Forebrain and midbrain distribution of major benzodiazepine-sensitive GABAA receptor subunits in the adult C57 mouse as assessed with in situ hybridization

Abstract

In the adult brain, gamma-amino butyric acid (GABA) is the major inhibitory neurotransmitter. Understanding of the behavioral and pharmacological functions of GABA has been advanced by recent studies of mouse lines that possess mutations in various GABA receptor subtypes and associated proteins. Genetically altered mice have become important tools for discerning GABAergic function. Thus detailed knowledge of the anatomical distribution of different GABA A subtype receptors in mice is a prerequisite for understanding the neural circuitry underlying changes in normal and drug-induced behaviors seen in mutated mice. In the current study, we used in situ hybridization histochemistry with [35S]UTP-labeled riboprobes to examine the regional expression pattern of mRNA transcripts for 7 major GABA A receptor subunits in adjacent coronal brain sections (alpha 1, alpha 2, alpha 3, alpha 5, beta 2, beta 3, and gamma 2). Our results indicate that many of these GABAergic genes are co-expressed in much of the adult brain including the neocortex, hippocampus, amygdala, thalamus and striatum. However, each gene also shows a unique region-specific distribution pattern, indicative of distinct neuronal circuits that may serve specific physiological and pharmacological functions.

A Novel α5GABAAR-Positive Allosteric Modulator Reverses Hyperactivation of the Dopamine System in the MAM Model of Schizophrenia

“…The a5GABA A subunit shows a high affinity for GABA as well as a restricted pattern of expression, predominately in the HPC, with less expression in the cortex and thalamus (Heldt and Ressler, 2007;Ramos et al, 2004;Sur et al, 1999). In the adult HPC, a5GABA A R are located extrasynaptically, primarily in the dendritic fields of CA1, CA3, dentate gyrus, and subiculum (Sur et al, 1999).…”

“…The GABA A receptor is a pentameric anion-selective ion channel that is composed of different classes of subunits (a1-6, b1-3, g1-3, d, y, r, and e) (McKernan and Whiting, 1996). The a5GABA A receptor subunit is unique in its relatively confined distribution in the HPC, and to a lesser extent in the cortex and thalamus (Heldt and Ressler, 2007;Ramos et al, 2004;Serwanski et al, 2006). In addition, within CA1 and CA3 regions of the HPC, a5GABA A receptors are located extrasynaptically to pyramidal neurons (Fritschy and Mohler, 1995;Serwanski et al, 2006).…”

Regulation of the phosphoinositide‐3 kinase and mitogen‐activated protein kinase signaling pathways by progesterone and its reduced metabolites in the rat brain

“…THP is an allosteric agonist of GABA A receptors (Puia et al, 1990;Majewska, 1992;Follesa et al, 2001;Lambert et al, 2003;Belelli and Lambert, 2005;Belelli et al, 2006) and may increase the phosphorylation of ERK-1/2 and Akt in the hypothalamus and the phosphorylation of Akt in the hippocampus via membrane effects. Brain regional differences in the subunit composition of GABA A receptors (Heldt and Ressler, 2007), which are known to affect the response to THP (Belelli and Lambert, 2005;Belelli et al, 2006), may explain the regionally specific effects of THP on the MAPK and PI3K pathway. Unlike THP, progesterone and DHP bind to classical nuclear progesterone receptors (Rupprecht et al, 1993;Melcangi et al, 1999).…”

Cell-type specific deletion of GABA(A)α1 in corticotropin-releasing factor-containing neurons enhances anxiety and disrupts fear extinction

“…Fear training decreases GABA(A)α1 subunit containing neurons (19) and disruption of the GABA(A)α1 subunit receptor leads to enhanced synaptic plasticity in the lateral nucleus of the amygdala and enhanced auditory fear memory (20). GABA(A)α1 neurons can be found within the amygdala (21), BNST, and PVN (22), areas that also strongly express CRF. No studies to date have addressed the role of CRF containing GABA(A)α1 neurons in fear and anxiety disorders.…”