. humans, macaques) relative to rats and mice to identify whether delays in neurogenesis are concomitant with delayed post-neurogenetic maturation. We found that the growth of the GE and CPP are both selectively delayed compared with other events in primates. By contrast, the timing of post-neurogenetic GABAergic and pyramidal events (e.g. synaptogenesis) are predictable from the timing of other events in primates and in studied rodents. The extended duration of GABAergic and pyramidal neuron production is associated with the amplification of GABAerigc and pyramidal neuron numbers in the human and non-human primate cortex.
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Crawley, Jacqueline N. "GABAergic Antidepressants." Contemporary Psychology: A Journal of Reviews 32, no. 10 (October 1987): 876–77. http://dx.doi.org/10.1037/026430.
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MINCHIN, M., A. WHITE, and K. LLOYD. "GABAERGIC ANTIDEPRESSANTS." Behavioural Pharmacology 3, Supplement (April 1992): 3. http://dx.doi.org/10.1097/00008877-199204001-00001.
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Gottlieb, David I. "GABAergic Neurons." Scientific American 258, no. 2 (February 1988): 82–89. http://dx.doi.org/10.1038/scientificamerican0288-82.
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Cristofolini, Michela, Roberto De Luca, Anne Venner, Loris Ferrari, Kevin Grace, Patrick Fuller, and Elda Arrigoni. "074 Basal Forebrain GABAergic Neurons Promote Arousal by Disinhibiting the Orexin Neurons via Local GABAergic Interneurons." Sleep 44, Supplement_2 (May 1, 2021): A31. http://dx.doi.org/10.1093/sleep/zsab072.073.
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Abstract Introduction Optogenetic and chemogenetic studies have shown that activation of basal forebrain (BF) GABAergic neurons rapidly wakes up mice from non-REM (NREM) sleep. These wake-promoting responses have been attributed to BF GABAergic neurons projecting to the cerebral cortex and more specifically to the inhibition of cortical fast-spiking interneurons. Tracing studies have however found that BF GABAergic neurons also densely innervate the lateral hypothalamus (LH) perifornical area, although the role of this pathway in behavioral state control remains mostly unexplored. Methods We conducted in vivo and in vitro optogenetic studies. We selectively expressed channelrhodopsin-2 (ChR2) in BF GABAergic neurons by injecting a cre-dependent viral vector encoding for ChR2 into the BF of VGAT-cre mice. We photostimulated the BF GABAergic input to the LH with optical fibers placed into the LH of EEG instrumented mice. For in vitro recordings we expressed ChR2 in BF GABAergic neurons and we fluorescently labeled orexin or LH GABAergic neurons. We recorded in brain slices from identified orexin neurons or GABA neurons while photostimulating the BF GABAergic input. Results Optogenetic stimulation of the BF GABAergic fibers in the LH produced rapid arousals from NREM sleep. The same stimulation however did not wake up the mice if they were in REM sleep. We conducted additional studies in brain slices to identify the postsynaptic neurons in the LH targeted by the BF GABAergic input. We found that while optogenetic stimulation of the BF GABAergic input did not produce opto-evoked synaptic responses in the orexin neurons, it produced short-latency opto-evoked inhibitory postsynaptic currents (IPSCs) in LH GABAergic neurons. These opto-evoked IPSCs were GABAA receptor-mediated and were maintained in tetrodotoxin (TTX) indicating monosynaptic connectivity. We have previously found that orexin neurons are inhibited by local LH GABAergic neurons. Our hypothesis is that these local GABAergic interneurons are the target of the BF GABAergic arousal input. Conclusion BF GABAergic neurons drive arousal through projections to the LH. We propose that this arousal response is due to the inhibition of local GABAergic interneurons which in turn disinhibit the LH wake-promoting neurons including the orexin neurons. Support (if any) NS091126 and HL149630
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Uusisaari, M., and T. Knöpfel. "GABAergic synaptic communication in the GABAergic and non-GABAergic cells in the deep cerebellar nuclei." Neuroscience 156, no. 3 (October 2008): 537–49. http://dx.doi.org/10.1016/j.neuroscience.2008.07.060.
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Wenner, Peter. "Mechanisms of GABAergic Homeostatic Plasticity." Neural Plasticity 2011 (2011): 1–6. http://dx.doi.org/10.1155/2011/489470.
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Homeostatic plasticity ensures that appropriate levels of activity are maintained through compensatory adjustments in synaptic strength and cellular excitability. For instance, excitatory glutamatergic synapses are strengthened following activity blockade and weakened following increases in spiking activity. This form of plasticity has been described in a wide array of networks at several different stages of development, but most work and reviews have focussed on the excitatory inputs of excitatory neurons. Here we review homeostatic plasticity of GABAergic neurons and their synaptic connections. We propose a simplistic model for homeostatic plasticity of GABAergic components of the circuitry (GABAergic synapses onto excitatory neurons, excitatory connections onto GABAergic neurons, cellular excitability of GABAergic neurons): following chronic activity blockade there is a weakening of GABAergic inhibition, and following chronic increases in network activity there is a strengthening of GABAergic inhibition. Previous work on GABAergic homeostatic plasticity supports certain aspects of the model, but it is clear that the model cannot fully account for some results which do not appear to fit any simplistic rule. We consider potential reasons for these discrepancies.
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Frank, J. G., H. S. Jameson, C. Gorini, and D. Mendelowitz. "Mapping and Identification of GABAergic Neurons in Transgenic Mice Projecting to Cardiac Vagal Neurons in the Nucleus Ambiguus Using Photo-Uncaging." Journal of Neurophysiology 101, no. 4 (April 2009): 1755–60. http://dx.doi.org/10.1152/jn.91134.2008.
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The neural control of heart rate is determined primarily by the activity of preganglionic parasympathetic cardiac vagal neurons (CVNs) originating in the nucleus ambiguus (NA) in the brain stem. GABAergic inputs to CVNs play an essential role in determining the activity of these neurons including a robust inhibition during each inspiratory burst. The origin of GABAergic innervation has yet to be determined however. A transgenic mouse line expressing green florescent protein (GFP) in GABAergic cells was used in conjunction with caged glutamate to identify both clusters and individual GABAergic neurons that evoke inhibitory GABAergic synaptic responses in CVNs. Transverse slices were taken with CVNs patch-clamped in the whole cell configuration. Sections containing both the pre-Botzinger complex as well as the calamus scriptorius were divided into ∼90 quadrants, each 200 × 200 μm and were sequentially photostimulated. Inhibitory post synaptic currents (IPSCs) were recorded in CVNs after a 5-ms photostimulation of 50 μM caged glutamate. The four areas that contained GABAergic cells projecting to CVNs were 200 μm medial, 400 μm medial, 200 μm ventral, and 1,200 μm dorsal and 1,000 μm medial to patched CVNs. Once foci of GABAergic cells projecting to CVNs were determined, photostimulation of individual GABAergic neurons was conducted. The results from this study suggest that GABAergic cells located in four specific areas project to CVNs, and that these cells can be individually identified and stimulated using photouncaging to recruit GABAergic neurotransmission to CVNs.
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Shimizu-Okabe, Chigusa, Shiori Kobayashi, Jeongtae Kim, Yoshinori Kosaka, Masanobu Sunagawa, Akihito Okabe, and Chitoshi Takayama. "Developmental Formation of the GABAergic and Glycinergic Networks in the Mouse Spinal Cord." International Journal of Molecular Sciences 23, no. 2 (January 13, 2022): 834. http://dx.doi.org/10.3390/ijms23020834.
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Gamma-aminobutyric acid (GABA) and glycine act as inhibitory neurotransmitters. Three types of inhibitory neurons and terminals, GABAergic, GABA/glycine coreleasing, and glycinergic, are orchestrated in the spinal cord neural circuits and play critical roles in regulating pain, locomotive movement, and respiratory rhythms. In this study, we first describe GABAergic and glycinergic transmission and inhibitory networks, consisting of three types of terminals in the mature mouse spinal cord. Second, we describe the developmental formation of GABAergic and glycinergic networks, with a specific focus on the differentiation of neurons, formation of synapses, maturation of removal systems, and changes in their action. GABAergic and glycinergic neurons are derived from the same domains of the ventricular zone. Initially, GABAergic neurons are differentiated, and their axons form synapses. Some of these neurons remain GABAergic in lamina I and II. Many GABAergic neurons convert to a coreleasing state. The coreleasing neurons and terminals remain in the dorsal horn, whereas many ultimately become glycinergic in the ventral horn. During the development of terminals and the transformation from radial glia to astrocytes, GABA and glycine receptor subunit compositions markedly change, removal systems mature, and GABAergic and glycinergic action shifts from excitatory to inhibitory.
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Bracci, Enrico, and Stefano Panzeri. "Excitatory GABAergic Effects in Striatal Projection Neurons." Journal of Neurophysiology 95, no. 2 (February 2006): 1285–90. http://dx.doi.org/10.1152/jn.00598.2005.
