Inhibition of subicular seizure-labeled c-fos+ neurons alleviates cognitive deficit in epilepsy
10.3867/j.issn.1000-3002.2023.07.005
- Author:
Lin YANG
1
;
Qi ZHANG
;
Xueqing WU
;
Xiaoyun QIU
;
Fan FEI
;
Nanxi LAI
;
Yuyi ZHENG
;
Mengdi ZHANG
;
Qingyang ZHANG
;
Yu WANG
;
Fei WANG
;
Cenglin XU
;
Yeping RUAN
;
Yi WANG
;
Zhong CHEN
Author Information
1. Key Laboratory of Neuropharmacology and Translation-al Medicine of Zhejiang Province,School of Pharmaceutical Sciences,Zhejiang Chinese Medical Univer-sity,Hangzhou 310053,China
- Keywords:
epilepsy;
cognitive deficit;
subiculum;
seizure-tagged c-fos+ neurons
- From:
Chinese Journal of Pharmacology and Toxicology
2023;37(7):482-483
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE Cognitive deficit is a com-mon comorbidity in temporal lobe epilepsy(TLE)and that is not well controlled by current therapeutics.Currently,how epileptic seizure affects cognitive performance remains largely unclear.The subiculum is the major out-put of the hippocampus,which projects to entorhinal cor-tex and other more distinct brain regions.Physiologically,the subiculum codes spatial working memory and naviga-tion information including place,speed,and trajectory.Importantly,prior studies have noted the importance of the subiculum in the beginning,spreading,and generaliz-ing process of hippocampal seizure.How seizure-activated neurons in subiculum participate in cognitive impairment remains largely elusive.METHODS In this study,we sought to label the subicular seizure-activated c-fos+ neu-rons with a special promoter with enhanced synaptic activity-responsive element E-SARE in the subiculum,combined with chemogenetics and designer receptors exclusively activated by designer drugs(DREADDs),Ca2+ fiber photometry approaches,and behavioral tasks,to reveal the role of these neurons in cognitive impairment in epilepsy.RESULTS We found that chemogenetic inhibi-tion of subicular seizure-tagged c-fos+ neurons(mainly CaMK Ⅱ α+ glutamatergic neurons)alleviates seizure generalization and improves cognitive performance in the hippocampal CA3 kindling TLE model.While inhibition of seizure-labeled c-fos+ GABAergic interneuron shows no effect on seizure and cognition.As a comparison,che-mogenetic inhibition of the whole subicular CaMK Ⅱ α+ neuron impairs cognitive function in na?ve mice in basal condition.Notably,inhibition of subicular seizure-tagged c-fos+ neurons enhances the recruitment of cognition-responsive c-fos+ neurons via increasing neural excitability during cognition tasks.CONCLUSION Our results dem-onstrate that subicular seizure-activated c-fos+ neurons contribute to cognitive impairment in TLE,suggesting sei-zure-tagged c-fos+ neurons as the potential therapeutic target to alleviate cognitive impairment in TLE.
