GABAergic

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

Distribution of GABAergic neurons and axon terminals in the macaque striate cortex

Abstract: Antisera to glutamic acid decarboxylase (GAD) and γ-aminobutyric acid (GABA) have been used to characterize the morphology and distribution of presumed GABAergic neurons and axon terminals within the macaque striate cortex. Despite some differences in the relative sensitivity of these antisera for detecting cell bodies and terminals, the overall patterns of labeling appear quite similar. GABAergic axon terminals are particularly prominent in zones known to receive the bulk of the projections from the lateral geniculate nucleus; laminae 4C, 4A, and the cytochrome-rich patches of lamina 3. In lamina 4A, GABAergic terminals are distributed in a honeycomb pattern which appears to match closely the spatial pattern of geniculate terminations in this region. Quantitative analysis of axon terminals that contain flat vesicles and form symmetric synaptic contacts (FS terminals) in lamina 4Cβ and in lamina 5 suggest that the prominence of GAD and GABA axon terminal labeling in the geniculate recipient zones is due, at least in part, to the presence of larger GABAergic axon terminals in these regions. GABAergic cell bodies and their initial dendritic segments display morphological features characteristic of nonpyramidal neurons and are found in all layers of striate cortex. The density of GAD and GABA immunoreactive neurons is greatest in laminae 2–3A, 4A, and 4Cβ. The distribution of GABAergic neurons within lamina 3 does not appear to be correlated with the patchy distribution of cytochrome oxidase in this region; i.e., there is no significant difference in the density of GAD and GABA immunoreactive neurons in cytochrome-rich and cytochrome-poor regions of lamina 3. Counts of labeled and unlabeled neurons indicate that GABA immunoreactive neurons make up at least 15% of the neurons in striate cortex. Layer 1 is distinct from the other cortical layers by virtue of its high percentage (77–81%) of GABAergic neurons. Among the other layers, the proportion of GABAergic neurons varies from roughly 20% in laminae 2–3A to 12% in laminae 5 and 6. Finally, there are conspicuous laminar differences in the size and dendritic arrangement of GAD and GABA immunoreactive neurons. Lamina 4Cα and lamina 6 are distinguished from the other layers by the presence of populations of large GABAergic neurons, some of which have horizontally spreading dendritic processes. GABAergic neurons within the superficial layers are significantly smaller and the majority appear to have vertically oriented dendritic processes. These results provide support for the idea that GABAergic neurons make up a significant proportion of the neurons within the macaque striate cortex and that there are laminar differences in the number and the types of GABAergic neurons—differences that may be relevant for understanding the contributions of GABA-mediated inhibition to striate cortex function.

Functional correlation of GABA(A) receptor alpha subunits expression with the properties of IPSCs in the developing thalamus.

Abstract: GABAA receptor α1 and α2 subunits are expressed differentially with ontogenic period in the brain, but their functional roles are not known. We have recorded GABAAreceptor-mediated IPSCs from laterodorsal (LD) thalamic relay neurons in slices of rat brain at various postnatal ages and found that decay times of evoked IPSCs and spontaneous miniature IPSCs undergo progressive shortening during the first postnatal month. With a similar time course, expression of transcripts and proteins of GABAA receptor α2 subunit in LD thalamic region declined, being replaced by those of α1 subunit. To further address the causal relationship between α subunits and IPSC decay time kinetics, we have overexpressed GABAA receptor α1 subunit together with green fluorescent protein in LD thalamic neurons in organotypic culture using recombinant Sindbis virus vectors. Miniature IPSCs recorded from the LD thalamic neurons overexpressed with α1 subunit had significantly faster decay time compared with control expressed with β-galactosidase. We conclude that the α2-to-α1 subunit switch underlies the developmental speeding in the decay time of GABAergic IPSCs.

Developmental Up-Regulation of KCC2 in the Absence of GABAergic and Glutamatergic Transmission

Abstract: Postsynaptic gamma-aminobutyric acid (GABA)A-mediated responses switch from depolarizing to hyperpolarizing during postnatal development of the rodent hippocampus. This is attributable to a decrease in the concentration of intracellular chloride set by the expression of the neuron-specific K+-Cl- co-transporter, KCC2. A recent in vitro study [Ganguly et al. (2001) Cell, 105, 521-532] showed that KCC2 expression may be under the trophic control of GABAA receptor-mediated transmission. Here we have studied the developmental expression of KCC2 protein in mouse hippocampal dissociated cultures as well as organotypic cultures. A low somatic expression level was found in neurons prior to the formation of the first synapses, as detected by synaptophysin immunoreactivity. Thereafter, KCC2 expression was strongly up-regulated during neuronal maturation. The developmental up-regulation of KCC2 expression was not altered by a chronic application (throughout the culturing period; 2-15 days in vitro) of the action-potential blocker TTX or the N-methyl-d-aspartate (NMDA) and non-NMDA antagonists APV and NBQX. Blockade of GABAA-mediated transmission with picrotoxin did not affect the expression levels of KCC2 protein either. These data show that neither neuronal spiking nor ionotropic glutamatergic and GABAergic transmission are required for the developmental expression of KCC2 in mouse hippocampal neurons in vitro.

mRNA and Protein Levels for GABAAα4, α5, β1 and GABABR1 Receptors are Altered in Brains from Subjects with Autism

Abstract: We have shown altered expression of gamma-aminobutyric acid A (GABAA) and gamma-aminobutyric acid B (GABAB) receptors in the brains of subjects with autism. In the current study, we sought to verify our western blotting data for GABBR1 via qRT-PCR and to expand our previous work to measure mRNA and protein levels of 3 GABAA subunits previously associated with autism (GABRα4; GABRα5; GABRβ1). Three GABA receptor subunits demonstrated mRNA and protein level concordance in superior frontal cortex (GABRα4, GABRα5, GABRβ1) and one demonstrated concordance in cerebellum (GABΒR1). These results provide further evidence of impairment of GABAergic signaling in autism.