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The ability of synaptically released GABA to facilitate action potential generation in striatal projection neurons was studied in brain slices using current-clamp, gramicidin-perforated whole cell recordings. Evoked GABAergic postsynaptic potentials (PSPs) were pharmacologically isolated with ionotropic glutamate receptor antagonists. Subthreshold depolarizing current injections were paired with GABAergic PSPs at different intervals. GABAergic PSPs were able to convert current injection-induced depolarizations from subthreshold to suprathreshold, but only when they preceded the current injection by an appropriate interval; accordingly, action potentials were observed 4–140 ms after the onset of the GABAergic PSP, and their likelihood was maximal after 50–60 ms. The GABAergic excitatory effects were fully blocked by the GABAA receptor antagonist bicuculline. Appropriately timed GABA PSPs decreased the time taken by current injections to depolarize projection neurons, causing an apparent reduction in the spike threshold. In control solution, the ability of evoked PSPs (comprising both glutamatergic and GABAergic components) to reach spike threshold was often impaired by bicuculline. We conclude that GABAergic PSPs can exert excitatory effects on projection neurons and that this ability crucially depends on the timing between the GABAergic event and a concomitant depolarizing input.
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Kolbaev, S. N., K. Achilles, H. J. Luhmann, and W. Kilb. "Effect of depolarizing GABAA-mediated membrane responses on excitability of Cajal-Retzius cells in the immature rat neocortex." Journal of Neurophysiology 106, no. 4 (October 2011): 2034–44. http://dx.doi.org/10.1152/jn.00699.2010.
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In immature neurons activation of ionotropic GABA receptors induces depolarizing membrane responses due to a high intracellular Cl− concentration ([Cl−]i). However, it is difficult to draw conclusions about the functional consequences of subthreshold GABAergic depolarizations, since GABAergic membrane shunting and additional effects on voltage-dependent ion channels or action potential threshold must be considered. To systematically investigate factors that determine the GABAergic effect on neuronal excitability we performed whole cell patch-clamp recordings from Cajal-Retzius cells in immature rat neocortex, using [Cl−]i between 10 and 50 mM. The effect of focal GABA application was quantified by measuring various parameters of GABAergic responses including the shift in minimal threshold current (rheobase). The rheobase shift was correlated with other parameters of the GABAergic responses by multiple linear regression analyses with a set of simple mathematical models. Our experiments demonstrate that focal GABA application induces heterogeneous rheobase shifts in Cajal-Retzius cells that could not be predicted reliably from [Cl−]i or the GABAergic membrane depolarization. Implementation of a linear mathematical model, which takes the GABAergic membrane conductance and the difference between action potential threshold and GABA reversal potential into account, resulted in a close correlation between calculated and experimentally obtained rheobase shifts. Addition of a linear term proportional to the GABAergic membrane depolarization improved the accuracy of correlation. The main advantage of using multiple linear regression with simple models is that direction and strength of GABAergic excitability shifts can be analyzed by using only measured parameters of GABAergic responses and with minimal a priori information about cellular parameters.
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Lombardi, Aniello, Peter Jedlicka, Heiko J. Luhmann, and Werner Kilb. "Coincident glutamatergic depolarizations enhance GABAA receptor-dependent Cl- influx in mature and suppress Cl- efflux in immature neurons." PLOS Computational Biology 17, no. 1 (January 19, 2021): e1008573. http://dx.doi.org/10.1371/journal.pcbi.1008573.
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The impact of GABAergic transmission on neuronal excitability depends on the Cl--gradient across membranes. However, the Cl--fluxes through GABAA receptors alter the intracellular Cl- concentration ([Cl-]i) and in turn attenuate GABAergic responses, a process termed ionic plasticity. Recently it has been shown that coincident glutamatergic inputs significantly affect ionic plasticity. Yet how the [Cl-]i changes depend on the properties of glutamatergic inputs and their spatiotemporal relation to GABAergic stimuli is unknown. To investigate this issue, we used compartmental biophysical models of Cl- dynamics simulating either a simple ball-and-stick topology or a reconstructed CA3 neuron. These computational experiments demonstrated that glutamatergic co-stimulation enhances GABA receptor-mediated Cl- influx at low and attenuates or reverses the Cl- efflux at high initial [Cl-]i. The size of glutamatergic influence on GABAergic Cl--fluxes depends on the conductance, decay kinetics, and localization of glutamatergic inputs. Surprisingly, the glutamatergic shift in GABAergic Cl--fluxes is invariant to latencies between GABAergic and glutamatergic inputs over a substantial interval. In agreement with experimental data, simulations in a reconstructed CA3 pyramidal neuron with physiological patterns of correlated activity revealed that coincident glutamatergic synaptic inputs contribute significantly to the activity-dependent [Cl-]i changes. Whereas the influence of spatial correlation between distributed glutamatergic and GABAergic inputs was negligible, their temporal correlation played a significant role. In summary, our results demonstrate that glutamatergic co-stimulation had a substantial impact on ionic plasticity of GABAergic responses, enhancing the attenuation of GABAergic inhibition in the mature nervous systems, but suppressing GABAergic [Cl-]i changes in the immature brain. Therefore, glutamatergic shift in GABAergic Cl--fluxes should be considered as a relevant factor of short-term plasticity.
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Erdö, Sándor L. "Peripheral GABAergic mechanisms." Trends in Pharmacological Sciences 6 (January 1985): 205–8. http://dx.doi.org/10.1016/0165-6147(85)90096-3.
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Chen, Z., A. Boxwell, C. Conte, T. Haas, A. Harley, D. H. Terman, S. P. Travers, and J. B. Travers. "Kv4 channel expression and kinetics in GABAergic and non-GABAergic rNST neurons." Journal of Neurophysiology 124, no. 6 (December 1, 2020): 1727–42. http://dx.doi.org/10.1152/jn.00396.2020.
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Here, we demonstrate that the transient outward K+ current IA occurs in both GABAergic and non-GABAergic neurons via Kv4.3 channels in the rostral (gustatory) solitary nucleus. Although found in both cell types, IA is more prevalent in non-GABAergic cells; a larger conductance at more negative potentials leads to a greater impact on spike initiation compared with GABAergic neurons. An IA window current further suggests that IA can regulate excitatory afferent input to the nucleus.
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Zhang, Jianhua, Mingchu Xi, Simon Fung, Charles Tobin, Sharon Sampogna, and Michael Chase. "027 GABAergic Neurons in the Dorsal Raphe Nucleus Are under the Influence of GABAergic Inputs from the Nucleus Pontis Oralis." Sleep 44, Supplement_2 (May 1, 2021): A12. http://dx.doi.org/10.1093/sleep/zsab072.026.
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Abstract Introduction Our previous study has shown that there is a direct connection between GABAergic neurons in the nucleus pontis oralis (NPO) and neurons of the dorsal raphe nucleus (DR), providing a morphological basis for the hypothesis that GABAergic inhibitory processes in NPO play an important role in the generation and maintenance of wakefulness as well as active (REM) sleep through the interaction with neurons in the DR. However, the target of such a GABAergic projection from the NPO within the DR is unknown. In the present study, a double-fluorescent labeling technique was employed to examine the target of GABAergic inputs to the DR. Methods Adult cats were deeply anesthetized and perfused transcardially. Subsequently, the brainstem containing the DR was removed, postfixed and cut into 15 μm coronal sections with a Reichert-Jung cryostat. The sections were immunostained with antibodies against GABA-A or GABA-B receptors and GABA following the procedure of double fluorescence immunohistochemistry. Results Under fluorescence microscopy, a large number of neurons were labeled with antibodies against either GABA-A receptor or GABA-B receptor. In addition, neurons labeled with antibody against GABA were observed in the DR. With double fluorescence immunohistochemical techniques, some neurons labeled by anti-GABA antibody were also stained with antibodies against GABA-A or GABA-B receptors. Conclusion The expression of GABA-A or GABA-B receptors by GABAergic neurons in the DR indicates that GABAergic neurons in the DR receive GABAergic inputs. Our previous study has demonstrated that these GABAergic inputs are from the NPO. These data provide a morphological foundation to support our hypothesis that, during wakefulness, NPO GABAergic “Executive” neurons suppress “Second-Order” GABAergic neurons in the DR, which, in turn, activate (disinhibit) serotonergic wake-on neurons in this nucleus. Support (if any) NS092383
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Fu, Huiqun, Fenghua Li, Sebastian Thomas, and Zhongjin Yang. "Hyperbaric oxygenation alleviates chronic constriction injury (CCI)-induced neuropathic pain and inhibits GABAergic neuron apoptosis in the spinal cord." Scandinavian Journal of Pain 17, no. 1 (October 1, 2017): 330–38. http://dx.doi.org/10.1016/j.sjpain.2017.08.014.
