in-vivo-wireless-optogenetic-control-of-skilled-motor-behavior

<em>In Vivo</em> Wireless Optogenetic Control of Skilled Motor Behavior

Fine motor skills are essential in everyday life and can be compromised in several nervous system disorders. The acquisition and performance of these ...

Stanford University

Skilled motor behavior requires bihemispheric coordination, and participation of striatal outputs originating from two neuronal groups identified by distinctive expression of D1 or D2 dopamine receptors. We trained mice to reach for and grasp a single food pellet and determined how the output pathways differently affected forelimb trajectory and task efficiency. We found that inhibition and excitation of D1-expressing spiny projection neurons (D1SPNs) have a similar effect on kinematics results, as if excitation and inhibition disrupt the whole ensemble dynamics and not exclusively one kind of output. In contrast, D2SPNs participate in control of target accuracy. Further, ex vivo electrophysiological comparison of naive mice and mice exposed to the task showed stronger striatal neuronal connectivity for ipsilateral D1 and contralateral D2 neurons in relation to the paw used. In summary, while the output pathways work together to smoothly execute skill movements, practice of the movement itself changes synaptic patterns.

Striatal bilateral control of skilled forelimb movement.

Dendritic spine dynamics are thought to be substrates for motor learning and memory, and altered spine dynamics often lead to impaired performance. Here, we describe an exception to this rule by studying mice lacking paired immunoglobulin receptor B (PirB). Pyramidal neuron dendrites in PirB mice have increased spine formation rates and density. Surprisingly, PirB mice learn a skilled reaching task faster than wild-type (WT) littermates. Furthermore, stabilization of learning-induced spines is elevated in PirB mice. Mechanistically, single-spine uncaging experiments suggest that PirB is required for NMDA receptor (NMDAR)-dependent spine shrinkage. The degree of survival of newly formed spines correlates with performance, suggesting that increased spine stability is advantageous for learning. Acute inhibition of PirB function in M1 of adult WT mice increases the survival of learning-induced spines and enhances motor learning. These results demonstrate that there are limits on motor learning that can be lifted by manipulating PirB, even in adulthood.

Article	Year
Striatal bilateral control of skilled forelimb movement. Cell reports\| PubMed ID: 33472081	2021
Enhancing motor learning by increasing the stability of newly formed dendritic spines in the motor cortex. Neuron\| PubMed ID: 34437845	2021

Omar Jaidar

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