Date of Award
Bachelor of Science
Medium spiny neurons (MSNs) make up more than 95% of the cells in the striatum and therefore represent the main structures for specific information processing in the striatum. MSNs can be separated into two sub-populations based on the type of dopamine receptor they express and their target region. Roughly one-half of all MSNs express D1 dopamine receptors and send information to the substantia nigra pars compacta (SNc) and are called D1-MSNs. D1-MSNs are responsible for promoting movement execution. The other sub-population of MSNs expresses D2 dopamine receptors and for this reason, they are called D2-MSNs. D2-MSNs send information to the external capsule of the globus pallidus and suppress the execution of competing actions. Previously, our lab has shown that mice that lack the neuronal glutamate transporter EAAC1, hypo-functional in patients with obsessive-compulsive disorder (OCD), repeatedly performed stereotyped activities. In principle, this result could be explained by hyperactivity of D1-MSNs or by reduced D2-MSN activation. Since both populations of MSNs receive powerful GABAergic inputs from striatal neurons, we aimed to identify specific deficits in GABAergic inhibition onto D1- and D2-MSNs. By using slice electrophysiology and optogenetics, we show that D1-MSNs receive weaker GABAergic inputs in the absence of EAAC1, indicating that EAAC1 limits GABAergic inhibition onto D1-MSNs, not D2-MSNs. These findings suggest that one of the mechanisms by which EAAC1 might contribute to motor hyperactivity in OCD is by altering the coordinated recruitment of D1- and D2-MSNs.
Affinnih, Nurat, "Optical Activation of GABA Release from D2-Medium Spiny Neurons" (2020). Biological Sciences. 77.