Associative memory neurons are recruited in PFC-centered circuits to encode schizophrenia-like behavior by...

The severe stresses induce fear memory and mental disorders including anxiety, depression and schizophrenia. Their molecular and cellular mechanisms are expectedly revealed to develop therapeutic strategies. We aim to identify the stress-induced cellular units and neural circuits that are essential for fear memory and schizophrenia in cerebral cortices by behavior tasks, molecular biology, neural tracing and electrophysiology. The social stress by the resident/intruder paradigm leads to the fear memory specific to a resident CD1 mouse and schizophrenia-like behaviors as well as the synapse interconnections among medial prefrontal, auditory and S1Tr cortical neurons in intruder mice. This stress-induced synapse interconnection enables these cortical neurons be recruited as associative memory neurons that are featured by receiving the convergent synapse innervations from the interconnected areas and encoding the stressful signals including the battle sound and the pain signal from trunk-injury area generated in the social stress. The knockdown of dopaminergic receptor-II in the medial prefrontal cortex precludes the recruitment of associative memory neurons and the formation of fear memory and schizophrenia-like behaviors. Eticlopride as a dopaminergic receptor-II antagonist in the medial prefrontal cortex weakens the activities of associative memory neurons and relieves schizophrenia-like behavior. These associative memory neurons recruited by the social stress in the medial prefrontal, auditory and S1Tr cortices through dopaminergic receptors-II are essential for fear memory and schizophrenia.