NIH Research Festival
Dorsal striatum (DS) medial spiny neurons(MSN) of direct pathway (expressing D1 receptor, D1-MSN) and indirect pathway (expressing D2 receptor, D2-MSN) are involved in motor skill learning, however, the underlying neural mechanism remains largely unknown. To address this question, motor skill learning on accelerating rotarod was employed in this study. The rotarod accelerated from 4-40 rotations per min over 300 s, mice were trained with 10 trials per day on every other day for 8 training days. Each trial ended when the mouse failed to run on the rotarod or reached the maximum performance of 300 s. There was a 300-s resting between trials. A typical learning curve was that the latency on rotarod increased fast on day 1, and steadily reached a plateau over the following days. Bilateral partial ablation of DS D1-MSN or D2-MSN differently affected the motor skill learning: partial ablation of D1-MSN, resulting in D2-MSN-dominant DS, slowed down the learning; however, partial ablation of D2-MSN, resulting in D1-MSN-dominant DS, speeded up the learning. To further decode the neural mechanism of DS MSN underlying motor skill learning, we developed a custom miniature fluorescent microscope (miniScope) to concurrently record calcium activities of hundreds of striatal neurons longitudinally from mice training on accelerating rotarod. We identified two subpopulations of speed-related MSN: speed-depressing neurons(SDN) whose activities decreased as running speed increased, and speed-potentiating neurons(SPN) whose activities increased as running speed increased. We found that SDNs, not SPNs were related to the motor skill learning. The SDN number increased fast on day 1 and slowly reached a plateau over the following days, similar to the behavior learning curve, while the SPN number didn’t change over learning. Moreover, SDN activities, instead of SPN activities presented increased trial-to-trial correlation, which suggested increased trial-to-trial similarity and reduced trial-to-trial variability of SDN activities towards the end of learning. Moreover, over learning, D1 SDN number increased more significantly than D2 SDN, which suggested D1-MSN presented more contribution to this motor skill learning. Further, optogenetic silencing of SDNs significantly affected the learning curve: silencing of D1 SDN slowed down the learning curve, while silencing of D2 SDN speeded up the learning curve. Altogether, our results proposed that SDN encoded the learning and D1-MSN presented more contribution to the motor skill learning in DS.
Scientific Focus Area: Neuroscience
This page was last updated on Friday, March 26, 2021