The Vesicular GABA Transporter, VGAT, Localizes to Synaptic Vesicles in Sets of Glycinergic as Well as GABAergic Neurons

Chaudhry, Farrukh A.; Reimer, Richard J.; Bellocchio, Elizabeth E.; Danbolt, N; Osen, Kirsten K.; Edwards, Robert H.; Storm‐Mathisen, Jon

doi:10.1523/jneurosci.18-23-09733.1998

Cited by 563 publications

(528 citation statements)

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“…Conversely, the relative distribution of mRNA for the ve- sicular GABA transporter (VGAT) had not been analyzed in this way and, based on our results, appears to be a more specific molecular indicator of the inhibitory neuronal phenotype. These findings also are consistent with the immunoperoxidase localization of VGAT antigen to hippocampal interneuron perikarya (14).…”

Section: Discussionsupporting

confidence: 88%

Differential Expression of GABA and Glutamate‐receptor Subunits and Enzymes Involved in GABA Metabolism between Electrophysiologically Identified Hippocampal CA1 Pyramidal Cells and Interneurons

Telfeian¹,

Tseng

Baybis

et al. 2003

Epilepsia

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Summary: Purpose:The balance between synaptic excitation and inhibition within the hippocampus is critical for maintaining normal hippocampal function. Even mild reduction in inhibition or enhancement of excitation can produce seizures. Synaptic excitation is produced by pyramidal cells and granule cells, whereas inhibition is produced by a smaller number of interneurons. To understand how two subpopulations of these excitatory and inhibitory neurons are regulated at the molecular level, we analyzed specific mRNA expression profiles for receptors that are significantly involved in synaptic transmission and in the synthesis and storage of the principal inhibitory neurotransmitter, ␥-aminobutyric acid (GABA). Our hypothesis was that differences in gene expression between inhibitory and excitatory neurons in the rat hippocampus might point to specific new targets for seizure pharmacotherapy.Methods: We combined the techniques of (a) whole-cell patch clamping in rat hippocampal slices, (b) biocytin staining for cell identification, (c) single-cell mRNA amplification, and (d) small-scale cDNA microarray analysis to allow us to obtain expression profiles for candidate genes from identified CA1 pyramidal neurons and interneurons. Electrophysiologic and morphologic data and expression profiles were obtained from 12 stratum pyramidale and seven stratum radiatum cells.Results: Presumed inhibitory neurons expressed significantly more GAD65, GAD67, vGAT, GABA A -receptor ␣3, and N-methyl-D-aspartate (NMDA)-receptor IIB mRNA, and presumed excitatory neurons expressed more GABA A -receptor ␣1, and NMDA-receptor I mRNA.Conclusions: Differential expression of candidate neurotransmitter-receptor subunits distinguished CA1 pyramidal neurons from interneurons. These differences may indicate potential new targets for altering the balance of inhibition and excitation in the treatment of epilepsy. Key Words: mRNA-GABA-Hippocampus-Interneuron-Brain slice-Epilepsy.Hippocampal excitatory and inhibitory neurons differ from one another in a variety of features including morphology, action potential-firing characteristics, neurotransmitter choice, peptide composition, calcium-binding protein composition, neurotransmitter-receptor subunit expression, and neurotransmitter release mechanisms (1). There are likely to be many other fundamental differences between these two classes of neurons. In general, these differences have been detected when new techniques or reagents have become available and are then applied to neurons of interest, for example, immunohistochemistry with a new antibody, or molecular techniques to identify newly cloned receptors. It would be useful if a simultaneous identification of many of these phenotypic characteristics of inhibitory interneurons could be determined in a cell-type-specific manner. This would allow identification of the expression of genes of interest and unknown genes that subserve important functions in these neurons and could serve to establish a coordinated molecular phenotype of the neurons in quest...

