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Acute clozapine suppresses synchronized pyramidal synaptic network activity by increasing inhibition in the ferret prefrontal cortex
Journal article   Peer reviewed

Acute clozapine suppresses synchronized pyramidal synaptic network activity by increasing inhibition in the ferret prefrontal cortex

Wen-Jun Gao
Journal of neurophysiology, v 97(2), pp 1196-1208
Feb 2007
DOI: https://doi.org/10.1152/jn.00400.2006
PMID: 17182915

Abstract

Membrane Potentials - drug effects Dopamine Agonists - pharmacology Interneurons - physiology Synapses - drug effects Data Interpretation, Statistical Receptors, Dopamine D4 - agonists Interneurons - drug effects Nerve Net - drug effects Ferrets Prefrontal Cortex - cytology Excitatory Postsynaptic Potentials - drug effects Nerve Net - cytology Clozapine - pharmacology Animals Prefrontal Cortex - drug effects Pyramidal Cells - drug effects Antipsychotic Agents - pharmacology In Vitro Techniques Action Potentials - drug effects
Recent studies have indicated that impaired neural circuitry in the prefrontal cortex is a prominent feature of the neuropathology of schizophrenia. Clozapine is one of the most effective antipsychotic drugs used for this debilitating disease. Despite its effectiveness, the mechanism by which clozapine acts on prefrontal cortical circuitry remains poorly understood. In this study, in vitro multiple whole cell recordings were performed in slices of the ferret prefrontal cortex. Clozapine, which effectively inhibited the spontaneous synchronized network activities in the prefrontal neurons, achieved the suppressive effect by decreasing the recurrent excitation among pyramidal neurons and by enhancing the inhibitory inputs onto pyramidal cells through a likely network mechanism. Indeed, under the condition of disinhibition, the depressing effects were reversed and clozapine enhanced the recurrent excitation. These results suggest that the therapeutic actions of clozapine in alleviating the positive symptoms of schizophrenia are achieved, at least partially, through the readjustment of synaptic balance between the excitation and inhibition in the prefrontal cortical circuitry.

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