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AbstractBackground and aimsDysfunction of GABAergic inhibitory controls contributes to the development of neuropathic pain. We examined our hypotheses that (1) chronic constriction injury (CCI)-induced neuropathic pain is associated with increased spinal GABAergic neuron apoptosis, and (2) hyperbaric oxygen therapy (HBO) alleviates CCI-induced neuropathic pain by inhibiting GABAergic neuron apoptosis.MethodsMale rats were randomized into 3 groups: CCI, CCI+HBO and the control group (SHAM). Mechanical allodynia was tested daily following CCI procedure. HBO rats were treated at 2.4 atmospheres absolute (ATA) for 60 min once per day. The rats were euthanized and the spinal cord harvested on day 8 and 14 post-CCI. Detection of GABAergic cells and apoptosis was performed. The percentages of double positive stained cells (NeuN/GABA), cleaved caspase-3 or Cytochrome C in total GABAergic cells or in total NeuN positive cells were calculated.ResultsHBO significantly alleviated mechanical allodynia. CCI-induced neuropathic pain was associated with significantly increased spinal apoptotic GABA-positive neurons. HBO considerably decreased these spinal apoptotic cells. Cytochrome-C-positive neurons and cleaved caspase-3-positive neurons were also significantly higher in CCI rats. HBO significantly decreased these positive cells. Caspase-3 mRNA was also significantly higher in CCI rats. HBO reduced mRNA expression of caspase-3.ConclusionsCCI-induced neuropathic pain was associated with increased apoptotic GABAergic neurons induced by activation of key proteins of mitochondrial apoptotic pathways in the dorsal horn of the spinal cord. HBO alleviated CCI-induced neuropathic pain and reduced GABAergic neuron apoptosis. The beneficial effect of HBO may be via its inhibitory role in CCI-induced GABAergic neuron apoptosis by suppressing mitochondrial apoptotic pathways in the spinal cord.ImplicationsIncreased apoptotic GABAergic neurons induced by activation of key proteins of mitochondrial apoptotic pathways in the dorsal horn of the spinal cord is critical in CCI-induced neuropathic pain. The inhibitory role of HBO in GABAergic neuron apoptosis suppresses ongoing neuropathic pain.
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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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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.
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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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Shrestha, Shikshya, and Steven M. Offer. "Epigenetic Regulations of GABAergic Neurotransmission: Relevance for Neurological Disorders and Epigenetic Therapy." Medical Epigenetics 4, no. 1 (March 24, 2016): 1–19. http://dx.doi.org/10.1159/000444713.
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The GABAergic neurotransmission is a highly conserved system that has been attributed to various regulatory events. There has been a notable number of studies on the importance of GABAergic neurotransmission, both excitatory and inhibitory, in neurogenesis and central nervous system development including its control of neuronal cell proliferation and migration, synaptogenesis, dendrite formation and branching, and new neuronal cell integration in the adult brain. There has been remarkable progress in understanding the epigenetic regulations of GABAergic genes and their aberrant expressions in various neurological disorders such as autism spectrum disorder, Rett's syndrome, schizophrenia and PWS. The roles of histone modifications, chromatin looping and gene methylation have been implicated in altered regulations of key genes in the GABAergic pathway. Taken together, they affect the functioning of GABAergic neurotransmission and disrupt various events in brain development. Here, we focus on the role of GABAergic neurotransmission in brain development and on how various genetic and epigenetic events regulate the GABAergic genes in pre- and postnatal brain. We also discuss how these regulatory mechanisms contribute to the pathogenesis of neurological disorders and, therefore, can be used in the development of potential epigenetic therapy for these diseases.
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Zheng, Zhongfan, Xiumei Zhang, Junqiang Liu, Ping He, Shan Zhang, Yongning Zhang, Jie Gao, et al. "GABAergic synapses suppress intestinal innate immunity via insulin signaling in Caenorhabditis elegans." Proceedings of the National Academy of Sciences 118, no. 20 (May 10, 2021): e2021063118. http://dx.doi.org/10.1073/pnas.2021063118.
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GABAergic neurotransmission constitutes a major inhibitory signaling mechanism that plays crucial roles in central nervous system physiology and immune cell immunomodulation. However, its roles in innate immunity remain unclear. Here, we report that deficiency in the GABAergic neuromuscular junctions (NMJs) of Caenorhabditis elegans results in enhanced resistance to pathogens, whereas pathogen infection enhances the strength of GABAergic transmission. GABAergic synapses control innate immunity in a manner dependent on the FOXO/DAF-16 but not the p38/PMK-1 pathway. Our data reveal that the insulin-like peptide INS-31 level was dramatically decreased in the GABAergic NMJ GABAAR-deficient unc-49 mutant compared with wild-type animals. C. elegans with ins-31 knockdown or loss of function exhibited enhanced resistance to Pseudomonas aeruginosa PA14 exposure. INS-31 may act downstream of GABAergic NMJs and in body wall muscle to control intestinal innate immunity in a cell-nonautonomous manner. Our results reveal a signaling axis of synapse–muscular insulin–intestinal innate immunity in vivo.
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Kilb, Werner. "Development of the GABAergic System from Birth to Adolescence." Neuroscientist 18, no. 6 (September 27, 2011): 613–30. http://dx.doi.org/10.1177/1073858411422114.
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The neurotransmitter GABA (γ-aminobutyric acid), acting via inotropic GABAA and metabotropic GABAB receptors, plays an essential role in a variety of distinct neuronal processes, including regulation of neuronal excitability, determination of temporal aspects of spike trains, control of the size and propagation of neuronal assemblies, generation of oscillatory activity, and neuronal plasticity. Although the developmental switch between excitatory and inhibitory GABAA receptor–mediated responses is widely appreciated, the fact that the postnatal maturation of the GABAergic system lasts until late adolescence is not so persuasively promoted. This review summarizes recent knowledge of the maturation of various aspects of the GABAergic systems, like functional expression of GABA synthesizing/degrading enzymes and transporters, density of GABAergic synapses, GABAergic projection patterns, GABA receptor subunit composition, and properties of GABAergic interneurons, with an emphasis on the late developmental alterations. In addition, some aspects of the development of mental capabilities during adolescence and their relation the delayed maturation of the GABAergic system are presented.
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Morita, Kenji, Kunichika Tsumoto, and Kazuyuki Aihara. "Possible Effects of Depolarizing GABAA Conductance on the Neuronal Input–Output Relationship: A Modeling Study." Journal of Neurophysiology 93, no. 6 (June 2005): 3504–23. http://dx.doi.org/10.1152/jn.00988.2004.
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Recent in vitro experiments revealed that the GABAA reversal potential is about 10 mV higher than the resting potential in mature mammalian neocortical pyramidal cells; thus GABAergic inputs could have facilitatory, rather than inhibitory, effects on action potential generation under certain conditions. However, how the relationship between excitatory input conductances and the output firing rate is modulated by such depolarizing GABAergic inputs under in vivo circumstances has not yet been understood. We examine herewith the input–output relationship in a simple conductance-based model of cortical neurons with the depolarized GABAA reversal potential, and show that a tonic depolarizing GABAergic conductance up to a certain amount does not change the relationship between a tonic glutamatergic driving conductance and the output firing rate, whereas a higher GABAergic conductance prevents spike generation. When the tonic glutamatergic and GABAergic conductances are replaced by in vivo–like highly fluctuating inputs, on the other hand, the effect of depolarizing GABAergic inputs on the input–output relationship critically depends on the degree of coincidence between glutamatergic input events and GABAergic ones. Although a wide range of depolarizing GABAergic inputs hardly changes the firing rate of a neuron driven by noncoincident glutamatergic inputs, a certain range of these inputs considerably decreases the firing rate if a large number of driving glutamatergic inputs are coincident with them. These results raise the possibility that the depolarized GABAA reversal potential is not a paradoxical mystery, but is instead a sophisticated device for discriminative firing rate modulation.
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Kawaguchi, Yasuo. "Selective Cholinergic Modulation of Cortical GABAergic Cell Subtypes." Journal of Neurophysiology 78, no. 3 (September 1, 1997): 1743–47. http://dx.doi.org/10.1152/jn.1997.78.3.1743.
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Kawaguchi, Yasuo. Selective cholinergic modulation of cortical GABAergic cell subtypes. J. Neurophysiol. 78: 1743–1747, 1997. Acetylcholine from the basal forebrain and γ-aminobutyric acid (GABA) from intracortical inhibitory interneurons exert strong influence on the cortical activity and may interact with each other. Cholinergic or muscarinic agonists indeed induced GABAergic postsynaptic currents in pyramidal cells by exciting inhibitory interneurons that have recently been classified into several distinct subtypes on the basis of the physiological, chemical, and morphological criteria. Cholinergic effects on GABAergic cell subtypes were investigated of rat frontal cortex by in vitro whole cell recording with intracellular staining in frontal cortex of young rats. GABAergic cell subtypes were identified physiologically by firing responses to depolarizing current pulses and immunohistochemically as containing parvalbumin, somatostatin, vasoactive intestinal polypeptide (VIP), or cholecystokinin (CCK). Carbachol (10 μM) or (+)-muscarine (3 μM) affected the activities of peptide-containing GABAergic cells with regular- or burst-spiking characteristics, but not of GABAergic cells with fast-spiking characteristics containing the calcium-binding protein parvalbumin orGABAergic cells with late-spiking characteristics. Somatostatin- or VIP-immunoreactive cells were depolarized with spike firing. CCK-immunoreactive cells were affected heterogeneously by cholinergic agonists. Larger CCK cells were hyperpolarized, followed by a slow depolarization, whereas smaller CCK cells were only depolarized. These results suggest that the excitability of cortical GABAergic cell subtypes is differentially regulated by acetylcholine. Differences in cholinergic responses suggest a distinct functional role of each GABAergic cell subtype.
