title: A rodent model of schizophrenia derived from postmortem studies.
abstract: There is compelling postmortem evidence that GABA cell dysfunction plays a role in the pathophysiology of schizophrenia (SZ). Based on a unique distribution of postmortem abnormalities in layer II of the anterior cingulate cortex and sectors CA3/2 of the hippocampus, we postulated that afferent fibers from the basolateral amygdala to these sites may contribute to diminished GABAergic modulation in these disorders. To test this hypothesis, picrotoxin (PICRO), a non-competitive antagonist of the GABA-A receptor, is stereotaxically infused the basolateral complex of the amygdala (BLA) to increase the flow of excitatory activity into stratum oriens (SO) of sectors CA3/2 of the hippocampus. This pharmacological manipulation results in a selective reduction of GABAergic interneurons containing parvalbumin, calbindin and calretinin in CA3/2. Using single cell recordings in a hippocampal slide preparation, these changes in PICRO-treated rats seem to be associated with a reduction in evoked and spontaneous inhibitory post-synaptic potentials (sIPSCs) recorded from pyramidal neurons in sector CA3/2, but not CA1. A lower resting membrane potential and an increased action potential firing rate have been recorded in interneurons in the SO of CA2/3, but not CA1. Additionally, currents associated with hyperpolarization-activated cationic channels (Ih), which help to control neuronal firing rates of GABA cells in the hippocampus, were also increased. Overall, these studies support the view that postmortem studies contribute information for the development of empiric models of SZ, ones that can be used as translational tools for elucidating the functional changes that may be present in GABA cell subtypes their molecular regulatory mechanisms in this disorder.
authors.affiliation: Program in Structural and Molecular Neuroscience and Laboratory for Translational Neuroscience, McLean Hospital, Belmont, MA, United States.
authors.forename: Sabina
authors.initials: S
authors.lastname: Berretta
authors.forename: Barbara
authors.initials: B
authors.lastname: Gisabella
authors.forename: Francine M
authors.initials: FM
authors.lastname: Benes
mesh_terms: D000679:Amygdala / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D000818:Animals; D004195:Disease Models, Animal; D004594:Electrophysiology; D018756:GABA Antagonists / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D007150:Immunohistochemistry; D053444:Inhibitory Postsynaptic Potentials; D007395:Interneurons / Q000378:metabolism; D009434:Neural Pathways / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D009473:Neuronal Plasticity; D009474:Neurons / Q000378:metabolism; D010852:Picrotoxin / Q000494:pharmacology; D051381:Rats; D011963:Receptors, GABA-A / Q000378:metabolism; D012559:Schizophrenia / Q000378:metabolism / Q000503:physiopathology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D018756:GABA Antagonists; D010852:Picrotoxin; D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid