Dopamine Regulates Motor Learning through Astrocytes in Primary Motor Cortex

still rudimentary.Recent research has unveiled important roles of astrocytes in brain functions that werepreviously underestimated. They are now recognized as active participants in variouscritical processes in the brain, including neural plasticity. In our preliminary studies, weexplored the calcium dynamics of astrocytes in the primary motor cortex, a key area formotor control and learning, and revealed a potential role of astrocytic calcium activity inmotor learning. This astrocytic activity is closely correlated with neuronal firing, and isresponsive to dopamine release originating from the midbrain ventral tegmental area(VTA). In this proposal, we hypothesize that astrocytes play a crucial role in processingaction and outcome of motor action critical for motor learning, which depends ondopaminergic input from VTA.We aim to further our preliminary findings to fully explore the roles of dopamine onastrocytes in motor learning. Specifically, during the learning process, we will 1) elucidatethe essential features of astrocytic calcium activity critical for motor learning, 2)characterize dopamine release dynamics in M1 during the process, 3) elaborate therelationship between dopamine signaling and astrocytic calcium activity, and finally 4)establish the causal relationship of astrocytic dopamine signaling with motor learningand neuronal signaling. To achieve these objectives, new generation of highly sensitivedopamine sensor, simultaneous two-photon imaging and astrocyte-specific dopaminereceptor knockdown techniques are employed to generate real-time and high spatialresolution imaging results in behaving animals necessary for proving the hypothesis.By studying astrocytes and their role in motor learning, we can unlock new pathways formedical and technological advancements that benefit society at different levels. Thisresearch holds the promise of transforming how we understand and enhance motorfunctions, leading to significant improvements in health and human performance in thelong term.