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Proc Natl Acad Sci U S A. 2008 Dec 30;105(52):20935-40. doi: 10.1073/pnas.0810153105. Epub 2008 Dec 22.

Circuitry-based gene expression profiles in GABA cells of the trisynaptic pathway in schizophrenics versus bipolars.

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  • 1Program in Structural and Molecular Neuroscience, McLean Hospital, Belmont, MA 02478, USA.


Significant reductions in GABAergic cell numbers and/or activity have been demonstrated in the hippocampus of subjects with schizophrenia and bipolar disorder. To understand how different subpopulations of interneurons are regulated, laser microdissection and gene expression profiling have been used to "deconstruct" the trisynaptic pathway, so that subtypes of GABA cells could be defined by their location in various layers of CA3/2 and CA1. The results suggest that the cellular endophenotypes for SZ and BD may be determined by multiple factors that include unique susceptibility genes for the respective disorders and altered integration among hippocampal GABA cells with extrinsic and intrinsic afferent fiber systems. The extensive and intricate data that has come from this study has provided insights into how a complex circuit, like the trisynaptic pathway, may be regulated in human hippocampus in both health and disease.

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