Parkinson's Disease is a neurodegenerative disorder primarily characterized by motor symptoms. In diagnosed Parkinson's patients, reduced coupling (i.e., decoupling) between the motor cortex and the striatum has been widely reported. However, the timing of its initial occurrence and its causal relationship with motor deficits remain unknown. Furthermore, the limited cell-type specificity of commonly used neuroimaging techniques for assessing brain function has hindered fundamental mechanistic studies.

Recently, the research team led by He Kai-Wen at the Interdisciplinary Research Center on Biology and Chemistry ( IRCBC), Shanghai Institute of Organic Chemistry (SIOC), Chinese Academy of Sciences, published a research paper titled "Behavior- and Cell Type-Specific Cortico-Striatal Decoupling in a Parkinson’s Disease-Like Mouse Model" in the journal Advanced Science. This work provides new insights into the decoupling and its underlying mechanisms in early-stage Parkinson's Disease.

The authors first established a methodology based on fiber photometry to assess coupling between the primary motor cortex (M1) and the striatum. They demonstrated that this method offers cell-type-specific resolution and can distinguish between coupling patterns associated with different behavioral paradigms (Fig. 1 I).

Subsequently, the team tracked changes in this cortico-striatal coupling in a chronic Parkinson's pathology mouse model (the α-Syn PFF model) (Fig. 1 II). They discovered a specific reduction in digging behavior-related coupling in the pathological mice, and notably, this decoupling occurred prior to the onset of the behavioral abnormalities themselves (Fig. 1 III).

Furthermore, through in vivo optogenetic manipulations (enhancing or disrupting) of the coupling between the motor cortex and striatum, the authors demonstrated a causal relationship between decoupling and abnormal digging behavior, identifying decoupling as a driver of the latter (Fig. 1 IV). Mechanistically, the study revealed that this decoupling is specifically mediated by striatal D1 medium spiny neurons (D1 MSNs) and is caused by dopamine deficiency (Fig. 1 V).

Fig. 1. Summary of the main findings.

The first author of the paper is Dr. Xu-Ran Yao, a recent Ph.D. graduate from the IRCBC, SIOC, CAS. Dr. Kai-Wen He is the sole corresponding author. Team members Yang Liu, Wei-Tong Zheng, and Mao-Qing Huang also made significant contributions. This work was supported by the National Natural Science Foundation of China, the Chinese Academy of Sciences, and the Shanghai Municipal Science and Technology Commission.

Link to the article: https://advanced.onlinelibrary.wiley.com/doi/10.1002/advs.202513670