NMDA receptor antagonists like ketamine or phencyclidine (PCP) induce robust schizophrenia-like symptoms in rodents via glutamatergic disinhibition of cortico-limbo-thalamic substrates. We show that acute administration of PCP in the mouse elicits aberrant fronto-hippocampal and thalamo-cortical functional connectivity, an effect that can be prevented by pharmacological activation of M1/M4 muscarinic receptors. These changes highlight a previously unreported permissive contribution of muscarinic receptors on the aberrant connectional signatures produced by NMDAr antagonism which bear relevance for human connectivity mapping in hyperglutamatergic states and schizophrenia.
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