Cerebral Cortex Advance Access originally published online on September 1, 2004
Cerebral Cortex 2005 15(5):663-669; doi:10.1093/cercor/bhh168
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Cerebral Cortex V 15 N 5 © Oxford University Press 2004; all rights reserved
Activation of Medial Prefrontal Cortex by Phencyclidine is Mediated via a Hippocampo-prefrontal Pathway
1 Department of Physiology, Fukushima Medical University School of Medicine, 1 Hikari-ga-oka, Fukushima 960-1295, Japan and 2 Department of Neuropsychiatry, Fukushima Medical University School of Medicine, 1 Hikari-ga-oka, Fukushima 960-1295, Japan
Address correspondence to Eiichi Jodo, Department of Physiology, Fukushima Medical University School of Medicine, 1 Hikari-ga-oka, Fukushima 960-1295, Japan. Email: jodo1019{at}fmu.ac.jp.
Phencyclidine (PCP) is a psychotomimetic drug that elicits schizophrenia-like symptoms in healthy persons, and administration of PCP to animals is used as a pharmacological model of schizophrenia. We recently demonstrated that systemic administration of PCP to rats produces long-lasting activation of medial prefrontal cortex (mPFC) neurons with augmentation of locomotor activity, whereas direct application of PCP to mPFC neurons has little effect on their firing activity. These findings suggest that PCP-induced activation of mPFC neurons is elicited mainly via excitatory inputs from regions outside the mPFC. In the present study, we examined effects of local application of PCP to the ventral hippocampus (vHIP) on firing activity of PFC neurons in freely moving rats. PCP locally perfused into the vHIP increased spontaneous discharges of PFC neurons during perfusion with augmentation of locomotor activity. Local application of a more selective NMDA receptor antagonist, MK801, to vHIP neurons under anesthesia increased the spontaneous firing rates of most neurons directly projecting to the mPFC, whereas local application of MK801 to mPFC neurons did not induce excitatory responses in any of those neurons. The present results indicate that tonic excitatory inputs from the vHIP to the PFC may trigger development of behavioral abnormalities.
Key Words: MK801 • NMDA receptor • PCP • prefrontal cortex • schizophrenia • ventral hippocampus
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