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Theses Doctoral

Optical characterization of dopamine release in the globus pallidus and striatum

Meszaros, Jozsef

The measurement of dopamine neurotransmission in the brain has evolved alongside techniques for measuring neuronal activity. This evolution has progressed from coarse physical inspection (using lesions or dialysis approaches) to measuring electrical signatures of the phenomena of interest. Most recently, an optical revolution has taken hold within the neurosciences. We present an optical dopamine measurement technique as a companion to burgeoning neural activity monitors such as GCaMP. The electrical consequences of individual glutamate molecules impinging upon a postsynaptic membrane can be captured in an electrophysiological trace. On the other hand, dopamine has no consistent, measureable postsynaptic effects and therefore cannot easily be measured electrophysiologically. Researchers have instead used the electrochemical features of dopamine to measure samples of it in physical space. This approach, termed cyclic voltammetry, has generated nearly all of the existing knowledge about the precise characteristics of dopamine release. While a reliable method for measuring dopamine release from heavily innervated areas, cyclic voltammetry lacks the resolving power to establish release from dopamine terminals in other areas of interest. One such area is the external globus pallidus (GPe), the focus of this work. Research performed nearly thirty years prior to this thesis established the presence of sparsely distributed dopamine varicosities within the GPe. Here, we leverage FFN102, a newly developed optical method used as a proxy for dopamine release, to measure dopamine release in this area. Based on previous literature showing that dopamine varicosities were present in the GPe and that dopamine receptors exist on principal cells in the area, we hypothesized that these dopamine varicosities were capable of releasing FFN102. Moreover, previous work had shown that anatomically, the most prominent dopaminergic innervation to the GPe came from the substantia nigra. By validating the FFN102 method in the GPe, we showed that a substance is released which likely reflects dopamine vesicle release. Moreover, the use of two dopamine depletion mouse models allowed us to conclude that FFN102 is released exclusively from dopamine terminals. Finally, we advanced the understanding of dopamine release in the area by examining whether pharmacological manipulation could alter the amount of FFN102 released from dopamine terminals.

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More About This Work

Academic Units
Neurobiology and Behavior
Thesis Advisors
Sulzer, David
Kellendonk, Christoph B.
Degree
Ph.D., Columbia University
Published Here
October 26, 2017
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