Collapse of complexity of brain and body activity due to excessive inhibition and MeCP2 disruption

Abstract

Significance How does brain function falter when inhibition is not properly balanced by excitation in cerebral cortex? Here we show in rats that excessive inhibition leads to stereotyped, low-complexity relationships among neurons in motor cortex and body movements. We observed similar phenomena in rats with disrupted MeCP2 function, suggesting that imbalanced inhibition may contribute to motor dysfunction in Rett syndrome. Complex body movements require complex dynamics and coordination among neurons in motor cortex. Conversely, a long-standing theoretical notion supposes that if many neurons in motor cortex become excessively synchronized, they may lack the necessary complexity for healthy motor coding. However, direct experimental support for this idea is rare and underlying mechanisms are unclear. Here we recorded three-dimensional body movements and spiking activity of many single neurons in motor cortex of rats with enhanced synaptic inhibition and a transgenic rat model of Rett syndrome (RTT). For both cases, we found a collapse of complexity in the motor system. Reduced complexity was apparent in lower-dimensional, stereotyped brain–body interactions, neural synchrony, and simpler behavior. Our results demonstrate how imbalanced inhibition can cause excessive synchrony among movement-related neurons and, consequently, a stereotyped motor code. Excessive inhibition and synchrony may underlie abnormal motor function in RTT.