Building models for postmortem abnormalities in hippocampus of schizophrenics.
Postmortem studies have suggested that there is abnormal GABAergic activity in the hippocampus in schizophrenia (SZ). In micro-dissected human hippocampal slices, a loss of interneurons and a compensatory upregulation of GABAA receptor binding activity on interneurons, but not PNs, has suggested that disinhibitory GABA-to-GABA connections are abnormal in stratum oriens (SO) of CA3/2, but not CA1, in schizophrenia. Abnormal expression changes in the expression of kainate receptor (KAR) subunits 5, 6 and 7, as well as an inwardly-rectifying hyperpolarization-activated cationic channel (Ih3; HCN3) may play important roles in regulating GABA cell activity at the SO CA3/2 locus. The exclusive neurons at this site are GABAergic interneurons; these cells also receive direct projections from the basolateral amygdala (BLA). When the BLA is stimulated by stereotaxic infusion of picrotoxin in rats, KARs influence axodendritic and presynaptic inhibitory mechanisms that regulate both inhibitory and disinhibitory interneurons in the SO-CA3/2 locus. The rat model described here was specifically developed to extend our understanding of these and other postmortem findings and has suggested that GABAergic abnormalities and possible disturbances in oscillatory rhythms may be related to a dysfunction of disinhibitory interneurons at the SO-CA3/2 site of schizophrenics.
Program in Structural and Molecular Neuroscience and Harvard Brain Tissue Resource Center, McLean Hospital, Belmont, MA, USA; Department of Psychiatry and Program in Neuroscience, Harvard Medical School, Boston, MA, USA. Electronic address: fbenes@mclean.harvard.edu.
Francine M
FM
Benes
D000200:Action Potentials / Q000502:physiology; D000818:Animals; D004195:Disease Models, Animal; D006624:Hippocampus / Q000473:pathology*; D006801:Humans; D007395:Interneurons / Q000473:pathology* / Q000502:physiology; D008959:Models, Neurological; D009434:Neural Pathways / Q000473:pathology; D011180:Postmortem Changes; D051381:Rats; D012559:Schizophrenia / Q000473:pathology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D005680:gamma-Aminobutyric Acid
Axoaxonic; Disinhibitory interneurons; Fast-spiking interneurons; GRIK1; GRIK2; GRIK3; GluR5; GluR6; GluR7; HCN3; Presynaptic inhibition; Rhythmic oscillations