Long-term plasticity at GABAergic and glycinergic synapses: mechanisms and functional significance

Gaı̈arsa, Jean-Luc; Caillard, Olivier; Ben‐Ari, Yehezkel

doi:10.1016/s0166-2236(02)02269-5

Cited by 274 publications

(212 citation statements)

References 62 publications

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“…1 GABA A receptors are the ubiquitous ligand-gated chloride ionophores responsible for most rapid inhibition within the central nervous system. [2][3][4] Within the NTS, activation of GABA A receptors inhibits virtually all neurons tested and results in an increase in arterial pressure, heart rate, and sympathetic outflow, effects consistent with inhibitory modulation of arterial baroreceptor reflexes. 1 The function of GABA A receptors has been shown to be modulated by a variety of factors.…”

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confidence: 67%

“…In response to other perturbations, GABA A receptors have been shown to undergo changes in subunit composition, changes in the number and/or affinity of binding sites, and changes in intracellular calcium and/or phosphorylation state leading to enhanced or reduced conductance. 3,4 All of these possibilities remain avenues for future studies.…”

Section: Discussionmentioning

confidence: 99%

“…Receptor number, subunit composition, and phosphorylation state are but a few of the ways that GABA receptor function can be altered after chronic exposure to alcohol, barbiturates, benzodiazepines, and GABA itself. [2][3][4] Alterations in the responses of NTS neurons to GABA A receptor activation could result in alterations in the integration of afferent inputs, reflex function, and resting cardiovascular parameters. The goal of the current study was to determine if the responses of isolated NTS neurons to activation of GABA A receptors are altered in hypertension.…”

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confidence: 99%

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Responses to GABAA receptor activation are altered in NTS neurons isolated from chronic hypoxic rats

2004

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Abstract-The inhibitory amino acid GABA is a potent modulator of the spontaneous discharge and the responses to afferent inputs of neurons in the nucleus of the solitary tract (NTS). To determine if responses to activation of GABA A receptors are altered in hypertension, GABA A receptor-evoked whole cell currents were measured in enzymatically dispersed NTS neurons from 33 normotensive (NT, 109Ϯ4 mm Hg, nϭ7) and 24 hypertensive (HT, 167Ϯ5 mm Hg, nϭ24) rats. GABA A receptor-evoked currents reversed at the calculated equilibrium potential for chloride and were blocked by bicuculline (nϭ6). Membrane capacitance was the same in neurons from NT (7.5Ϯ0.6 pF, nϭ62) and HT (6.8Ϯ0.6 pF, nϭ51) rats. The EC 50 for peak GABA-evoked currents cells was significantly greater in neurons from HT (21.0Ϯ2.6 mol/L, nϭ16) compared with NT rats (13.0Ϯ1.8 mol/L, nϭ14, Pϭ0.01). The EC 50 of neurons exhibiting DiA labeling of presumptive aortic nerve terminals was no different than that observed in the nonlabeled cells (19.0Ϯ4.9 mol/L, nϭ4). The time constant for desensitization of GABA A -evoked currents was the same in neurons from HT (4.5Ϯ0.3 seconds, nϭ17) and NT rats (3.8Ϯ0.3 seconds, nϭ17, PϾ0.05). Repetitive pulse application of GABA revealed a more rapid decline in the evoked current in neurons from HT compared with NT rats. The amplitude of the 5th pulse of GABA (5-second duration, 2-second interval) was 21Ϯ2% the amplitude of the 1st pulse in NT rats (nϭ10) and 14Ϯ2% in HT rats (nϭ11, PϽ0.05). These alterations in GABA A -receptor evoked currents could render the neurons less sensitive to GABA A receptor inhibition and influence afferent integration by NTS neurons in HT. [2][3][4] Within the NTS, activation of GABA A receptors inhibits virtually all neurons tested and results in an increase in arterial pressure, heart rate, and sympathetic outflow, effects consistent with inhibitory modulation of arterial baroreceptor reflexes. 1 The function of GABA A receptors has been shown to be modulated by a variety of factors. Receptor number, subunit composition, and phosphorylation state are but a few of the ways that GABA receptor function can be altered after chronic exposure to alcohol, barbiturates, benzodiazepines, and GABA itself. [2][3][4] Alterations in the responses of NTS neurons to GABA A receptor activation could result in alterations in the integration of afferent inputs, reflex function, and resting cardiovascular parameters. The goal of the current study was to determine if the responses of isolated NTS neurons to activation of GABA A receptors are altered in hypertension. Methods GeneralSuccessful experiments were performed on adult (1 to 3 months), male Sprague-Dawley rats (375 to 500 g, Charles River Laboratories or Harlan Sprague-Dawley Inc). Rats were housed 2 per cage in a fully accredited (Association for Assessment and Accreditation of Laboratory Animal Care and the United States Department of Agriculture) laboratory animal room with free access to food and water. All rats were given at least 1 week to acclimat...

