Description:

Andrew Miller Postdoc, Lerner Lab, Dept. of Neuroscience

When we learn new motor skills, excitatory synapses in the dorsal striatum undergo changes in early and late learning phases, in some cases depending on dopamine (DA) release. The major excitatory inputs to the dorsal striatum are the motor cortex and intralaminar thalamus. 

Prominent models suggest that changes in striatal subregions the Dorso-Medial Striatum (DMS) and Dorso-Lateral Striatum (DLS) may underlie early and late learning, respectively, and that excitatory input from the cortex is crucial to early learning, while the relatively understudied contributions of the thalamo-striatal pathways may allow for maintenance of expert performance once cortex becomes dispensable. This project tests these models directly and asks: What specific molecular events in the striatum underlie the transition from naive to early motor learning to expert performance? As well as: How do cortex and thalamus cooperate to subserve motor learning in the striatum? Utilizing a combination of in vivo  fiber photometry and ex vivo slice physiology, I observe pre-synaptic changes to excitatory input engagement over the course or learning, as well as post-synaptic changes to particular synapses, which depend on the identity of the excitatory input and post-synaptic cell type. 

Among other insights, preliminary results hint at a form of thalamus-specific plasticity not shown by cortico-striatal projections, supporting previous literature suggesting that these inputs may follow separate plasticity rules. These data will enrich the interpretations of the previous experiments that were unable to experimentally separate cortico- vs. thalamo-striatal afferents and add mechanistic detail to our picture of how sub-regional differences in striatum subserve motor learning.