The primary motor cortex (M1) is an important site for learning new motor skills. While rewardis known to both enhance and accelerate motor learning, the mechanism by which reward exertsthese effects remains unclear. Previous studies in primates have demonstrated reward-relatedactivity in M1, however, it is not known whether reward is represented among different neuronalcell types in M1, or if the representations change over the course of reward-based associativelearning. We begin by reviewing advances in optogenetic methods that have enabled thedissection of cortical circuits underlying sensorimotor behaviours with a special focus on thefunctional roles of cell-type specific connections in governing sensorimotor informationprocessing and learning and memory. We then used in vivo, two-photon calcium imaging tocharacterize reward and reward-related responses in pyramidal neurons (PNs), PV-INs, SST-INsand VIP-INs while mice simultaneously performed a head-fixed auditory classical conditioningtask. We found that different cell types had distinct responses to the conditioned stimulus (CS)and to reward, and these responses underwent differential changes over the course of associativelearning. Notably, VIP-INs preferentially represented reward and their reward responsesincreased with learning, while PV-INs preferentially represented the CS, and their CS responsesincreased with learning. Lastly, to identify which brain regions might provide reward-relatedinput to VIP-INs, we performed cell-type specific monosynaptic rabies tracing and generatedcomparative brain-wide maps of input to VIP-INs, PV-INs, SST-INs and PNs in M1. Weidentified preferential input from the orbital frontal cortex (ORB) to VIP-INs compared to theother IN subtypes. These results suggest that ORB may convey reward-related input to VIP-INsand thereby disinhibit local MOP circuitry during reward-based learning. Together, these studiesprovide a potential mechanism for how reward modulates motor learning.
| Identifer | oai:union.ndltd.org:uottawa.ca/oai:ruor.uottawa.ca:10393/44366 |
| Date | 09 December 2022 |
| Creators | Lee, Candice |
| Contributors | Chen, Simon |
| Publisher | Université d'Ottawa / University of Ottawa |
| Source Sets | Université d’Ottawa |
| Language | English |
| Detected Language | English |
| Type | Thesis |
| Format | application/pdf |
| Rights | Attribution-NonCommercial-NoDerivatives 4.0 International, http://creativecommons.org/licenses/by-nc-nd/4.0/ |
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