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Section: Discussionsupporting

confidence: 88%

Differential Expression of GABA and Glutamate‐receptor Subunits and Enzymes Involved in GABA Metabolism between Electrophysiologically Identified Hippocampal CA1 Pyramidal Cells and Interneurons

Telfeian¹,

Tseng

Baybis

et al. 2003

Epilepsia

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“…1E). This staining pattern was identical to that in previous report (Chaudhry et al, 1998;Takamori et al, 2000). Preincubation of the primary antibody with the synthetic peptide completely abolished the staining (Fig.1F).…”

Section: Immunohistochemical Localization Of Gaba and Vgat In The Matsupporting

confidence: 91%

Extrasynaptic localization of GABA in the developing mouse cerebellum

Takayama

Inoue

2004

Neuroscience Research

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In the adult brain, γ-amino butyric acid (GABA) is synaptically released and mediates inhibitory transmission. Recent studies have revealed that GABA is a trophic factor for brain development. To reveal the distribution of GABA and its secretion mechanisms during brain development, we investigated the immunohistochemical localization of two molecules, GABA and vesicular GABA transporter (VGAT), which is a GABAergic vesicle protein, in the developing mouse cerebellum by means of newly developed antibodies.Furthermore, we tested the relationship between developmental changes in distribution of above two molecules in the presynapses and ontogeny of GABAergic synapses. GABAergic synapses were detected by immunohistochemistry for the GABA A receptor α1 subunit, which is an essential subunit for inhibitory synaptic transmission in the mature cerebellar cortex.Until postnatal day 7 (P7), GABA was localized throughout the GABAergic neurons, and VGAT accumulated at axon varicosities and growth cones, where the α1 subunit did not accumulate. After P10, both GABA and VGAT became confined to the terminal sites where the α1 subunit was localized. These results suggested that GABA was extrasynaptically released from axon varicosities and growth cones by vesicular secretion 'exocytosis' and from all parts of GABAergic neurons during the cerebellar development by non-vesicular secretion 'diacrine'.

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“…11 Vesicular GABA transporter maintains constant levels of inhibitory neurotransmitters g-aminobutyric acid and glycine in the synaptic vesicles. 12 Therefore, this downregulation may adversely influence the inhibitory synaptic transmission. However, possible changes in expression profiles of most ionic receptors after SCI have not been explored completely yet.…”

Section: Discussionmentioning

confidence: 99%

Differential expression of glycine receptor subunit messenger RNA in the rat following spinal cord injury

Esmaeili

Zaker

2010

Spinal Cord

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Study design: Spinal cord injury (SCI) results in alterations in the regulation of many genes that may influence neuronal death and the subsequent loss of motor function and neuropathic pain. The subtype expression mRNA levels of glycine receptors (GlyRs) after SCI are unknown. Methods: Using real-time reverse transcription PCR, this study analyzed changes in the mRNA abundance of the four major GlyR subunits (a13 and b) at 6, 24 h and 3, 7 and 10 days after SCI in adult male rats. SCI was induced at the T9 level by transection. Results: Our results show a complicated temporal and spatial pattern of alteration in GlyR mRNA expression levels after SCI. Temporal and spatial variations with different degrees and direction (up or downregulation) of expression alteration were observed. The greatest variation was seen in GlyRa1, whereas GlyRa2 was downregulated in all regions following SCI. Conclusion: This study shows that alteration in GlyR expression starts as early as 6 h after SCI. The most significant points of this research are temporal elevation of GlyRa1 and continuous reduction of GlyRa2. Alterations in GlyR expression within the spinal cord may have a key role in the development of pathological pain. Therefore, control of GlyR expression could represent a novel therapeutic avenue for the development of new painkiller agents in SCI.

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The Vesicular GABA Transporter, VGAT, Localizes to Synaptic Vesicles in Sets of Glycinergic as Well as GABAergic Neurons

Cited by 563 publications

References 75 publications

Differential Expression of GABA and Glutamate‐receptor Subunits and Enzymes Involved in GABA Metabolism between Electrophysiologically Identified Hippocampal CA1 Pyramidal Cells and Interneurons

Differential Expression of GABA and Glutamate‐receptor Subunits and Enzymes Involved in GABA Metabolism between Electrophysiologically Identified Hippocampal CA1 Pyramidal Cells and Interneurons

Extrasynaptic localization of GABA in the developing mouse cerebellum

Differential expression of glycine receptor subunit messenger RNA in the rat following spinal cord injury

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