Abstract

Schizophrenia (SZ) is a serious and incurable mental disorder characterized by clinical manifestations of positive and negative symptoms and cognitive dysfunction. High-frequency deep brain stimulation (DBS) of the ventral hippocampus (VHP) has been recently applied as a therapeutic approach for SZ in both experimental and clinical studies. However, little is known about the precise mechanism of VHP-DBS treatment for SZ and the role of hippocampal cell activation in the pathogenesis of SZ. With optogenetic technology in this study, we tried to inhibit neuronal activity in the VHP which has dense projections to the prefrontal cortex, before measuring long stumulus-induced delay eyeblink conditioning (long-dEBC) in a rodent model of SZ. Rats were administrated with phencyclidine (PCP, 3 mg/kg, 1/d, ip) for successive 7 days before optogenetic intervention. The current data show that PCP administration causes significant impairment in the acquisition and timing of long-dEBC; the inhibition of bilateral VHP neurons alleviates the decreased acquisition and impaired timing of longd-dEBC in PCP-administered rats. The results provide direct evidence at the cellular level that the inhibition of VHP neuronal cells may be a prominent effect of hippocampal DBS intervention, and increased activity in the hippocampal network play a pivotal role in SZ.

Highlights

  • Schizophrenia (SZ) is a severe, chronic, refractory mental disorder characterized by functional derangements in multiple brain regions, such as hippocampus and prefrontal cortex (PFC)[1]

  • These results suggested that long-delay EBC (dEBC) behavior model could be successfully established in rats, and it would be impaired by PCP administration

  • The neuronal cell bodies, the afferent neural fibers originating in remote brain areas, or even local glial cells are all possible candidates of deep brain stimulation (DBS) targets

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Summary

Introduction

Schizophrenia (SZ) is a severe, chronic, refractory mental disorder characterized by functional derangements in multiple brain regions, such as hippocampus and prefrontal cortex (PFC)[1]. High-frequency deep brain stimulation (DBS) is an effective alternative therapy to treat patients with motor and mental dysfunctions such as Parkinson’s disease, depression, and obsessive-compulsive disorder[2,3,4,5,6]. Optogenetic inhibition of ventral hippocampal neurons alleviates associative motor learning dysfunction collection and analysis, decision to publish, or preparation of the manuscript

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