July 22, 2021 | 5 pm | Zoom
Striatal determinants of network pathophysiology in Parkinson’s and Huntington’s diseases.
The striatum is a key component of the basal ganglia circuitry controlling goal-directed action and habit. The principal striatal neurons are GABAergic, spiny projection neuron (SPNs). SPNs can be sub-divided into two classes based upon their network connectivity and expression of G-protein coupled receptors (GPCRs) that transduce neuromodulatory signaling by dopamine and acetylcholine. These GPCRs control both moment-to-moment excitability of SPNs, as well as long-term synaptic plasticity, which is thought to underlie reward-based learning. In Parkinson’s disease (PD) and Huntington’s disease (HD), the mechanisms controlling these determinants of SPN activity are disrupted in complementary ways, leading to the hypokinetic and hyperkinetic symptoms, respectively. In the seminar, our current understanding of how striatal function is altered in PD and HD will be discussed, with an emphasis on factors governing synaptic plasticity.