GABAergic

About: GABAergic is a research topic. Over the lifetime, 9595 publications have been published within this topic receiving 473568 citations.

Brain-derived neurotrophic factor modulates fast synaptic inhibition by regulating GABA(A) receptor phosphorylation, activity, and cell-surface stability.

Abstract: The efficacy of GABAergic synaptic inhibition is a principal factor in controlling neuronal activity. We demonstrate here that brain-derived neurotrophic factor modulates the activity of GABA A receptors, the main sites of fast synaptic inhibition in the brain, within minutes of application. Temporally, this comprised an early enhancement in the miniature IPSC amplitude, followed by a prolonged depression. This modulation was concurrent with enhanced PKC-mediated phosphorylation, followed by protein phosphatase 2A (PP2A)-mediated dephosphorylation of the GABA A receptor. Mechanistically, these events were facilitated by differential recruitment of PKC, receptor for activated C-kinase, and PP2A to GABA A receptors, depending on the phosphorylation state of the receptor β 3 -subunit. Thus, transient formation of GABA A receptor signaling complexes has the potential to provide a basis for acute changes in receptor function underlying GABAergic synaptic plasticity.

Calcium-binding proteins as markers for subpopulations of GABAergic neurons in monkey striate cortex

Abstract: Recent studies have shown that the presence of immunoreactivity for parvalbumin (PV-IR) and calbindin-D 28k (Cal-IR) can be used as markers for certain types of gamma-aminobutyric acid (GABA) immunoreactive interneurons in monkey cerebral cortex. Little quantitative information is available regarding the features that distinguish these two subpopulations, however. Therefore, in this study we localized PV-IR and Cal-IR neurons in Macaca monkey striate cortex and analyzed quantitatively their laminar distribution, cell morphology, and co-localization with GABA by double-labeling immunocytochemistry. PV-IR was found in nonpyramidal cells in all layers of the cortex, although PV-IR cells in layer 1 were rare. In contrast, Cal-IR was found mainly in nonpyramidal cells in two bands corresponding to layers 2-3 and 5-6. We found very few double-labeled PV-IR/Cal-IR cells but confirmed that almost all PV-IR and Cal-IR cells are GABAergic. Overall, 74% of GABA neurons in striate cortex displayed PV-IR compared to only 12% that displayed Cal-IR and 14% that were GABA-IR only. Quantitative analysis indicated that the relative proportion of GABA cells that displayed PV-IR or Cal-IR showed conspicuous laminar differences, which were often complementary. Cell size measurements indicated that PV-IR/GABA cells in layers 2-3 and 5-6 were significantly larger than Cal-IR/GABA cells. Analysis of the size, shape, and orientation of stained cell bodies and proximal dendrites further demonstrated that each subpopulation contained several different types of smooth stellate cells, suggesting that Cal-IR and PV-IR are found in functionally and morphologically heterogeneous subpopulations of GABA neurons. There was a thick bundle of PV-IR axons in the white matter underlying the striate but not prestriate cortex. PV-IR punctate labeling matched the cytochrome oxidase staining pattern in layers 4A and 4C, suggesting that PV-IR is present in geniculocortical afferents as well as intrinsic neurons. Cal-IR neuropil staining was high in layers 1, 2, 4B, and 5, where cytochrome oxidase staining is relatively low. We did not find a preferential localization of either PV-IR or Cal-IR cell bodies in any cytochrome oxidase compartments in layers 2-3 of the cortex. These findings indicate that PV and Cal are distributed into different neuronal circuits.

Fast IPSPs elicited via multiple synaptic release sites by different types of GABAergic neurone in the cat visual cortex.

Abstract: 1. The effects of synapses established by smooth dendritic neurones on pyramidal and spiny stellate cells were studied in areas 17 and 18 of the cat visual cortex in vitro. Paired intracellular recordings with biocytin-filled electrodes and subsequent light and electron microscopic analysis were used to determine the sites of synaptic interaction. 2. All smooth dendritic cells established type II synapses previously shown to be made by terminals containing GABA, therefore the studied cells are probably GABAergic. Three classes of presynaptic cell could be defined, based on their efferent synaptic target preference determined from random samples of unlabelled postsynaptic cells. (a) Basket cells (n = 6) innervated mainly somata (49.9 +/- 13.8%) and dendritic shafts (45.2 +/- 10.7%) and, to a lesser extent, dendritic spines (4.9 +/- 4.6%). (b) Dendrite-targeting cells (n = 5) established synapses predominantly on dendritic shafts (84.3 +/- 9.4%) and less frequently on dendritic spines (11.2 +/- 6.7%) or somata (4.5 +/- 4.7%). (c) Double bouquet cells (n = 4) preferred dendritic spines (69.2 +/- 4.2%) to dendritic shafts (30.8 +/- 4.2%) as postsynaptic targets and avoided somata. 3. Interneurones formed 5240 +/- 1600 (range, 2830-9690) synaptic junctions in the slices. Based on the density of synapses made by single interneurones and the volume density of GABAergic synapses, it was calculated that an average interneurone provides 0.66 +/- 0.20% of the GABAergic synapses in its axonal field. 4. The location of synaptic junctions on individual, identified postsynaptic cells reflected the overall postsynaptic target distribution of the same GABAergic neurone. The number of synaptic junctions between pairs of neurones could not be predicted from light microscopic examination. The number of electron microscopically verified synaptic sites was generally smaller for the dendritic domain and larger for the somatic domain than expected from light microscopy. All presynaptic cells established multiple synaptic junctions on their postsynaptic target cells. A basket cell innervated a pyramidal cell via fifteen release sites; the numbers of synapses formed by three dendrite-targeting cells on pyramidal cells were seventeen and eight respectively, and three on a spiny stellate cell; the interaction between a double bouquet cell and a postsynaptic pyramidal cell was mediated by ten synaptic junctions. 5. All three types of interneurone (n = 6; 2 for each type of cell) elicited short-latency IPSPs with fast rise time (10-90%; 2.59 +/- 1.02 ms) and short duration (at half-amplitude, 15.82 +/- 5.24 ms), similar to those mediated by GABAA receptors. 6. Average amplitudes of unitary IPSPs (n = 6) were 845 +/- 796 microV (range, 134-2265 microV). Variability of IPSP amplitude was moderate, the average ratio of IPSP and baseline noise variance was 1.54 +/- 0.96. High frequency activation of single presynaptic dendrite-targeting cells led to an initial summation followed by use-dependent depression of the averaged postsynaptic response. Double bouquet cell-evoked IPSPs, recorded in the soma, had a smaller amplitude than those evoked by the other two cell types. In all connections, transmission failures were rare or absent, particularly when mediated by a high number of release sites. 7. The results demonstrate that different types of neocortical GABAergic neurones innervate distinct domains on the surface of their postsynaptic target cells. Nevertheless, all three types of cell studied here elicit fast IPSPs and provide GABAergic input through multiple synaptic release sites with few, if any, failures of transmission.