UC San Diego

Neuromodulators have been associated with learning but much of our knowledge comes from pharmacological and in vitro studies. Therefore, a mechanistic understanding of how these neuromodulators play a role on learning in vivo is lacking. We used motor learning as a robust learning platform previously established by our lab since the resulting structural and phenotypic changes are known in detail. Using this platform, we studied neuromodulators in high degrees of specificity in learning animals using both a loss and gain of function approach. Our loss of function approach consisted of a series of surgeries, viral injections, and CRISPR. However, with cutting-edge technology, came obstacles. Therefore, the loss of function approach served as a technical side of the project.

In contrast, the gain of function was the experimental side of the project. Our investigation began with neuromodulator acetylcholine, but hope to continue with all the neuromodulators. By using the tools of optogenetics, the acetylcholine system was upregulated in the motor cortex and the resulting behavioral effects were analyzed in mice learning a lever-press task. Since acetylcholine is involved in attention, I hypothesized that excess acetylcholine in the mouse motor cortex would accelerate motor learning. If my hypothesis is correct, then we can investigate exactly how acetylcholine controls plasticity during learning using in vivo two-photon calcium imaging. Successfully using various cutting-edge techniques and gaining a mechanistic understanding of how neuromodulators affect learning will expand our understanding of the brain and contribute to public health as better pharmacological approaches can be created to target these systems.