title: Regulation of synaptic plasticity in a schizophrenia model.
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.
authors.affiliation: Program in Structural and Molecular Neuroscience, McLean Hospital, Belmont, MA 02478, USA.
authors.forename: Barbara
authors.initials: B
authors.lastname: Gisabella
authors.forename: Vadim Y
authors.initials: VY
authors.lastname: Bolshakov
authors.forename: Francine M
authors.initials: FM
authors.lastname: Benes
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004594:Electrophysiology; D006624:Hippocampus / Q000503:physiopathology*; D008297:Male; D009473:Neuronal Plasticity; D051381:Rats; D017207:Rats, Sprague-Dawley; D043643:Receptor, Muscarinic M1 / Q000378:metabolism; D043587:Receptor, Muscarinic M3 / Q000378:metabolism; D011950:Receptors, Cholinergic / Q000378:metabolism; D012559:Schizophrenia / Q000473:pathology* / Q000503:physiopathology; D005680:gamma-Aminobutyric Acid / Q000502:physiology
chemical_list: D043643:Receptor, Muscarinic M1; D043587:Receptor, Muscarinic M3; D011950:Receptors, Cholinergic; D005680:gamma-Aminobutyric Acid