Failure to Communicate: Early Alterations in Synaptic Function Precede Cell Death in Huntington’s Disease

The human brain is estimated to contain about 100 billion neurons that form an estimated 100 trillion synaptic connections. With such a complex organ, where do we begin when searching for a cure for a particular disease of the brain? In this presentation, I will discuss Huntington’s disease (HD), a devastating neurodegenerative disorder that has a single, known genetic cause. The predictable genetics of HD has allowed researchers to accurately model the disease in a laboratory setting. This has greatly accelerated our basic understanding of the neurobiology underlying cell death in disease and has identified numerous therapeutic strategies and targets for the treatment of HD. A general introduction to HD will be provided, followed by the presentation of electrophysiological and live-imaging approaches that demonstrate an impairment in synaptic communication in HD brain tissue. Interestingly, the deficits in synaptic function appear prior to cell death, suggesting that targeting the early synaptic dysfunction in HD may slow or prevent the onset of disease symptoms. Additional strategies to cure HD will also be discussed, including a brief description of an exciting, new clinical trial.