Cognitive Deficits in Huntington’s Disease: Insights from Animal Models

Although Huntington’s disease (HD) is commonly recognized as a movement disorder, cognitive dysfunction is an intrinsic feature of the disease that often manifests before the onset of chorea. Neuronal loss has been demonstrated in anatomical regions known to be substrates of learning and memory, but cell loss is presaged by functional alterations. Changes in long-term synaptic plasticity, a substrate of memory processes, emerge in cognitive domains such as the hippocampus, the cortex, and the striatum. Insights from animal models provide mechanistic explanations of how long-term synaptic plasticity is altered in these regions. Glutamate and dopamine receptors play a crucial role in such changes and progress in this area of investigation has made significant strides in recent years. Based on these discoveries, novel therapies are being developed to improve clinical outcomes and ameliorate cognitive symptoms of HD.