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Rubi, Lena, and Jean-Marc Fritschy. "Increased GABAergic transmission in neuropeptide Y-expressing neurons in the dopamine-depleted murine striatum." Journal of Neurophysiology 123, no. 4 (April 1, 2020): 1496–503. http://dx.doi.org/10.1152/jn.00059.2020.
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As the main input nucleus of the basal ganglia, the striatum plays a central role in planning, control, and execution of movement and motor skill learning. More than 90% of striatal neurons, so-called medium spiny neurons (MSN), are GABAergic projection neurons, innervating primarily the substantia nigra pars reticulata or the globus pallidus internus. The remaining neurons are GABAergic and cholinergic interneurons, synchronizing and controlling striatal output by reciprocal connections with MSN. Besides prominent local cholinergic influence, striatal function is globally regulated by dopamine (DA) from the nigrostriatal pathway. Little is known about whether DA depletion, as occurs in Parkinson’s disease, affects the activity of striatal interneurons. Here we focused on neuropeptide Y (NPY)-expressing interneurons, which are among the major subgroups of GABAergic interneurons in the striatum. We investigated the effects of striatal DA depletion on GABAergic transmission in NPY interneurons by electrophysiologically recording GABAergic spontaneous (s) and miniature (m) inhibitory postsynaptic currents (IPSCs) in identified NPY interneurons in slices from 6-hydroxydopamine (6-OHDA)- and vehicle-injected transgenic NPY-humanized Renilla green fluorescent protein (hrGFP) mice with the whole cell patch-clamp technique. We report a significant increase in sIPSC and mIPSC frequency as well as the occurrence of giant synaptic and burst sIPSCs in the 6-OHDA group, suggesting changes in GABAergic circuit activity and synaptic transmission. IPSC kinetics remained unchanged, pointing to mainly presynaptic changes in GABAergic transmission. These results show that chronic DA depletion following 6-OHDA injection causes activity-dependent and -independent increase of synaptic GABAergic inhibition onto striatal NPY interneurons, confirming their involvement in the functional impairments of the DA-depleted striatum. NEW & NOTEWORTHY Neuropeptide Y (NPY) interneurons regulate the function of striatal projection neurons and are upregulated upon dopamine depletion in the striatum. Here we investigated how dopamine depletion affects NPY circuits and show electrophysiologically that it leads to the occurrence of giant synaptic and burst GABAergic spontaneous inhibitory postsynaptic currents (IPSCs) and to an activity-independent increase in GABAergic miniature IPSC frequency in NPY neurons. We suggest that degeneration of dopaminergic terminals in the striatum causes functional changes in striatal GABAergic function.
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Wang, Di, Qingchen Guo, Yu Zhou, Zheng Xu, Su-Wan Hu, Xiang-Xi Kong, Yu-Mei Yu, et al. "GABAergic Neurons in the Dorsal–Intermediate Lateral Septum Regulate Sleep–Wakefulness and Anesthesia in Mice." Anesthesiology 135, no. 3 (July 13, 2021): 463–81. http://dx.doi.org/10.1097/aln.0000000000003868.
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Background The γ-aminobutyric acid–mediated (GABAergic) inhibitory system in the brain is critical for regulation of sleep–wake and general anesthesia. The lateral septum contains mainly GABAergic neurons, being cytoarchitectonically divided into the dorsal, intermediate, and ventral parts. This study hypothesized that GABAergic neurons of the lateral septum participate in the control of wakefulness and promote recovery from anesthesia. Methods By employing fiber photometry, chemogenetic and optogenetic neuronal manipulations, anterograde tracing, in vivo electrophysiology, and electroencephalogram/electromyography recordings in adult male mice, the authors measured the role of lateral septum GABAergic neurons to the control of sleep–wake transition and anesthesia emergence and the corresponding neuron circuits in arousal and emergence control. Results The GABAergic neurons of the lateral septum exhibited high activities during the awake state by in vivo fiber photometry recordings (awake vs. non–rapid eye movement sleep: 3.3 ± 1.4% vs. –1.3 ± 1.2%, P < 0.001, n = 7 mice/group; awake vs. anesthesia: 2.6 ± 1.2% vs. –1.3 ± 0.8%, P < 0.001, n = 7 mice/group). Using chemogenetic stimulation of lateral septum GABAergic neurons resulted in a 100.5% increase in wakefulness and a 51.2% reduction in non–rapid eye movement sleep. Optogenetic activation of these GABAergic neurons promoted wakefulness from sleep (median [25th, 75th percentiles]: 153.0 [115.9, 179.7] s to 4.0 [3.4, 4.6] s, P = 0.009, n = 5 mice/group) and accelerated emergence from isoflurane anesthesia (514.4 ± 122.2 s vs. 226.5 ± 53.3 s, P < 0.001, n = 8 mice/group). Furthermore, the authors demonstrated that the lateral septum GABAergic neurons send 70.7% (228 of 323 cells) of monosynaptic projections to the ventral tegmental area GABAergic neurons, preferentially inhibiting their activities and thus regulating wakefulness and isoflurane anesthesia depth. Conclusions The results uncover a fundamental role of the lateral septum GABAergic neurons and their circuit in maintaining awake state and promoting general anesthesia emergence time. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New
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Chattopadhyaya, Bidisha. "Molecular Mechanisms Underlying Activity-Dependent GABAergic Synapse Development and Plasticity and Its Implications for Neurodevelopmental Disorders." Neural Plasticity 2011 (2011): 1–8. http://dx.doi.org/10.1155/2011/734231.
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GABAergic interneurons are critical for the normal function and development of neural circuits, and their dysfunction is implicated in a large number of neurodevelopmental disorders. Experience and activity-dependent mechanisms play an important role in GABAergic circuit development, also recent studies involve a number of molecular players involved in the process. Emphasizing the molecular mechanisms of GABAergic synapse formation, in particular basket cell perisomatic synapses, this paper draws attention to the links between critical period plasticity, GABAergic synapse maturation, and the consequences of its dysfunction on the development of the nervous system.
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Gourévitch, Boris, Elena J. Mahrt, Warren Bakay, Cameron Elde, and Christine V. Portfors. "GABAA receptors contribute more to rate than temporal coding in the IC of awake mice." Journal of Neurophysiology 123, no. 1 (January 1, 2020): 134–48. http://dx.doi.org/10.1152/jn.00377.2019.
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Speech is our most important form of communication, yet we have a poor understanding of how communication sounds are processed by the brain. Mice make great model organisms to study neural processing of communication sounds because of their rich repertoire of social vocalizations and because they have brain structures analogous to humans, such as the auditory midbrain nucleus inferior colliculus (IC). Although the combined roles of GABAergic and glycinergic inhibition on vocalization selectivity in the IC have been studied to a limited degree, the discrete contributions of GABAergic inhibition have only rarely been examined. In this study, we examined how GABAergic inhibition contributes to shaping responses to pure tones as well as selectivity to complex sounds in the IC of awake mice. In our set of long-latency neurons, we found that GABAergic inhibition extends the evoked firing rate range of IC neurons by lowering the baseline firing rate but maintaining the highest probability of firing rate. GABAergic inhibition also prevented IC neurons from bursting in a spontaneous state. Finally, we found that although GABAergic inhibition shaped the spectrotemporal response to vocalizations in a nonlinear fashion, it did not affect the neural code needed to discriminate vocalizations, based either on spiking patterns or on firing rate. Overall, our results emphasize that even if GABAergic inhibition generally decreases the firing rate, it does so while maintaining or extending the abilities of neurons in the IC to code the wide variety of sounds that mammals are exposed to in their daily lives. NEW & NOTEWORTHY GABAergic inhibition adds nonlinearity to neuronal response curves. This increases the neuronal range of evoked firing rate by reducing baseline firing. GABAergic inhibition prevents bursting responses from neurons in a spontaneous state, reducing noise in the temporal coding of the neuron. This could result in improved signal transmission to the cortex.
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Kwon, Taekyung, Angel Merchán-Pérez, Emiliano M. Rial Verde, José-Rodrigo Rodríguez, Javier DeFelipe, and Rafael Yuste. "Ultrastructural, Molecular and Functional Mapping of GABAergic Synapses on Dendritic Spines and Shafts of Neocortical Pyramidal Neurons." Cerebral Cortex 29, no. 7 (August 3, 2018): 2771–81. http://dx.doi.org/10.1093/cercor/bhy143.
