Paradoxical effects of posterior intralaminar thalamic calretinin neurons on hippocampal seizure via distinct downstream circuits
Yingbei Qi,
Heming Cheng,
Qiuwen Lou,
Xia Wang,
Nanxi Lai,
Chenshu Gao,
Shuangshuang Wu,
Cenglin Xu,
Yeping Ruan,
Zhong Chen,
Yi Wang
Affiliations
Yingbei Qi
Institute of Pharmacology and Toxicology, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China
Heming Cheng
Key Laboratory of Neuropharmacology and Translational Medicine of Zhejiang Province, School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, China
Qiuwen Lou
Key Laboratory of Neuropharmacology and Translational Medicine of Zhejiang Province, School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, China
Xia Wang
Institute of Pharmacology and Toxicology, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China
Nanxi Lai
Institute of Pharmacology and Toxicology, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China
Chenshu Gao
Key Laboratory of Neuropharmacology and Translational Medicine of Zhejiang Province, School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, China
Shuangshuang Wu
Key Laboratory of Neuropharmacology and Translational Medicine of Zhejiang Province, School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, China
Cenglin Xu
Key Laboratory of Neuropharmacology and Translational Medicine of Zhejiang Province, School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, China
Yeping Ruan
Key Laboratory of Neuropharmacology and Translational Medicine of Zhejiang Province, School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, China
Zhong Chen
Institute of Pharmacology and Toxicology, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China; Key Laboratory of Neuropharmacology and Translational Medicine of Zhejiang Province, School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, China; Epilepsy Center, Department of Neurology, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China; Corresponding author
Yi Wang
Institute of Pharmacology and Toxicology, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China; Key Laboratory of Neuropharmacology and Translational Medicine of Zhejiang Province, School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, China; Epilepsy Center, Department of Neurology, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China; Corresponding author
Summary: Epilepsy is a circuit-level brain disorder characterized by hyperexcitatory seizures with unclear mechanisms. Here, we investigated the causal roles of calretinin (CR) neurons in the posterior intralaminar thalamic nucleus (PIL) in hippocampal seizures. Using c-fos mapping and calcium fiber photometry, we found that PIL CR neurons were activated during hippocampal seizures in a kindling model. Optogenetic activation of PIL CR neurons accelerated seizure development, whereas inhibition retarded seizure development. Further, viral-based circuit tracing verified that PIL CR neurons were long-range glutamatergic neurons, projecting toward various downstream regions. Interestingly, selective inhibition of PIL-lateral amygdala CR circuit attenuated seizure progression, whereas inhibition of PIL-zona incerta CR circuit presented an opposite effect. These results indicated that CR neurons in the PIL play separate roles in hippocampal seizures via distinct downstream circuits, which complements the pathogenic mechanisms of epilepsy and provides new insight for the precise medicine of epilepsy.
