title: Synaptic proteins in the hippocampus indicative of increased neuronal activity in CA3 in schizophrenia.
abstract: OBJECTIVE
  In schizophrenia, hippocampal perfusion is increased and declarative memory 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.
  
  
  METHODS
  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/or with 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.
authors.affiliation: From the Division of Translational Neuroscience in Schizophrenia, Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas; the Department of Neurobiology, Yale University School of Medicine, New Haven, Conn.; the Department of Psychology and Neuroscience Program, Stanford University, Palo Alto, Calif.; and the Department of Neuroscience, Mount Sinai Medical School, New York.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.forename: Subroto
authors.initials: S
authors.lastname: Ghose
authors.forename: Kelly
authors.initials: K
authors.lastname: Gleason
authors.forename: Anita
authors.initials: A
authors.lastname: Begovic
authors.forename: Jessica
authors.initials: J
authors.lastname: Perez
authors.forename: John
authors.initials: J
authors.lastname: Bartko
authors.forename: Scott
authors.initials: S
authors.lastname: Russo
authors.forename: Anthony D
authors.initials: AD
authors.lastname: Wagner
authors.forename: Lynn
authors.initials: L
authors.lastname: Selemon
authors.forename: Carol A
authors.initials: CA
authors.lastname: Tamminga
mesh_terms: D000328:Adult; D000368:Aged; D056547:CA1 Region, Hippocampal / Q000378:metabolism* / Q000473:pathology; D056654:CA3 Region, Hippocampal / Q000378:metabolism* / Q000473:pathology; D016022:Case-Control Studies; D049229:Dendritic Spines / Q000473:pathology; D000076122:Disks Large Homolog 4 Protein; D005260:Female; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D008875:Middle Aged; D017966:Pyramidal Cells / Q000473:pathology; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D012559:Schizophrenia / Q000378:metabolism* / Q000473:pathology
chemical_list: C501444:DLG4 protein, human; D000076122:Disks Large Homolog 4 Protein; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C121001:NR2B NMDA receptor; D016194:Receptors, N-Methyl-D-Aspartate