| Title | Hyper-excitability of corticothalamic PT neurons in mPFC promotes irritability in the mouse model of Alzheimer's disease |
| Authors | Zhang, Zhongyu Zhang, Ying Ting, Yuwen Huo, Jiaxin Zheng, Enyu Zhang, Wen Li, Jiali |
| Affiliation | Peking Univ, Natl Inst Drug Dependence, Beijing, Peoples R China Peking Univ, Hlth Sci Ctr, Sch Basic Med Sci, Dept Pharmacol, Beijing, Peoples R China Chinese Acad Sci, Kunming Inst Zool, Chinese Acad Sci & Yunnan Prov, Key Lab Anim Models & Human Dis Mech, Kunming, Yunnan, Peoples R China Peking Univ, McGovern Inst Brain Res, PKU, Beijing, Peoples R China Univ Chinese Acad Sci, Kunming Coll Life Sci, Kunming, Yunnan, Peoples R China Chinese Acad Sci, Kunming Inst Zool, Natl Resource Ctr Nonhuman Primates, Kunming Primate Res Ctr,Natl Res Facil Phenotyp &, Kunming, Peoples R China |
| Keywords | MILD COGNITIVE IMPAIRMENT MEDIAL PREFRONTAL CORTEX PYRAMIDAL NEURONS NEUROPSYCHIATRIC SYMPTOMS RECEPTOR MODULATION EMOTION STOICHIOMETRY AGGRESSION PREVALENCE SUBUNITS |
| Issue Date | 1-Nov-2022 |
| Publisher | CELL REPORTS |
| Abstract | Neuropsychiatric symptoms in patients with Alzheimer's disease (AD) are presented as early as the mild cogni-tive impairment (MCI) stage. However, it remains unclear whether separate neuronal populations encode distinct aspects of the neuropsychiatric symptoms and drive them differently. Here, we report that pyramidal tract (PT) neurons projecting to the thalamus, but not to the pons or medulla, in the medial prefrontal cortex (mPFC) of the mouse model of AD show increased excitability, which is associated with increased irritability and aggressivity. Decreased Kv6.3 in corticothalamic PT neurons contributes to hyper-excitability, which is tightly associated with aggressive behaviors. Overexpression of Kv6.3 not only prevents abnormal excitability of corticothalamic PT neurons in mPFC, but also rescues aggressive behaviors of 3xTg model mice. Our study provides causal evidence for the contribution of corticothalamic PT neurons to irritability in the 3xTg model of AD and reveals circuit mechanisms used by PT neurons to regulate neuropsychiatric symptoms in AD. |
| URI | http://hdl.handle.net/20.500.11897/659053 |
| ISSN | 2211-1247 |
| DOI | 10.1016/j.celrep.2022.111577 |
| Indexed | SCI(E) |
| Appears in Collections: | 医学部待认领 |
