Synaptic proteins in the hippocampus indicative of increased neuronal activity in CA3 in schizophrenia

Wei Li, Subroto Ghose, Kelly Gleason, Anita Begovic, Jessica Perez, John Bartko, Scott Russo, Anthony D. Wagner, Lynn Selemon, Carol A. Tamminga

Research output: Contribution to journalArticle

35 Scopus citations

Abstract

Objective: In schizophrenia, hippocampal perfusion is increased and declarativememory function is degraded. Based on an a priori model of hippocampal dysfunction in schizophrenic psychosis, the authors postulated molecular and cellular changes in CA3 consistent with increased NMDA receptor signaling. Method: Postmortem hippocampal subfield tissue (CA3, CA1) from subjects with schizophrenia and nonpsychiatric comparison subjects was analyzed using Western blotting and Golgi histochemistry to examine the hypothesized outcomes. Results: The GluN2B-containing NMDA receptors (GluN2B/ GluN1) and their associated postsynaptic membrane protein PSD95 were both increased in schizophrenia in CA3 tissue, but not in CA1 tissue. Quantitative analyses of Golgi-stained hippocampal neurons showed an increase in spine density on CA3 pyramidal cell apical dendrites (stratum radiatum) and an increase in the number of thorny excrescences. Conclusions: The hippocampal data are consistent with increased excitatory signaling in CA3 and/orwith an elevation in silent synapses in CA3, a state that may contribute to an increase in long-term potentiation in CA3 with subsequent stimulation and "unsilencing." These changes are plausibly associated with increased associational activity in CA3, with degraded declarative memory function, and with formation of false memories with psychotic content. The influence of these hyperactive hippocampal projections on targets in the limbic neocortex could contribute to components of schizophrenia manifestations in other cerebral regions.

Original languageEnglish (US)
Pages (from-to)373-382
Number of pages10
JournalAmerican Journal of Psychiatry
Volume172
Issue number4
DOIs
StatePublished - Apr 1 2015

ASJC Scopus subject areas

  • Psychiatry and Mental health

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