Alteration of hyperpolarization-activated cation current-mediated metaplasticity contributes to electroconvulsive shock-induced learning and memory impairment in depressed rats

作者全名：Ren, Li; Yu, Jian; Chen, Hengsheng; Luo, Jie; Lv, Feng; Min, Su

作者地址：[Ren, Li; Luo, Jie; Lv, Feng; Min, Su] Chongqing Med Univ, Affiliated Hosp 1, Dept Anesthesiol, Chongqing, Peoples R China; [Yu, Jian] Tongji Univ, Shanghai Peoples Hosp 10, Anesthesia & Brain Res Inst, Dept Psychiat, Shanghai, Peoples R China; [Chen, Hengsheng] Minist Educ, China Int Sci & Technol Cooperat Base Child Dev &, Key Lab Child Dev & Disorders, Chongqing Key Lab Pediat, Chongqing, Peoples R China

通信作者：Lv, F; Min, S (通讯作者)，Chongqing Med Univ, Affiliated Hosp 1, Dept Anesthesiol, Chongqing, Peoples R China.

来源：FRONTIERS IN PSYCHIATRY

ESI学科分类：PSYCHIATRY/PSYCHOLOGY

WOS号：WOS:001252119700001

JCR分区：Q2

影响因子：3.2

年份：2024

卷号：15

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：electroconvulsive shock; depression; metaplasticity; excitability; hyperpolarization-activated cation current

摘要：Background Accompanied by a rapid and effective antidepressant effect, electroconvulsive shock (ECS) can also induce learning and memory impairment. Our previous research reported that metaplasticity is involved in this process. However, the mechanisms still remain unclear. This study investigated the role of I h current in the metaplastic changes and learning and memory impairment induced by ECS in depressive rats.Methods Depressive rats received ECS after modelling using chronic unpredictable. ZD7288, a type of I h current inhibitor was used to verify the effect of I h current. The sucrose preference test and Morris water maze were used for behavior testing. Changes in metaplasticity was assessed with the LTD/LTP threshold by stimulation at different frequencies. Spontaneous and evoked action potentials (APs) were measured to confirm difference of neuronal excitability. Additionally, the amplitude of I h current was analyzed.Results ECS exerts antidepressant effect, but also induce spatial learning and memory dysfunction. ECS up-regulates the LTD/LTP threshold. In rats treated with ECS, the frequency of spontaneous and evoked APs is significantly reduced. In addition, ECS induces changes in the intrinsic properties of AP, including a decrease of AP-half width and peak amplitude, and an increase in AP time to peak and post-hyperpolarization potential amplitude. In particular, ECS increases both instantaneous and steady-state I h currents. However, Inhibition of I h current with ZD7288 results in a relief of learning and memory impairment and a decrease in threshold, as well as a significant reversal of whole-cell electrophysiological changes.Conclusion ECS-induced learning and memory impairment is caused by neuronal hypoexcitability mediated metaplasticity, and upregulation of LTD/LTP threshold by an increase in I h current.

基金机构：National Natural Science Foundation of China10.13039/501100001809

基金资助正文：No Statement Available