Date Approved

4-2019

Graduate Degree Type

Thesis

Degree Name

Health Sciences (M.H.S.)

Degree Program

Biomedical Sciences

First Advisor

Dr. Eric Ramsson

Second Advisor

Dr. Frank Sylvester

Third Advisor

Dr. Xiaojuan Xu

Academic Year

2018/2019

Abstract

The caudate putamen is a sub region of the basal ganglia, containing neural tracts important for cognition, reward learning, and voluntary motor function. Dopamine (DA) signaling received from the dopaminergic neurons of the substantia nigra pars compacta mediate locomotion, degradation of which is the characteristic neuropathology for Parkinson’s disease (PD). PD is an initially neurovegetative motor disorder but can progress to include cognitive impairments as well. Sundowner’s syndrome (SS) has been observed in patient populations with neurodegenerative diseases, characterized by the decline of cognition into evening hours. Due to the circadian influence which the hormone melatonin has on the sleep-wake cycle, attention has been drawn to its relationship with SS. While melatonin has been observed to decrease DA release, the real-time measurement of acute melatonin exposure on DA release within the caudate has yet to be studied. Utilizing various techniques of fast scan cyclic voltammetry (FSCV) in an ex vivo mouse model, we observed a decrease in DA release upon exposure to supraphysiological concentrations of melatonin. Results from this experiment support previous literature suggesting that activation of presynaptically expressed melatonin receptor 1 (MT1) plays an important physiological role in downregulating DA release. Additionally, results suggest that 1-hour of MT1 activation is a sufficient time-frame for significant downregulation of DA availability. This research seeks to deepen understanding of the complex roles melatonin has on neurotransmission.

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