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confidence: 67%

Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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Responses to GABAA receptor activation are altered in NTS neurons isolated from chronic hypoxic rats

2004

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“…83,84 Long-term memory appears to involve a change in the brain at the level of the synapse called synaptic plasticity. [85][86][87][88][89] At the molecular level, several factors are known to contribute to synaptic plasticity, including changes in the quantity of neurotransmitters released into a synapse and the response of the postsynaptic neuron to those neurotransmitters. 87,[90][91][92][93] Long-term potentiation (LTP), one of several phenomena underlying synaptic plasticity, is widely considered to be one of the major cellular mechanisms involved in learning and memory.…”

Section: General Anesthetics and The Neural Substrates Of Memorymentioning

confidence: 99%

Inhibition of learning and memory by general anesthetics

Wang

Orser

2010

Can J Anesth/J Can Anesth

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“…Far less is known about modifications of inhibitory synapses under similar conditions of activity, although inhibitory inputs play a crucial role in shaping the activity of neuronal networks (Cobb et al, 1995;Freund and Buzsaki, 1996;reviewed in Freund, 2003;Klausberger and Somogyi, 2008). Long-term changes of interneuron discharge and of inhibitory transmission associated with increased synaptic activity have been reported at various inhibitory synapses (Buzsaki and Eidelberg, 1982;Gaiarsa et al, 2002;Kullmann and Lamsa, 2007;Klausberger and Somogyi, 2008;Pelletier and Lacaille, 2008;McBain and Kauer, 2009;Nissen et al, 2010). The cellular and molecular mechanisms underlying these phenomena are however still poorly understood and rely on both pre-and postsynaptic modifications depending on the synapses under study.…”

Section: Introductionmentioning

confidence: 99%

Excitatory synaptic activity is associated with a rapid structural plasticity of inhibitory synapses on hippocampal CA1 pyramidal cells

et al. 2011

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This article appeared in a journal published by Elsevier. The attached copy is furnished to the author for internal non-commercial research and education use, including for instruction at the authors institution and sharing with colleagues.Other uses, including reproduction and distribution, or selling or licensing copies, or posting to personal, institutional or third party websites are prohibited. Synaptic activity, such as long-term potentiation (LTP), has been shown to induce morphological plasticity of excitatory synapses on dendritic spines through the spine head and postsynaptic density (PSD) enlargement and reorganization. Much less, however, is known about activity-induced morphological modifications of inhibitory synapses. Using an in vitro model of rat organotypic hippocampal slice cultures and electron microscopy, we studied activity-related morphological changes of somatic inhibitory inputs triggered by a brief oxygeneglucose deprivation (OGD) episode, a condition associated with a synaptic enhancement referred to as anoxic LTP and a structural remodeling of excitatory synapses. Threedimensional reconstruction of inhibitory axo-somatic synapses at different times before and after brief OGD revealed important morphological changes. The PSD area significantly and markedly increased at synapses with large and complex PSDs, but not at synapses with simple, macular PSDs. Activity-related changes of PSD size and presynaptic bouton volume developed in a strongly correlated manner. Analyses of single and serial sections further showed that the density of inhibitory synaptic contacts on the cell soma did not change within 1 h after OGD. In contrast, the proportion of the cell surface covered with inhibitory PSDs, as well as the complexity of these PSDs significantly increased, with less macular PSDs and more complex, segmented shapes. Together, these data reveal a rapid activity-related restructuring of somatic inhibitory synapses characterized by an enlargement and increased complexity of inhibitory PSDs, providing a new mechanism for a quick adjustment of the excitatoryeinhibitory balance. This article is part of a Special Issue entitled 'Synaptic Plasticity & Interneurons'.

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Long-term plasticity at GABAergic and glycinergic synapses: mechanisms and functional significance

Cited by 274 publications

References 62 publications

Responses to GABAA receptor activation are altered in NTS neurons isolated from chronic hypoxic rats

Responses to GABAA receptor activation are altered in NTS neurons isolated from chronic hypoxic rats

Inhibition of learning and memory by general anesthetics

Excitatory synaptic activity is associated with a rapid structural plasticity of inhibitory synapses on hippocampal CA1 pyramidal cells

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