2455 - Stereotypy of intracortical and cortex-body interactions due to MECP2 disruption and imbalance of excitation and inhibition
Rett syndrome (RTT) is a devastating neurodevelopmental disorder, caused by disruptions to the MECP2 gene, and resulting in severe cognitive and motor impairment. Previous work strongly suggests that healthy MECP2 function is required to have a normal balance between excitatory and inhibitory neurons. However, the details of how neural circuit dynamics and motor function are disrupted remain unclear. How might imbalanced E/I cause problems for motor function in RTT? We address this question in the motor cortex of awake, freely behaving rats, comparing normal rats with a rat model of RTT. We record single-unit neuronal activity with multi-electrode arrays in the deep layer motor cortex. Simultaneously, we record the three-dimensional body movement of the rats. Firstly, we found that MECP2 knockout rats tend to have excessive synchrony among neurons in the motor cortex, which results in a low-dimensional neural motor code. More specifically, we find that synchrony is anticorrelated with the diversity of relationships among neurons and anticorrelated with the diversity of relationships between neurons and body movements. To further test how our observations are related to an E/I imbalance, we pharmacologically altered inhibitory synaptic interactions in normal rats. We were able to recapitulate many of the phenomena we found in MECP2 deficient rats by enhancing inhibition in normal rats. Our results suggest that RTT-related E/I imbalance in the motor cortex gives rise to excessive synchrony and, consequently, excessive stereotypy of the neural motor code. Such stereotyped brain-body relationships may underlie the abnormal motor function in RTT.