Regulation of synaptic plasticity in a schizophrenia model

doi:10.1073/pnas.0506034102

Regulation of synaptic plasticity in a schizophrenia model

^*Program in Structural and Molecular Neuroscience, McLean Hospital, Belmont, MA 02478; and ^‡Program in Neuroscience and ^†Department of Psychiatry, Harvard Medical School, Boston, MA 02115

Communicated by Erminio Costa, University of Illinois, Chicago, IL, July 16, 2005 (received for review May 19, 2005)

Abstract

The pathology of schizophrenia is characterized by increased hippocampal activity at baseline and during auditory hallucinations. Animal-model studies in which the flow of activity to the hippocampus is increased through decreased amygdalar GABAergic inhibition have shown alterations of hippocampal circuitry similar to schizophrenia, but the functional importance of this phenomenon remains unclear. We provide evidence of decreased hippocampal feed-forward and tonic GABA-mediated inhibition in this animal model, complementing increased hippocampal activity seen in neuroimaging and postmortem studies. We demonstrate that GABA dysfunction increases long-term potentiation through activation of the cholinergic system, offering a new mechanism for pharmacological strategies of this disorder.

Footnotes

↵ § To whom correspondence should be addressed at: McLean Hospital, 115 Mill Street, Belmont, MA 02478. E-mail: fbenes{at}mclean.harvard.edu.
Author contributions: B.G. and F.M.B. designed research; B.G. performed research; V.Y.B. contributed new reagents/analytic tools; B.G. and V.Y.B. analyzed data; B.G. and F.M.B. wrote the paper; and V.Y.B. provided expert guidance.
Abbreviations: BLA, basolateral amygdala; EPSP, excitatory postsynaptic potential; fEPSP, field EPSP; IPSCs, inhibitory postsynaptic currents; LTP, long-term potentiation; PICRO, picrotoxin; SAL, saline; sIPSCs, spontaneous IPSCs; SZ, schizophrenia.