Glutamate transporter control of excitation and inhibition in the striatum

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Animals have the ability to learn new motor skills and convert them into motor habits. The striatum, a major part of a key motor system in the brain called basal ganglia, is known to exert a fundamental role in controlling the execution of habitual actions. What is not known is exactly how the striatum coordinates the activity of its neurons to ensure proper execution of habitual actions. Recent findings suggest that a particular neurotransmitter transporter, the neuronal glutamate transporter EAAT3, might act as a key player in controlling the time course of excitatory transmission in multiple regions of the brain, including in the striatum. This research project will determine how EAAT3 controls glutamatergic signaling and synaptic integration onto two distinct types of striatal neurons. To accomplish this goal, the investigators use a comprehensive and multidisciplinary toolbox that includes electrophysiological, optical imaging, and computer modeling approaches, as well as mice genetically-engineered that express either D1- or D2-type dopamine neurons.. The project includes training of graduate and undergraduate students in Science, Technology, Engineering, and Mathematics (STEM) disciplines while advancing and transforming our knowledge of striatal circuits. Inclusion of underrepresented minorities and public engagement activities are an integral part of the project, to broaden its impact with the general public.Our ability to perform movements relies on the activity of a neuronal circuit known as the cortico-striatal-thalamo-cortical (CSTC) pathway. Relay of information in the CSTC pathway relies on the coordinated activation of neurons in the striatum, a major node of the CSTC pathway. The striatum is largely composed of two types of long-projection neurons that express either D1 or D2 dopamine receptors. Glutamate transporters are abundantly expressed in the striatum but their role in controlling the coordinated activity of striatal neurons remains enigmatic. The first goal of this project is to determine how neuronal glutamate transporters regulate excitatory transmission in D1- and D2-expressing neurons. The second goal is to determine how these transporters shape the temporal accuracy with which these cells relay information from incoming excitatory inputs. The experimental strategies entail innovative multi-disciplinary approaches based on electrophysiology, optogenetics, imaging and computer modeling. The proposed research will generate new knowledge on the functional role of glutamate transporters in the activity patterns and dynamics of circuits implicated in habitual movement execution.