| 论文题目: | Hyper-excitability of Corticothalamic PT Neurons in mPFC Promotes Irritability in the Mouse Model of Alzheimer's Disease |
| 作者: | Zhongyu Zhang, Ying Zhang, Ting Yuwen, Jiaxin Huo, Enyu Zheng, Wen Zhang, Jiali Li |
| 联系作者: | jialili@bjmu.edu.cn |
| 发表年度: | 2022 |
| DOI: | doi: 10.1016/j.celrep.2022.111577 |
| 摘要: | Neuropsychiatric symptoms in patients with Alzheimer's disease (AD) are presented as early as the mild cognitive 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 |
| 刊物名称: | Cell Reports |
| 论文出处: | https://www.sciencedirect.com/science/article/pii/S2211124722014383?via%3Dihub |
| 影响因子: | 9.995(2021IF) |
