This project addresses these questions using TMS of the olfactory bulb in a mouse model of fentanyl self-administration paired with olfactory cues. The hypothesis is that TMS of the olfactory bulb induces plasticity changes in downstream circuits involved in learning and reward such as the piriform cortex and olfactory tubercle (part of the ventral striatum), and therefore can be used to reverse drug-induced plasticity in those areas and inhibit relapse to drug seeking induced by olfactory cues.
The first aim will determine the extent of activation by TMS of the olfactory bulb on the bulb itself, downstream targets, and contiguous areas using confocal imaging of c-fos immunohistochemistry.
The second aim will define the effects of different TMS parameters on downstream plasticity using brain slice electrophysiology combined with optogenetics.
The third aim will develop and validate a novel mouse model of fentanyl vapor self-administration and olfactory-cue-induced relapse that is compatible with the TMS model. The last and fourth aim will study the effects of olfactory bulb TMS on fentanyl-induced plasticity in the olfactory tubercle and olfactory-cue-induced relapse to fentanyl seeking.
|Yau, Hau-Jie; Wang, Dong V; Tsou, Jen-Hui et al. (2016) Pontomesencephalic Tegmental Afferents to VTA Non-dopamine Neurons Are Necessary for Appetitive Pavlovian Learning. Cell Rep 16:2699-2710|