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, gamma-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 alpha3, and N-methyl-d-aspartate (NMDA)-receptor IIB mRNA, and presumed excitatory neurons expressed more GABA(A)-receptor alpha1, 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.
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, gamma-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 alpha3, and N-methyl-d-aspartate (NMDA)-receptor IIB mRNA, and presumed excitatory neurons expressed more GABA(A)-receptor alpha1, 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.
Authors: Jason E Davis; James H Eberwine; David A Hinkle; Paolo G Marciano; David F Meaney; Tracy K McIntosh Journal: Neurochem Res Date: 2004-06 Impact factor: 3.996
Authors: Mohsin Raza; Robert E Blair; Sompong Sombati; Dawn S Carter; Laxmikant S Deshpande; Robert J DeLorenzo Journal: Proc Natl Acad Sci U S A Date: 2004-12-06 Impact factor: 11.205
Authors: Xiangling Meng; Wei Wang; Hui Lu; Ling-Jie He; Wu Chen; Eugene S Chao; Marta L Fiorotto; Bin Tang; Jose A Herrera; Michelle L Seymour; Jeffrey L Neul; Fred A Pereira; Jianrong Tang; Mingshan Xue; Huda Y Zoghbi Journal: Elife Date: 2016-06-21 Impact factor: 8.140