神经科学
基底神经节
帕金森病
锥体束
间接运动途径
生物
中脑
丘脑
帕金森病
运动皮层
中枢神经系统
医学
疾病
病理
刺激
作者
Liqiang Chen,Samuel Daniels,Rachel Dvorak,Hong-Yuan Chu
出处
期刊:Science Advances
[American Association for the Advancement of Science (AAAS)]
日期:2023-08-25
卷期号:9 (34)
标识
DOI:10.1126/sciadv.adg3038
摘要
Degeneration of midbrain dopaminergic (DA) neurons alters the connectivity and functionality of the basal ganglia-thalamocortical circuits in Parkinson’s disease (PD). Particularly, the aberrant outputs of the primary motor cortex (M1) contribute to parkinsonian motor deficits. However, cortical adaptations at cellular and synaptic levels in parkinsonism remain poorly understood. Using multidisciplinary approaches, we found that DA degeneration induces cell subtype– and input-specific reduction of thalamic excitation to M1 pyramidal tract (PT) neurons. At molecular level, we identified that N -methyl- d -aspartate (NMDA) receptors play a key role in mediating the reduced thalamocortical excitation to PT neurons. At circuit level, we showed that the reduced thalamocortical transmission in parkinsonian mice can be rescued by chemogenetically suppressing basal ganglia outputs. Together, our data suggest that cell subtype– and synapse-specific adaptations in M1 contribute to altered cortical outputs in parkinsonism and are important aspects of PD pathophysiology.
科研通智能强力驱动
Strongly Powered by AbleSci AI