Exploring Altered Cortical Activity Dynamics in Huntington’s Disease
Huntington’s disease (HD) is a fatal inherited neurodegenerative disorder caused by a single gene mutation. Most patients present with disordered cognition and movement in middle age due to striatal and cortical neuron degeneration. However underlying HD processes begin earlier and are incompletely understood. Although striatal projection neurons are most vulnerable, cortical pathology likely primarily drives cognitive dysfunction in HD and may impact striatum health via extensive cortical-striatal projections. Using voltage-sensitive dye imaging, we monitored the activity of cortical neurons in HD-model mice, where we found sensory-evoked signals spread more extensively. This suggests an excitation/inhibition imbalance, the details of which we are clarifying with additional experiments. Ultimately, the above could affect motor and cognitive performance in HD and contribute to neuronal toxicity mediated by excessive excitatory neurotransmission. This research furthers our understanding of early brain circuit changes in HD and how they contribute to neurodegeneration; hopefully these findings will inform future early HD treatment interventions. Results will also be published in scientific journals and communicated to the media.