Presentation Abstract

Program#/Poster#: 839.12/M19
Title: Nicotine-evoked recruitment of prefrontal, signal detection-mediating mechanisms, are attenuated in the neonatal ventral hippocampal lesion model of schizophrenia
Location: South Hall A
Presentation Time: Wednesday, Oct 21, 2009, 4:00 PM - 5:00 PM
Authors: *S. A. WESCOTT1, H. GRITTON1, V. PARIKH1, J. P. BRUNO2, M. SARTER1;
1Psychology and Neurosci. Program, Univ. of Michigan, Ann Arbor, MI; 2Psychology and Neurosci. Program, Ohio State Univ., Columbus, OH
Abstract: Deficits in attentional performance represent core symptoms of the cognitive impairments of schizophrenic patients. However, the neuronal mechanisms responsible for such impairments have remained largely unclear. We previously demonstrated that the detection of cues in attention-demanding contexts is mediated via transient increases in cholinergic neurotransmission in the medial prefrontal cortex (mPFC). Furthermore, the stimulation of nicotinic acetylcholine receptors (nAChRs) in the mPFC recruits the glutamatergic-cholinergic interactions that result in the generation of such transients and, in performing animals, amplifies cue-evoked transients. Neonatal lesions of the ventral hippocampus disrupt telencephalic-mesolimbic-basal forebrain communication and therefore have been considered a useful model for studying the neuronal mechanisms underlying the cognitive impairments of schizophrenia. We employed the electrochemical techniques and research approaches described in Parikh et al. (J. Neurosci., 2008) in order to assess the efficacy of the nicotine-evoked recruitment of the signal detection-mediating circuitry in the mPFC. Briefly, choline-sensitive microelectrodes were implanted into the mPFC, together with a glass capillary pipette for pressure-ejections of compounds. Cholinergic transients were measured using fixed potential amperometry. In addition to the test of the effects of nicotine (40 pmol - 4 nmol), we also assessed cholinergic transients following depolarization of the recording field by pressure ejections of KCl (70 nM; 70 nL). The main results indicate that in animals with neonatal ventral hippocampal lesions, nicotine failed to evoke cholinergic transients. The amplitudes of transients evoked by K+ were attenuated by about 50% when compared with those recorded in the mPFC of sham-lesioned controls. These results suggest that neonatal hippocampal lesions fundamentally disrupt the mPFC detection circuit. It seems unlikely that this effect is due to an attenuated capacity of cholinergic neurons to respond to stimulation; rather, local glutamatergic and/or dopaminergic mediators can no longer be recruited by nicotine in order to generate a cholinergic transient. Ongoing research seeks to determine the mechanisms responsible for this profound characteristic of this animal model, to specify the developmental nature of this effect, and to rescue, using pharmacological means, the ability of nicotine to recruit the detection circuit. This model appears useful for research designed to assess the efficacy of combined treatment with traditional antipsychotic compounds and putative cognition enhancers.
Disclosures:  S.A. Wescott, None; H. Gritton, None; V. Parikh, None; J.P. Bruno, None; M. Sarter, None.
Keyword(s): MEDIAL PREFRONTAL CORTEX
SCHIZOPHRENIA
ACETYLCHOLINE
Support: NIH Grant MH057436
NIH Grant MH080426
NIH Grant MH080332
[Authors]. [Abstract Title]. Program No. XXX.XX. 2009 Neuroscience Meeting Planner. Chicago, IL: Society for Neuroscience, 2009. Online.

2009 Copyright by the Society for Neuroscience all rights reserved. Permission to republish any abstract or part of any abstract in any form must be obtained in writing by SfN office prior to publication.




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