Amygdala-dependent regulation of electrical properties of hippocampal interneurons in a model of schizophrenia.
BACKGROUND
Schizophrenia (SZ) involves dysfunction of gamma-aminobutyric acid (GABA)ergic transmission in the hippocampus (HIPP), particularly in sector CA2/3. Previous work using a rodent model of postmortem abnormalities in SZ demonstrated that activation of the basolateral amygdala (BLA) results in decreases of GABA currents in pyramidal neurons of CA2/3 but not CA1. In addition, a decrease of GABA cells has been reported in postmortem studies of the HIPP in SZ. In the present work we tested the hypothesis that BLA activation in this rodent model of SZ leads to changes in the electrical properties of interneurons located in sector CA2/3.


METHODS
Patch clamp recordings in HIPP slices were performed in rat HIPP slices after 15 days of infusion of picrotoxin into the BLA. The intrinsic and firing properties and hyperpolarization-activated currents (Ih) of interneurons were measured in stratum oriens (SO) of CA2/3 and CA1.


RESULTS
The BLA activation was associated with a lower resting membrane potential and an increased action potential firing rate in interneurons of CA2/3 but not CA1. Recordings from interneurons further demonstrated an increase of currents associated with hyperpolarization-activated cationic channels (Ih), which help to control neuronal firing rates and oscillatory rhythms.


CONCLUSIONS
Taken together, these results suggest that the enhanced BLA activity is capable of increasing the excitability of interneurons in SO of CA2/3 and might contribute to GABAergic dysfunction in SZ.
Gisabella
Barbara
B
Department of Psychiatry, Harvard Medical School, Boston, Massachusetts 02478, USA.
Cunningham
Miles G
MG
Bolshakov
Vadim Y
VY
Benes
Francine M
FM
D000200:Action Potentials; D000679:Amygdala / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D004195:Disease Models, Animal; D055724:Electrophysiological Phenomena; D018756:GABA Antagonists; D058787:GABA-A Receptor Antagonists; D006624:Hippocampus / Q000166:cytology / Q000503:physiopathology*; D066298:In Vitro Techniques; D007395:Interneurons / Q000502:physiology*; D008297:Male; D008564:Membrane Potentials; D009434:Neural Pathways; D010852:Picrotoxin; D017966:Pyramidal Cells / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012559:Schizophrenia / Q000503:physiopathology*
D018756:GABA Antagonists; D058787:GABA-A Receptor Antagonists; D010852:Picrotoxin