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Abstract The location of GABAergic synapses on dendrites is likely key for neuronal integration. In particular, inhibitory inputs on dendritic spines could serve to selectively veto or modulate individual excitatory inputs, greatly expanding the computational power of individual neurons. To investigate this, we have undertaken a combined functional, molecular, and ultrastructural mapping of the location of GABAergic inputs onto dendrites of pyramidal neurons from upper layers of juvenile mouse somatosensory cortex. Using two-photon uncaging of GABA, intracellular labeling with gerphyrin intrabodies, and focused ion beam milling with scanning electron microscopy, we find that most (96–98%) spines lack GABAergic synapses, although they still display GABAergic responses, potentially due to extrasynaptic GABA receptors. We conclude that GABAergic inputs, in practice, contact dendritic shafts and likely control clusters of excitatory inputs, defining functional zones on dendrites.
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Hernández-Vázquez, Fabiola, Julieta Garduño, and Salvador Hernández-López. "GABAergic modulation of serotonergic neurons in the dorsal raphe nucleus." Reviews in the Neurosciences 30, no. 3 (April 24, 2019): 289–303. http://dx.doi.org/10.1515/revneuro-2018-0014.
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Abstract The dorsal raphe nucleus (DRN), located in the brainstem, is involved in several functions such as sleep, temperature regulation, stress responses, and anxiety behaviors. This nucleus contains the largest population of serotonin expressing neurons in the brain. Serotonergic DRN neurons receive tonic γ-aminobutyric acid (GABA)inhibitory inputs from several brain areas, as well as from interneurons within the same nucleus. Serotonergic and GABAergic neurons in the DRN can be distinguished by their size, location, pharmacological responses, and electrophysiological properties. GABAergic neurons regulate the excitability of DRN serotonergic neurons and the serotonin release in different brain areas. Also, it has been shown that GABAergic neurons can synchronize the activity of serotonergic neurons across functions such as sleep or alertness. Moreover, dysregulation of GABA signaling in the DRN has been linked to psychiatric disorders such as anxiety and depression. This review focuses on GABAergic transmission in the DRN. The interaction between GABAergic and serotonergic neurons is discussed considering some physiological implications. Also, the main electrophysiological and morphological characteristics of serotonergic and GABAergic neurons are described.
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Liu, Peng, Xiao Zhang, Xiaolan He, Zhenhua Jiang, Qun Wang, and Yan Lu. "Spinal GABAergic neurons are under feed-forward inhibitory control driven by Aδ and C fibers in Gad2 td-Tomato mice." Molecular Pain 17 (January 2021): 174480692199262. http://dx.doi.org/10.1177/1744806921992620.
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Background Spinal GABAergic neurons act as a critical modulator in sensory transmission like pain or itch. The monosynaptic or polysynaptic primary afferent inputs onto GABAergic neurons, along with other interneurons or projection neurons make up the direct and feed-forward inhibitory neural circuits. Previous research indicates that spinal GABAergic neurons mainly receive excitatory inputs from Aδ and C fibers. However, whether they are controlled by other inhibitory sending signals is not well understood. Methods We applied a transgenic mouse line in which neurons co-expressed the GABA-synthesizing enzyme Gad65 and the enhanced red fluorescence (td-Tomato) to characterize the features of morphology and electrophysiology of GABAergic neurons. Patch-clamp whole cell recordings were used to record the evoked postsynaptic potentials of fluorescent neurons in spinal slices in response to dorsal root stimulation. Results We demonstrated that GABAergic neurons not only received excitatory drive from peripheral Aβ, Aδ and C fibers, but also received inhibitory inputs driven by Aδ and C fibers. The evoked inhibitory postsynaptic potentials (eIPSPs) mediated by C fibers were mainly Glycinergic (66.7%) as well as GABAergic mixed with Glycinergic (33.3%), whereas the inhibition mediated by Aδ fibers was predominately both GABA and Glycine-dominant (57.1%), and the rest of which was purely Glycine-dominant (42.9%). Conclusion These results indicated that spinal GABAergic inhibitory neurons are under feedforward inhibitory control driven by primary C and Aδ fibers, suggesting that this feed-forward inhibitory pathway may play an important role in balancing the excitability of GABAergic neurons in spinal dorsal horn.
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Mills, Demetra J. "The Aging GABAergic System and Its Nutritional Support." Journal of Nutrition and Metabolism 2021 (April 25, 2021): 1–17. http://dx.doi.org/10.1155/2021/6655064.
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Aging is associated with a decline in hormones and an associated decline in GABAergic function and calcium and ion current dysregulation. Neurosteroid hormones act as direct calcium channel blockers, or they can act indirectly on calcium channels through their interaction with GABA receptors. The calcium channel dysfunction associated with hormone loss further leads to an excitatory cell state, which can ultimately lead to cell death. The calcium theory of aging posits that cellular mechanisms, which maintain the homeostasis of cytosol Ca2+ concentration, play a key role in brain aging and that sustained changes in Ca2+ homeostasis provide the final common pathway for age-associated brain changes. There is a link between hormone loss and calcium dysregulation. Loss of calcium regulation associated with aging can lead to an excitatory cell state, primarily in the mitochondria and nerve cells, which can ultimately lead to cell death if not kept in check. A decline in GABAergic function can also be specifically tied to declines in progesterone, allopregnanolone, and DHEA levels associated with aging. This decline in GABAergic function associated with hormone loss ultimately affects GABAergic inhibition or excitement and calcium regulation throughout the body. In addition, declines in GABAergic function can also be tied to vitamin status and to toxic chemicals in the food supply. The decline in GABAergic function associated with aging has an effect on just about every body organ system. Nutritional support of the GABAergic system with supportive foods, vitamins, and GABA or similar GABA receptor ligands may address some of the GABAergic dysfunction associated with aging.
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Lasztóczi, Bálint, Gabriella Nyitrai, László Héja, and Julianna Kardos. "Synchronization of GABAergic Inputs to CA3 Pyramidal Cells Precedes Seizure-Like Event Onset in Juvenile Rat Hippocampal Slices." Journal of Neurophysiology 102, no. 4 (October 2009): 2538–53. http://dx.doi.org/10.1152/jn.91318.2008.
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Here we address how dynamics of glutamatergic and GABAergic synaptic input to CA3 pyramidal cells contribute to spontaneous emergence and evolution of recurrent seizure-like events (SLEs) in juvenile (P10-13) rat hippocampal slices bathed in low-[Mg2+] artificial cerebrospinal fluid. In field potential recordings from the CA3 pyramidal layer, a short epoch of high-frequency oscillation (HFO; 400–800 Hz) was observed during the first 10 ms of SLE onset. GABAergic synaptic input currents to CA3 pyramidal cells were synchronized and coincided with HFO, whereas the glutamatergic input lagged by ∼10 ms. If the intracellular [Cl−] remained unperturbed (cell-attached recordings) or was set high with whole cell electrode solution, CA3 pyramidal cell firing peaked with HFO and GABAergic input. By contrast, with low intracellular [Cl−], spikes of CA3 pyramidal cells lagged behind HFO and GABAergic input. This temporal arrangement of HFO, synaptic input sequence, synchrony of GABAergic currents, and pyramidal cell firing emerged gradually with preictal discharges until the SLE onset. Blockade of GABAA receptor-mediated currents by picrotoxin reduced the inter-SLE interval and the number of preictal discharges and did not block recurrent SLEs. Our data suggest that dynamic changes of the functional properties of GABAergic input contribute to ictogenesis and GABAergic and glutamatergic inputs are both excitatory at the instant of SLE onset. At the SLE onset GABAergic input contributes to synchronization and recruitment of pyramidal cells. We conjecture that this network state is reached by an activity-dependent shift in GABA reversal potential during the preictal phase.
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Nakamura, Michiko, Il-Sung Jang, Hitoshi Ishibashi, Shigenori Watanabe, and Norio Akaike. "Possible Roles of Kainate Receptors on GABAergic Nerve Terminals Projecting to Rat Substantia Nigra Dopaminergic Neurons." Journal of Neurophysiology 90, no. 3 (September 2003): 1662–70. http://dx.doi.org/10.1152/jn.01165.2002.
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GABAergic afferent inputs are thought to play an important role in the control of the firing pattern of substantia nigra pars compacta (SNc) dopaminergic neurons. We report here the actions of presynaptic kainite (KA) receptors in GABAergic transmission of rat SNc dopaminergic neurons. In mechanically dissociated rat SNc dopaminergic neurons attached with native presynaptic nerve terminals, GABAergic miniature inhibitory postsynaptic currents (mIPSCs) were recorded by use of conventional whole cell patch recording mode. In the voltage-clamp condition, KA (3 μM) significantly increased GABAergic mIPSC frequency without affecting the current amplitude. This facilitatory effect of KA was not affected in the presence of 20 μM GYKI52466, a selective AMPA receptor antagonist, but was completely inhibited in the presence of 20 μM CNQX, an AMPA/KA receptor antagonist. Presynaptic KA receptors on GABAergic terminals were mainly permeable to Na+ but impermeable to Ca2+ because KA-induced facilitation of mIPSC frequency was completely suppressed in either Na+-free or Ca2+-free external solutions, and in the presence of 200 μM Cd2+, a general voltage-dependent Ca2+ channel blocker. In the slice preparation, KA increased GABAergic spontaneous mIPSC frequency, but significantly suppressed evoked IPSC (eIPSC) amplitude. However, this inhibitory action on eIPSCs was reversed by 10 μM CGP55845 , a selective GABAB receptor antagonist, implicating the possible involvement of GABAB autoreceptors in KA-induced modulation of GABAergic transmission. Thus presynaptic KA receptors on GABAergic nerve terminals synapsing onto SNc neurons may play functional roles contributing the fine control of neuronal excitability and firing pattern of SNc.
