title: Kainate receptor-mediated modulation of hippocampal fast spiking interneurons in a rat model of schizophrenia.
abstract: Kainate receptor (KAR) subunits are believed to be involved in abnormal GABAergic neurotransmission in the hippocampus (HIPP) in schizophrenia (SZ) and bipolar disorder. Postmortem studies have shown changes in the expression of the GluR5/6 subunits of KARs in the stratum oriens (SO) of sectors CA2/3, where the basolateral amygdala (BLA) sends a robust projection. Previous work using a rat model of SZ demonstrated that BLA activation leads to electrophysiological changes in fast-spiking interneurons in SO of CA2/3. The present study explores KAR modulation of interneurons in CA2/3 in response to BLA activation. Intrinsic firing properties of these interneurons through KAR-mediated activity were measured with patch-clamp recordings from rats that received 15 days of picrotoxin infusion into the BLA. Chronic BLA activation induced changes in the firing properties of CA2/3 interneurons associated with modifications in the function of KARs. Specifically, the responsiveness of these interneurons to activation of KARs was diminished in picrotoxin-treated rats, while the after-hyperpolarization (AHP) amplitude was increased. In addition, we tested blockers of KAR subunits which have been shown to have altered gene expression in SO sector CA2/3 of SZ subjects. The GluR5 antagonist UBP296 further decreased AP frequency and increased AHP amplitude in picrotoxin-treated rats. Application of the GluR6/7 antagonist NS102 suggested that activation of GluR6/7 KARs may be required to maintain the high firing rates in SO interneurons in the presence of KA. Moreover, the GluR6/7 KAR-mediated signaling may be suppressed in PICRO-treated rats. Our findings indicate that glutamatergic activity from the BLA may modulate the firing properties of CA2/3 interneurons through GluR5 and GluR6/7 KARs. These receptors are expressed in GABAergic interneurons and play a key role in the synchronization of gamma oscillations. Modulation of interneuronal activity through KARs in response to amygdala activation may lead to abnormal oscillatory rhythms reported in SZ subjects.
authors.affiliation: Program in Structural and Molecular Neuroscience, McLean Hospital, Belmont, Massachusetts, United States of America.
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: D000679:Amygdala / Q000378:metabolism; D000818:Animals; D001714:Bipolar Disorder / Q000378:metabolism / Q000473:pathology; D001931:Brain Mapping / Q000379:methods; D056651:CA2 Region, Hippocampal / Q000378:metabolism; D004195:Disease Models, Animal; D004594:Electrophysiology / Q000379:methods; D006624:Hippocampus / Q000378:metabolism*; D007395:Interneurons / Q000378:metabolism*; D007608:Kainic Acid / Q000494:pharmacology; D008297:Male; D009991:Oscillometry / Q000379:methods; D018408:Patch-Clamp Techniques; D010852:Picrotoxin / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018092:Kainic Acid Receptors / Q000378:metabolism*; D012559:Schizophrenia / Q000378:metabolism* / Q000473:pathology; D015398:Signal Transduction
chemical_list: D007608:Kainic Acid; D010852:Picrotoxin; D018092:Kainic Acid Receptors