The brain's neurotransmitter system is of vital importance to the proper functioning of the brain. In particular, neurotransmitter dopamine has drawn considerable research interest in recent years due to its critical roles in neurological diseases and animal behaviors. This dissertation focuses on utilizing powerful electro-chemistry technique (fast-scan cyclic voltammetry, FSCV) to interrogate the neurotransmitter dynamics in live brain tissue. Both in vitro (brain slices) and in vivo electro-chemical studies of dopamine are presented in an optogenetics context. To achieve cell-type-specific control of dopamine activity, we used specifically tailored transgenic mice that conditionally express the opsin Channelrhodopsin-2 (ChR2) in only dopaminergic neurons. In brain slices of these transgenic animals, we systematically studied effective optogenetic induction of dopamine release at physiological levels. Real-time dopamine activity in response to temporally and spatially controlled optical stimulation was monitored by FSCV. We found that the temporal features and the level of dopamine release are non-linearly dependent on the light power, pulse width and the shape of the stimulation waveform. In addition, a novel chronically implantable two-way probe capable of both performing neuro-chemical sensing and delivering controlled optogenetic stimulation was developed. This probe was used for investigating the endogenous and light stimulation induced dopamine activity in live transgenic mice. More broadly, our framework combining electro-chemistry and optogenetic tools provides a powerful and practical approach to interrogate neurotransmitter dynamics in live brain tissue through cell-type-specific control of dopaminergic neurons.
Lu, Yao,
"Interrogating the neurotransmitter system with fast-scan cyclic voltammetry in an optogenetics context"
(2016).
Chemistry Theses and Dissertations.
Brown Digital Repository. Brown University Library.
https://doi.org/10.7301/Z0S46QB1