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Endo, Toshiaki, Yuchio Yanagawa, Kunihiko Obata, and Tadashi Isa. "Nicotinic Acetylcholine Receptor Subtypes Involved in Facilitation of GABAergic Inhibition in Mouse Superficial Superior Colliculus." Journal of Neurophysiology 94, no. 6 (December 2005): 3893–902. http://dx.doi.org/10.1152/jn.00211.2005.
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The superficial superior colliculus (sSC) is a key station in the sensory processing related to visual salience. The sSC receives cholinergic projections from the parabigeminal nucleus, and previous studies have revealed the presence of several different nicotinic acetylcholine receptor (nAChR) subunits in the sSC. In this study, to clarify the role of the cholinergic inputs to the sSC, we examined current responses induced by ACh in GABAergic and non-GABAergic sSC neurons using in vitro slice preparations obtained from glutamate decarboxylase 67-green fluorescent protein (GFP) knock-in mice in which GFP is specifically expressed in GABAergic neurons. Brief air pressure application of acetylcholine (ACh) elicited nicotinic inward current responses in both GABAergic and non-GABAergic neurons. The inward current responses in the GABAergic neurons were highly sensitive to a selective antagonist for α3β2- and α6β2-containing receptors, α-conotoxin MII (αCtxMII). A subset of these neurons exhibited a faster α-bungarotoxin-sensitive inward current component, indicating the expression of α7-containing nAChRs. We also found that the activation of presynaptic nAChRs induced release of GABA, which elicited a burst of miniature inhibitory postsynaptic currents mediated by GABAA receptors in non-GABAergic neurons. This ACh-induced GABA release was mediated mainly by αCtxMII-sensitive nAChRs and resulted from the activation of voltage-dependent calcium channels. Morphological analysis revealed that recorded GFP-positive neurons are interneurons and GFP-negative neurons include projection neurons. These findings suggest that nAChRs are involved in the regulation of GABAergic inhibition and modulate visual processing in the sSC.
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Li, Juan, Luting Chen, Feng Guo, Xiaohua Han, and Florinda Ferreri. "The Effects of GABAergic System under Cerebral Ischemia: Spotlight on Cognitive Function." Neural Plasticity 2020 (September 28, 2020): 1–9. http://dx.doi.org/10.1155/2020/8856722.
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In this review, we present evidence about the changes of the GABAergic system on the hippocampus under the ischemic environment, which may be an underlying mechanism to the ischemia-induced cognitive deficit. GABAergic system, in contrast to the glutamatergic system, is considered to play an inhibitory effect on the central nervous system over the past several decades. It has received widespread attention in the area of schizophrenia and epilepsy. The GABAergic system has a significant effect in promoting neural development and formation of local neural circuits of the brain, which is the structural basis of cognitive function. There have been a number of reviews describing changes in the GABAergic system in cerebral ischemia in recent years. However, no study has investigated the changes in the system in the hippocampus during cerebral ischemic injury, which results in cognitive impairment, particularly at the chronic ischemic stage and the late phase of ischemia. We present a review of the changes of the GABAergic system in the hippocampus under ischemia, including GABA interneurons, extracellular GABA neurotransmitter, and GABA receptors. Several studies are also listed correlating amelioration of cognitive impairment by regulating the GABAergic system in the hippocampus damaged under ischemia. Furthermore, exogenous cell transplantation, which improves cognition by modulating the GABAergic system, will also be described in this review to bring new insight and strategy on solving cognitive deficits caused by cerebral ischemia.
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Naumov, Victor, Julia Heyd, Fauve de Arnal, and Ursula Koch. "Analysis of excitatory and inhibitory neuron types in the inferior colliculus based on Ih properties." Journal of Neurophysiology 121, no. 6 (June 1, 2019): 2126–39. http://dx.doi.org/10.1152/jn.00594.2018.
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The inferior colliculus (IC) is a large midbrain nucleus that integrates inputs from many auditory brainstem and cortical structures. Despite its prominent role in auditory processing, the various cell types and their connections within the IC are not well characterized. To further separate GABAergic and non-GABAergic neuron types according to their physiological properties, we used a mouse model that expresses channelrhodopsin and enhanced yellow fluorescent protein in all GABAergic neurons and allows identification of GABAergic cells by light stimulation. Neuron types were classified upon electrophysiological measurements of the hyperpolarizing-activated current ( Ih) in acute brain slices of young adult mice. All GABAergic neurons from our sample displayed slow-activating Ih with moderate amplitudes, whereas a subset of excitatory neurons showed fast-activating Ih with large amplitudes. This is in agreement with our finding that immunoreactivity against the fast-gating hyperpolarization-activated and cyclic-nucleotide-gated 1 (HCN1) channel was present around excitatory neurons, whereas the slow-gating HCN4 channel was found perisomatically around most inhibitory neurons. Ih properties and neurotransmitter types were correlated with firing patterns to depolarizing current pulses. All GABAergic neurons displayed adapting firing patterns very similar to the majority of glutamatergic neurons. About 15% of the glutamatergic neurons showed an onset spiking pattern, always in combination with large and fast Ih. We conclude that HCN channel subtypes are differentially distributed in IC neuron types and correlate with neurotransmitter type and firing pattern. In contrast to many other brain regions, membrane properties and firing patterns were similar in GABAergic neurons and about one-third of the excitatory neurons. NEW & NOTEWORTHY Neuron types in the central nucleus of the auditory midbrain are not well characterized regarding their transmitter type, ion channel composition, and firing pattern. The present study shows that GABAergic neurons have slowly activating hyperpolarizing-activated current ( Ih) and an adaptive firing pattern whereas at least four types of glutamatergic neurons exist regarding their Ih properties and firing patterns. Many of the glutamatergic neurons were almost indistinguishable from the GABAergic neurons regarding Ih properties and firing pattern.
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Wang, Xin, Zheng-Gui Huang, Allison Gold, Evguenia Bouairi, Cory Evans, Michael C. Andresen, and David Mendelowitz. "Propofol Modulates γ-Aminobutyric Acid–mediated Inhibitory Neurotransmission to Cardiac Vagal Neurons in the Nucleus Ambiguus." Anesthesiology 100, no. 5 (May 1, 2004): 1198–205. http://dx.doi.org/10.1097/00000542-200405000-00023.
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Background Although it is well recognized that anesthetics modulate the central control of cardiorespiratory homeostasis, the cellular mechanisms by which anesthetics alter cardiac parasympathetic activity are poorly understood. One common site of action of anesthetics is inhibitory neurotransmission. This study investigates the effect of propofol on gamma-aminobutyric acid-mediated (GABAergic) and glycinergic neurotransmission to cardiac parasympathetic neurons. Methods Cardiac parasympathetic neurons were identified in vitro by the presence of a retrograde fluorescent tracer, and spontaneous GABAergic and glycinergic synaptic currents were examined using whole cell patch clamp techniques. Results Propofol at concentrations of 1.0 microm and greater significantly (P < 0.05) increased the duration and decay time of spontaneous GABAergic inhibitory postsynaptic currents. To determine whether the action of propofol was at presynaptic or postsynaptic sites, tetrodotoxin was applied to isolate miniature inhibitory postsynaptic currents. Propofol at concentrations of 1.0 microm and greater significantly (P < 0.05) prolonged the decay time and duration of miniature inhibitory postsynaptic currents, indicating that propofol directly alters GABAergic neurotransmission at a postsynaptic site. Propofol at high concentrations (> or =50 microm) also inhibited the frequency of both GABAergic inhibitory postsynaptic currents and miniature inhibitory postsynaptic currents. Propofol at concentrations up to 50 microm had no effect on glycinergic neurotransmission. Conclusions Propofol may vary heart rate by modulating GABAergic neurotransmission to cardiac parasympathetic neurons. At clinically relevant concentrations (> or =1.0 microm), propofol facilitated GABAergic responses in cardiac vagal neurons by increasing decay time, which would increase inhibition of cardioinhibitory cardiac vagal neurons and evoke an increase in heart rate. At higher supraclinical concentrations (> or =50 microm), propofol inhibits GABAergic neurotransmission to cardiac vagal neurons, which would evoke a decrease in heart rate.
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Zhang, J., S. Sampogna, M. Xi, S. J. Fung, C. Tobin, and M. H. Chase. "0067 An Anatomic Substrate for GABAergic Processes to Suppress Active Sleep and Promote Wakefulness in the Nucleus Pontis Oralis." Sleep 43, Supplement_1 (April 2020): A27. http://dx.doi.org/10.1093/sleep/zsaa056.065.
