Speaker: Giselle Fernandes (Sur Lab)

Title: The role of altered neuromodulation in motor dysfunction in Rett Syndrom

Abstract: Rett Syndrome is a severe neurodevelopmental disorder caused by mutations in the MeCP2 gene. One of the most devastating symptoms of Rett Syndrome is the disruption of motor function. Patients lose purposeful use of their hands and develop repetitive movements, rigidity, and dystonia. The primary motor cortex, crucial for movement and learning, is modulated by norepinephrine from the Locus Coeruleus (LC), where phasic activity enhances motor learning. While MeCP2 loss reduces global norepinephrine, its impact on LC activity and motor function remains unclear. Using a cued lever-press task, we found that MeCP2 deficiency in the LC impairs task-specific axonal activity and norepinephrine release, abolishing reinforcement signals and consequently delaying motor learning. In addition, wildtype mice developed a stereotypical trajectory of their motor movements (i.e. lever presses) across the training period, with a decrease in both the variability and jerk of their lever presses. However, LC-MeCP2-deficient mice failed to refine the accuracy and reproducibility of their lever movements. This indicates a role for LC-MeCP2 in both the accuracy of behavioral performance as well as the execution of goal-driven, reproducible motor movements. Finally, in vivo two-photon calcium imaging revealed disrupted population activity of neurons in the motor cortex, highlighting the role of LC-MeCP2 in motor control and its dysfunction in Rett Syndrome. These findings elucidate a role for the norepinephrine system in the development of motor control and extend our understanding of the neuromodulatory systems that underlie motor dysfunction in Rett Syndrome.

Speaker: Sabrina Drammis (TDS and Graybiel Lab)

Title: TBD

Abstract: TBD