Date of Award

1-1-2018

Language

English

Document Type

Master's Thesis

Degree Name

Master of Science (MS)

College/School/Department

Department of Biological Sciences

Content Description

1 online resource (ii, ix, 96 pages) : illustrations (some color)

Dissertation/Thesis Chair

Annalisa Scimemi

Committee Members

Gregory A Lnenicka, Damian Zuloaga

Keywords

EAAC1, Glutamate, Striatum, Glutamic acid, Neurotransmitters, Corpus striatum, Basal ganglia, Neurophysiology, Anxiety, Dopamine

Subject Categories

Biology | Neuroscience and Neurobiology

Abstract

The basal ganglia are subcortical nuclei that control the execution of learnt motor behaviors and emotions. The striatum, the main output nucleus of the basal ganglia, receives glutamatergic inputs from the cortex and thalamus and sends GABAergic inputs to the sub-thalamic nucleus via the axonal projections of D1- and D2-receptor (D1R and D2R) expressing medium spiny neurons (D1- and D2-MSNs, respectively). The dorsolateral striatum (DLS) is mainly involved in movement execution, whereas the ventromedial striatum (VMS) regulates emotions. Excitatory inputs onto D1- and D2-MSNs are mediated by post-synaptic ionotropic (GluA, GluN) and metabotropic glutamate receptors (mGluRI). The diffusion distance of glutamate from its release sites, is important to regulate the time course of excitatory transmission and depends on the local expression of glutamate transporters. Although the vast majority of glutamate transporters are localized in astrocytes, neuronal glutamate transporters are the closest to active release sites. In the hippocampus, the neuronal glutamate transporter EAAC1, limits glutamate spillover and inter-synaptic cross-talk. The Excitatory Amino Acid Carrier 1 (EAAC1) is localized in the peri-synaptic environment of excitatory synapses in striatal MSNs. In humans, non-functional polymorphisms in the gene encoding EAAC1 are associated with Obsessive Compulsive Disorder (OCD). What remains unknown are the molecular mechanisms by which EAAC1 regulates excitatory synaptic transmission onto striatal MSNs.

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