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Abstract Introduction Our previous electrophysiologic data have provided compelling evidence that GABAergic processes in the nucleus pontis oralis (NPO) play a critical role in the generation and maintenance of wakefulness as well as active (REM) sleep (AS). We therefore hypothesized that one of the neuronal mechanisms of GABA actions in the NPO to promote wakefulness and suppress AS is due to a direct GABAergic inhibition of NPO neurons that generate AS (AS-generator neurons). However, the anatomical substrate for this inhibition is undetermined. Accordingly, the present study was undertaken to examine whether there is any direct interaction between GABAergic neurons and glutamatergic AS-generator neurons in the NPO. Methods Adult cats were deeply anesthetized and perfused transcardially. The brainstem containing the NPO was removed, postfixed and cut into 15 μm coronal sections with a Reichert-Jung cryostat. The sections were incubated with a mixture of a rabbit polyclonal antibodies against glutamine and GABA following the procedure of double fluorescence immunohistochemistry. Results There was a large number of neuronal somata labeled by anti-glutamine antibody and terminals labeled by anti-GABA antibody in the NPO. These glutamine-positive neurons were medium to large, multipolar cells (> 20 μm), which resemble glutamatergic, AS-generator neurons that have been previously identified in the NPO. Specifically, majority of glutamatergic neuronal somata were closely apposed by multiple GABAergic terminals, indicating that AS-generator neurons in the NPO receive direct GABAergic inputs. Conclusion The present results demonstrate that a direct connection exists between glutamatergic AS-generator neurons and GABAergic processes in the NPO. These data provide the anatomical evidence which supports our hypothesis that the pontine GABAergic control of wakefulness and active sleep is partially mediated via GABAergic processes project to NPO AS-generator neurons that suppress the activity of these cells. Support NS092383
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Sans-Dublanc, Arnau, Adrià Razzauti, Srinidhi Desikan, Marta Pascual, Hannah Monyer, and Carlos Sindreu. "Septal GABAergic inputs to CA1 govern contextual memory retrieval." Science Advances 6, no. 44 (October 2020): eaba5003. http://dx.doi.org/10.1126/sciadv.aba5003.
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The CA1 output region of the hippocampus plays an essential role in the retrieval of episodic memories. γ-Aminobutyric acid–releasing (GABAergic) long-range projections from the medial septum (MS) densely innervate the hippocampus, but whether septal inputs regulate memory expression remains elusive. We found that the MS to CA1 connection is recruited during recall of a contextual fear memory. Chemogenetic silencing of CA1-projecting MS neurons or septal GABAergic terminals within CA1 blocked memory retrieval. Photostimulation of septal GABAergic terminals in CA1 selectively inhibited interneurons. Abrogating septal GABAergic cells during retrieval disinhibited parvalbumin-rich (PV+) cells in CA1. Direct activation of CA1 PV+ cells impaired memory and prevented the induction of extracellular signal–regulated kinase/mitogen-activated kinase signaling in postsynaptic pyramidal neurons. Opposing disinhibition of hippocampal PV+ cells reversibly restored memory. Our data indicate that suppression of feed-forward inhibition onto CA1 by septal GABAergic neurons is an important mechanism in gating contextual fear behavior.
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Hou, Xueqin, Cuiping Rong, Fugang Wang, Xiaoqian Liu, Yi Sun, and Han-Ting Zhang. "GABAergic System in Stress: Implications of GABAergic Neuron Subpopulations and the Gut-Vagus-Brain Pathway." Neural Plasticity 2020 (August 1, 2020): 1–11. http://dx.doi.org/10.1155/2020/8858415.
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Stress can cause a variety of central nervous system disorders, which are critically mediated by the γ-aminobutyric acid (GABA) system in various brain structures. GABAergic neurons have different subsets, some of which coexpress certain neuropeptides that can be found in the digestive system. Accumulating evidence demonstrates that the gut-brain axis, which is primarily regulated by the vagus nerve, is involved in stress, suggesting a communication between the “gut-vagus-brain” pathway and the GABAergic neuronal system. Here, we first summarize the evidence that the GABAergic system plays an essential role in stress responses. In addition, we review the effects of stress on different brain regions and GABAergic neuron subpopulations, including somatostatin, parvalbumin, ionotropic serotonin receptor 5-HT3a, cholecystokinin, neuropeptide Y, and vasoactive intestinal peptide, with regard to signaling events, behavioral changes, and pathobiology of neuropsychiatric diseases. Finally, we discuss the gut-brain bidirectional communications and the connection of the GABAergic system and the gut-vagus-brain pathway.
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Zhu, Ping Jun, and Vincent A. Chiappinelli. "Nicotine Modulates Evoked GABAergic Transmission in the Brain." Journal of Neurophysiology 82, no. 6 (December 1, 1999): 3041–45. http://dx.doi.org/10.1152/jn.1999.82.6.3041.
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The effects of nicotine on evoked GABAergic synaptic transmission were examined using whole cell recordings from neurons of the lateral spiriform nucleus in embryonic chick brain slices. All synaptic activities were abolished by the GABAA receptor antagonist, bicuculline (20 μM). Under voltage-clamp with KCl-filled pipettes (holding potential −70 mV), nicotine (0.1–1.0 μM) increased the frequency of spontaneous GABAergic currents in a dose-dependent manner. Nicotine enhanced electrically evoked GABAergic transmission only at relatively low concentrations of 50–100 nM (but not 25 nM), which approximate the concentrations of nicotine in the blood produced by cigarette smoking. At higher concentrations nicotine had either no effect (0.25 μM) or diminished (0.5–1.0 μM) evoked GABAergic neurotransmission. Nicotine had no significant effect on the postsynaptic current induced by exogenous GABA (30–50 μM). These data imply that nicotine levels attained in smokers are sufficient to enhance evoked GABAergic transmission in the brain, and that this effect is most likely mediated through activation of presynaptic nicotinic receptors.
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Yan, Fenxia, Zilong Gao, Pin Chen, Li Huang, Dangui Wang, Na Chen, Ruixiang Wu, et al. "Coordinated Plasticity between Barrel Cortical Glutamatergic and GABAergic Neurons during Associative Memory." Neural Plasticity 2016 (2016): 1–20. http://dx.doi.org/10.1155/2016/5648390.
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Neural plasticity is associated with memory formation. The coordinated refinement and interaction between cortical glutamatergic and GABAergic neurons remain elusive in associative memory, which we examine in a mouse model of associative learning. In the mice that show odorant-induced whisker motion after pairing whisker and odor stimulations, the barrel cortical glutamatergic and GABAergic neurons are recruited to encode the newly learnt odor signal alongside the innate whisker signal. These glutamatergic neurons are functionally upregulated, and GABAergic neurons are refined in a homeostatic manner. The mutual innervations between these glutamatergic and GABAergic neurons are upregulated. The analyses by high throughput sequencing show that certain microRNAs related to regulating synapses and neurons are involved in this cross-modal reflex. Thus, the coactivation of the sensory cortices through epigenetic processes recruits their glutamatergic and GABAergic neurons to be the associative memory cells as well as drive their coordinated refinements toward the optimal state for the storage of the associated signals.
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Hristova, Katerina, Cristina Martinez-Gonzalez, Thomas C. Watson, Neela K. Codadu, Kevan Hashemi, Peter C. Kind, Matthew F. Nolan, and Alfredo Gonzalez-Sulser. "Medial septal GABAergic neurons reduce seizure duration upon optogenetic closed-loop stimulation." Brain 144, no. 5 (March 26, 2021): 1576–89. http://dx.doi.org/10.1093/brain/awab042.
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Abstract Seizures can emerge from multiple or large foci in temporal lobe epilepsy, complicating focally targeted strategies such as surgical resection or the modulation of the activity of specific hippocampal neuronal populations through genetic or optogenetic techniques. Here, we evaluate a strategy in which optogenetic activation of medial septal GABAergic neurons, which provide extensive projections throughout the hippocampus, is used to control seizures. We utilized the chronic intrahippocampal kainate mouse model of temporal lobe epilepsy, which results in spontaneous seizures and as is often the case in human patients, presents with hippocampal sclerosis. Medial septal GABAergic neuron populations were immunohistochemically labelled and were not reduced in epileptic conditions. Genetic labelling with mRuby of medial septal GABAergic neuron synaptic puncta and imaging across the rostral to caudal extent of the hippocampus, also indicated an unchanged number of putative synapses in epilepsy. Furthermore, optogenetic stimulation of medial septal GABAergic neurons consistently modulated oscillations across multiple hippocampal locations in control and epileptic conditions. Finally, wireless optogenetic stimulation of medial septal GABAergic neurons, upon electrographic detection of spontaneous hippocampal seizures, resulted in reduced seizure durations. We propose medial septal GABAergic neurons as a novel target for optogenetic control of seizures in temporal lobe epilepsy.
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Brunskine, Cindy, Stefan Passlick, and Christian Henneberger. "Structural Heterogeneity of the GABAergic Tripartite Synapse." Cells 11, no. 19 (October 7, 2022): 3150. http://dx.doi.org/10.3390/cells11193150.
