GABAergic

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

Ultrastructural identification of somata and neural processes immunoreactive to antibodies against glutamic acid decarboxylase (GAD) in the dorsal lateral geniculate nucleus of the cat

Abstract: The cat dorsal lateral geniculate nucleus (LGN) was examined at the light- and electron-microscopic level after immunocytochemistry for GAD (the synthesizing enzyme of the inhibitory neurotransmitter GABA), to identify cells and processes with GAD-like immunoreactivity. GAD-positive perikarya were distributed throughout the A and C laminae, constituting a moderate proportion of cells in the LGN. Labeled cells were characterized by small size, scant cytoplasm, relatively large nuclei with common indentations, small mitochondria, few organelles and few strands of rough endoplasmic reticulum. Unlabeled cells were of large, medium and small size. GAD-positive terminals were identified as F1 and F2 types (Guillery's nomenclature) on the basis of their synaptic relations and ultrastructure. Labeled F2 terminals were postsynaptic to retinal (RLP) boutons and presynaptic to unlabeled dendrites in synaptic glomeruli. Labeled F1 terminals made synapses on unlabeled somata and dendrites, and on labeled dendrites and F2 terminals. Presumably, most labeled F1 terminals originate from GABAergic perigeniculate axons. Retinal (RLP) and cortico-geniculate (RSD) boutons remained unlabeled in the reative zone. These terminals made synapses with labeled and unlabeled dendrites and with labeled F2 boutons. In conjunction with previous studies on GAD-positive cells in the perigeniculate nucleus, these results provide immunocytochemical and morphological evidence suggesting that the GABAergic intrinsic and extrinsic (perigeniculate) interneurons mediate the different inhibitory phenomena which occur in relay cells of the cat LGN. The ultrastructural features and synaptic relations of GABAergic cells and processes in the cat LGN are similar to those of equivalent neural elements in the LGN of rat and monkey, suggesting general principles of organization and morphology for GABAergic neurons in the thalamus of different mammals.

A Dynamic Role for GABA Receptors on the Firing Pattern of Midbrain Dopaminergic Neurons

Abstract: Dopaminergic neurons are subject to a significant background GABAergic input in vivo. The presence of this GABAergic background might be expected to inhibit dopaminergic neuron firing. However, dopaminergic neurons are not all silent but instead fire in single-spiking and burst firing modes. Here we present evidence that phasic changes in the tonic activity of GABAergic afferents are a potential extrinsic mechanism that triggers bursts and pauses in dopaminergic neurons. We find that spontaneous single-spiking is more sensitive to activation of GABA receptors than phasic N-methyl-D-aspartate (NMDA)-mediated burst firing in rat slices (P15-P31). Because tonic activation of GABA(A) receptors has previously been shown to suppress burst firing in vivo, our results suggest that the activity patterns seen in vivo are the result of a balance between excitatory and inhibitory conductances that interact with the intrinsic pacemaking currents observed in slices. Using the dynamic clamp technique, we applied balanced, constant NMDA and GABA(A) receptor conductances into dopaminergic neurons in slices. Bursts could be produced by disinhibition (phasic removal of the GABA(A) receptor conductance), and these bursts had a higher frequency than bursts produced by the same NMDA receptor conductance alone. Phasic increases in the GABA(A) receptor conductance evoked pauses in firing. In contrast to NMDA receptor, application of constant AMPA and GABA(A) receptor conductances caused the cell to go into depolarization block. These results support a bidirectional mechanism by which GABAergic inputs, in balance with NMDA receptor-mediated excitatory inputs, control the firing pattern of dopaminergic neurons.

Metabotropic Glutamate Receptor 5 Upregulation in Children with Autism is Associated with Underexpression of Both Fragile X Mental Retardation Protein and GABAA Receptor Beta 3 in Adults with Autism

Abstract: Recent work has demonstrated the impact of dysfunction of the GABAergic signaling system in brain and the resultant behavioral pathologies in subjects with autism. In animal models, altered expression of Fragile X mental retardation protein (FMRP) has been linked to downregulation of GABA receptors. Interestingly, the autistic phenotype is also observed in individuals with Fragile X syndrome. This study was undertaken to test previous theories relating abnormalities in levels of FMRP to GABA(A) receptor underexpression. We observed a significant reduction in levels of FMRP in the vermis of adults with autism. Additionally, we found that levels of metabotropic glutamate receptor 5 (mGluR5) protein were significantly increased in vermis of children with autism versus age and postmortem interval matched controls. There was also a significant decrease in level of GABA(A) receptor beta 3 (GABRβ3) protein in vermis of adult subjects with autism. Finally, we found significant increases in glial fibrillary acidic protein in vermis of both children and adults with autism when compared with controls. Taken together, our results provide further evidence that altered FMRP expression and increased mGluR5 protein production potentially lead to altered expression of GABA(A) receptors.

Increased GABAergic function in mouse models of Huntington's disease: reversal by BDNF

Abstract: Huntington's disease (HD) is characterized by loss of striatal gamma-aminobutyric acid (GABA)ergic medium-sized spiny projection neurons (MSSNs), whereas some classes of striatal interneurons are relatively spared. Striatal interneurons provide most of the inhibitory synaptic input to MSSNs and use GABA as their neurotransmitter. We reported previously alterations in glutamatergic synaptic activity in the R6/2 and R6/1 mouse models of HD. In the present study, we used whole-cell voltage clamp recordings to examine GABAergic synaptic currents in MSSNs from striatal slices in these two mouse models compared to those in age-matched control littermates. The frequency of spontaneous GABAergic synaptic currents was increased significantly in MSSNs from R6/2 transgenics starting around 5-7 weeks (when the overt behavioral phenotype begins) and continuing in 9-14-week-old mice. A similar increase was observed in 12-15-month-old R6/1 transgenics. Bath application of brain-derived neurotrophic factor, which is downregulated in HD, significantly reduced the frequency of spontaneous GABAergic synaptic currents in MSSNs from R6/2 but not control mice at 9-14 weeks. Increased GABA current densities also occurred in acutely isolated MSSNs from R6/2 animals. Immunofluorescence demonstrated increased expression of the ubiquitous alpha1 subunit of GABA(A) receptors in MSSNs from R6/2 animals. These results indicate that increases in spontaneous GABAergic synaptic currents and postsynaptic receptor function occur in parallel to progressive decreases in glutamatergic inputs to MSSNs. In conjunction, both changes will severely alter striatal outputs to target areas involved in the control of movement.