Hyper-excitability of corticothalamic PT neurons in mPFC promotes irritability in the mouse model of Alzheimer's disease.
Cell Rep
; 41(5): 111577, 2022 11 01.
Article
em En
| MEDLINE
| ID: mdl-36323265
ABSTRACT
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.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Doença de Alzheimer
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article