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The concept of the tripartite synapse describes the close interaction of pre- and postsynaptic elements and the surrounding astrocyte processes. For glutamatergic synapses, it is established that the presence of astrocytic processes and their structural arrangements varies considerably between and within brain regions and between synapses of the same neuron. In contrast, less is known about the organization of astrocytic processes at GABAergic synapses although bi-directional signaling is known to exist at these synapses too. Therefore, we established super-resolution expansion microscopy of GABAergic synapses and nearby astrocytic processes in the stratum radiatum of the mouse hippocampal CA1 region. By visualizing the presynaptic vesicular GABA transporter and the postsynaptic clustering protein gephyrin, we documented the subsynaptic heterogeneity of GABAergic synaptic contacts. We then compared the volume distribution of astrocytic processes near GABAergic synapses between individual synapses and with glutamatergic synapses. We made two novel observations. First, astrocytic processes were more abundant at the GABAergic synapses with large postsynaptic gephyrin clusters. Second, astrocytic processes were less abundant in the vicinity of GABAergic synapses compared to glutamatergic, suggesting that the latter may be selectively approached by astrocytes. Because of the GABA transporter distribution, we also speculate that this specific arrangement enables more efficient re-uptake of GABA into presynaptic terminals.
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Petukhova, Elena, Daria Ponomareva, Karin Rustler, Burkhard Koenig, and Piotr Bregestovski. "Action of the Photochrome Glyght on GABAergic Synaptic Transmission in Mouse Brain Slices." International Journal of Molecular Sciences 23, no. 18 (September 12, 2022): 10553. http://dx.doi.org/10.3390/ijms231810553.
Full textAbstract:
Glyght is a new photochromic compound described as an effective modulator of glycine receptors at heterologous expression, in brain slices and in zebrafish larvae. Glyght also caused weak inhibition of GABAA-mediated currents in a cell line expressing α1/β2/γ2 GABAA receptors. However, the effects of Glyght on GABAergic transmission in the brain have not been analysed, which does not allow a sufficiently comprehensive assessment of the effects of the compound on the nervous system. Therefore, in this study using whole-cell patch-clamp recording, we analysed the Glyght (100 µM) action on evoked GABAergic inhibitory postsynaptic currents (eIPSCs) in mice hippocampal slices. Two populations of cells were found: the first responded by reducing the GABAergic eIPSCs’ amplitude, whereas the second showed no sensitivity to the compound. Glyght did not affect the ionic currents’ amplitude induced by GABA application, suggesting the absence of action on postsynaptic GABA receptors. Additionally, Glyght had no impact on the paired-pulse modulation of GABAergic eIPSCs, indicating that Glyght does not modulate the neurotransmitter release mechanisms. In the presence of strychnine, an antagonist of glycine receptors, the Glyght effect on GABAergic synaptic transmission was absent. Our results suggest that Glyght can modulate GABAergic synaptic transmission via action on extrasynaptic glycine receptors.
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Provenzano, Giovanni, Angela Gilardoni, Marika Maggia, Mattia Pernigo, Paola Sgadò, Simona Casarosa, and Yuri Bozzi. "Altered Expression of GABAergic Markers in the Forebrain of Young and Adult Engrailed-2 Knockout Mice." Genes 11, no. 4 (April 1, 2020): 384. http://dx.doi.org/10.3390/genes11040384.
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Impaired function of GABAergic interneurons, and the subsequent alteration of excitation/inhibition balance, is thought to contribute to autism spectrum disorders (ASD). Altered numbers of GABAergic interneurons and reduced expression of GABA receptors has been detected in the brain of ASD subjects and mouse models of ASD. We previously showed a reduced expression of GABAergic interneuron markers parvalbumin (PV) and somatostatin (SST) in the forebrain of adult mice lacking the Engrailed2 gene (En2-/- mice). Here, we extended this analysis to postnatal day (P) 30 by using in situ hybridization, immunohistochemistry, and quantitative RT-PCR to study the expression of GABAergic interneuron markers in the hippocampus and somatosensory cortex of En2-/- and wild type (WT) mice. In addition, GABA receptor subunit mRNA expression was investigated by quantitative RT-PCR in the same brain regions of P30 and adult En2-/- and WT mice. As observed in adult animals, PV and SST expression was decreased in En2-/- forebrain of P30 mice. The expression of GABA receptor subunits (including the ASD-relevant Gabrb3) was also altered in young and adult En2-/- forebrain. Our results suggest that GABAergic neurotransmission deficits are already evident at P30, confirming that neurodevelopmental defects of GABAergic interneurons occur in the En2 mouse model of ASD.
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Chen, Xin, Hain-Ann Hsueh, Kenneth Greenberg, and Frank S. Werblin. "Three Forms of Spatial Temporal Feedforward Inhibition Are Common to Different Ganglion Cell Types in Rabbit Retina." Journal of Neurophysiology 103, no. 5 (May 2010): 2618–32. http://dx.doi.org/10.1152/jn.01109.2009.
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There exist more than 30 different morphological amacrine cell types, but there may be fewer physiological types. Here we studied the amacrine cell outputs by measuring the temporal and spatial properties of feedforward inhibition to four different types of ganglion cells. These ganglion cells, each with concentric receptive field organization, appear to receive a different relative contribution of the same three forms of feed-forward inhibition, namely: local glycinergic, local sustained GABAergic, and broad transient GABAergic inhibition. Two of these inhibitory components, local glycinergic inhibition and local sustained GABAergic inhibition were localized to narrow regions confined to the dendritic fields of the ganglion cells. The third, a broad transient GABAergic inhibition, was driven from regions peripheral to the dendritic area. Each inhibitory component is also correlated with characteristic kinetics expressed in all ganglion cells: broad transient GABAergic inhibition had the shortest latency, local glycinergic inhibition had an intermediate latency, and local sustained GABAergic inhibition had the longest latency. We suggest each of these three inhibitory components represents the output from a distinct class of amacrine cell, mediates a specific visual function, and each forms a basic functional component for the four ganglion cell types. Similar subunits likely exist in the circuits of other ganglion cell types as well.
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Grattan, D. R., and M. Selmanoff. "Prolactin- and testosterone-induced inhibition of LH secretion after orchidectomy: role of preoptic and tuberoinfundibular γ-aminobutyric acidergic neurones." Journal of Endocrinology 143, no. 1 (October 1994): 165–74. http://dx.doi.org/10.1677/joe.0.1430165.
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Abstract The inhibitory amino acid neurotransmitter γ-amino-butyric acid (GABA) may play an important role in the regulation of LH-releasing hormone secretion. The present study examined the effect of prolactin on GABAergic neuronal activity in microdissected brain regions of the orchidectomized rat, to determine whether inhibition of LH secretion after castration by acute hyperprolactinaemia was associated with prolactin-induced changes in GABAergic neuronal activity. The effects of prolactin were contrasted with the effects of testosterone on hypothalamic GABAergic neurones after orchidectomy. GABA concentrations were measured by high pressure liquid chromatography in eight microdissected brain regions in untreated rats and 60 min after inhibition of the GABA catabolic enzyme GABA transaminase by injection of amino-oxyacetic acid (AOAA). The rate of GABA accumulation in microdissected brain regions following injection of AOAA was taken as an index of GABAergic neuronal activity. Rats were divided into seven experimental groups: intact controls, 2 days after castration, 2 days after castration with prolactin treatment (2·5 mg ovine prolactin injected s.c. every 12 h, starting at the time of castration), 2 days after castration with testosterone replacement (30 mm silicone elastomer implant containing crystalline testosterone), 6 days after castration, 6 days after castration with prolactin treatment, and 6 days after castration with testosterone replacement. Both 2 and 6 days after castration, plasma LH was markedly elevated above levels in intact rats, and AOAA-induced GABA accumulation was significantly decreased in the diagonal band of Broca at the level of the organum vasculosum of the lamina terminalis, in the medial preoptic nucleus and in the median eminence. Hyperprolactinaemia significantly reduced LH levels 2 days but not 6 days after castration. GABAergic neuronal activity, however, was not significantly affected by prolactin at either time. Testosterone replacement blocked the postcastration elevation in plasma LH and prevented the castration-induced suppression of GABAergic neuronal activity both 2 and 6 days after castration. There were no castration- or hormone-induced changes in GABAergic neurones observed in the medical or lateral septum, caudate nucleus, cingulate cortex or arcuate nucleus. These results demonstrate that the activity of GABAergic neurones terminating in the rostral hypothalamus and the median eminence is positively regulated by testosterone, and that these steroid-sensitive GABAergic neurones may be important in the negative-feedback control of LH secretion. Inhibition of LH secretion by hyperprolactinaemia, however, may not be mediated by changes in GABAergic neuronal activity. Journal of Endocrinology (1994) 143, 165–174
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Kawaguchi, Yasuo. "Cortical GABAergic Neural Circuits." Brain & Neural Networks 5, no. 4 (1998): 171–77. http://dx.doi.org/10.3902/jnns.5.171.
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