Building models for postmortem abnormalities in hippocampus of schizophrenics

Area of Science:

• Neuroscience
• Psychiatry
• Cellular Biology

Background:

• Postmortem studies indicate abnormal GABAergic activity in the hippocampus of schizophrenia (SZ) patients.
• Human hippocampal slices show interneuron loss and GABAA receptor upregulation, suggesting abnormal disinhibitory GABA-to-GABA connections in SZ's CA3/2 stratum oriens (SO).

Purpose of the Study:

• To investigate the role of kainate receptors (KARs) and HCN3 channels in regulating GABAergic interneurons in the hippocampus.
• To extend understanding of postmortem findings in schizophrenia using a rat model.

Main Methods:

• Analysis of micro-dissected human hippocampal slices.
• Stimulation of the basolateral amygdala (BLA) via stereotaxic infusion of picrotoxin in a rat model.
• Investigation of KAR influence on inhibitory mechanisms in the SO-CA3/2 locus.

Main Results:

• Abnormal expression of KAR subunits (5, 6, 7) and HCN3 channels identified in the SO CA3/2 locus.
• KARs modulate axodendritic and presynaptic inhibition of interneurons in the SO-CA3/2 locus following BLA stimulation.

Conclusions:

• GABAergic abnormalities and potential disturbances in oscillatory rhythms in schizophrenia may stem from dysfunctional disinhibitory interneurons at the SO-CA3/2 site.
• The rat model provides insights into the mechanisms underlying hippocampal GABAergic dysfunction in schizophrenia.