Optogenetic inhibition of ventral hippocampal neurons alleviates associative motor learning dysfunction in a rodent model of schizophrenia

Autoři: Zheng-li Fan aff001;  Bing Wu aff001;  Guang-yan Wu aff001;  Juan Yao aff001;  Xuan Li aff001;  Ke-hui Hu aff003;  Zhen-hua Zhou aff004;  Jian-feng Sui aff001
Působiště autorů: Department of Physiology, College of Basic Medical Science, Army Medical University, Chongqing, P.R. China aff001;  Experimental Center of Basic Medicine, College of Basic Medical Science, Army Medical University, Chongqing, P.R. China aff002;  Department of Rehabilitation, Suining Central Hospital, Suining, P.R. China aff003;  Department of Neurology, First Affiliated Hospital of Army Medical University, Chongqing, P.R. China aff004
Vyšlo v časopise: PLoS ONE 14(12)
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.pone.0227200


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.

Klíčová slova:

Cognitive impairment – Electromyography – Fiber optics – Hippocampus – Neurons – Optogenetics – Rats – Deep-brain stimulation


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