Date of Award

1-1-2020

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 (v, 44 pages) : color illustrations.

Dissertation/Thesis Chair

Annalisa Scimemi

Committee Members

Joanna L Workman, Damian Zuloaga

Keywords

Dopamine, EAAC1, Reward, Striatum, Glutamic acid, Neurotransmitters, GABA, Basal ganglia, Reward (Psychology), Learning

Abstract

The basal ganglia are a collection of subcortical nuclei responsible for action selection. The striatum is the primary input of the basal ganglia and forms two distinct feedback loops with the motor cortex. Within the striatum, projection neurons receive cortical inputs via glutamatergic synapses, and modulation via cholinergic synapses and dopaminergic projections. These projection neurons create two separate pathways to the principal output of the basal ganglia, the substantia nigra pars reticulata. The striatum uses these two pathways to filter cortical motor inputs and integrate those inputs with dopaminergic motor and reward inputs to determine action selection output. The GABAergic striatal projection neurons are distinguished based on whether they express D1-receptors or D2-receptors. Previous work has been conducted indicating that the loss of the neuronal glutamate transporter, EAAC1, expressed within the striatum by the projection neurons, results in a variety of behavioral changes including compulsion-like stereotyped grooming behaviors. What remains unknown is how EAAC1 impacts differences in reward-motivated voluntary motor actions. Herein, we seek to answer this question using behavioral approaches, and discover a novel phenotype previously undescribed in EAAC1 / mice. These mice show an impulsive behavioral phenotype in which they are faster than WT mice to initiate a reward-motivated behavior action sequence. This lays the groundwork for future research on how EAAC1 affects the overall function of the striatum and basal ganglia in determining action selection on the molecular level. This also suggests evidence, for the first time, of a tangible effect of spillover due to the supposed role of EAAC1 at glutamatergic synapses.

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