DISSOCIABLE ROLES FOR THE ANTERIOR LATERAL MOTOR CORTEX IN ACTION EXECUTION AND WORKING MEMORY

The premotor cortex integrates past experiences with future motor plans to guide flexible behavior. Within this network, the anterior lateral motor cortex (ALM) is critical for memory-guided directional licking in mice. ALM exhibits preparatory activity and drives contralateral movements when stimulated optogenetically. However, single-neuron recordings reveal that ~50% of ALM neurons preferentially encode contralateral licks and the remainder are tuned to ipsilateral movements, suggesting functionally distinct subpopulations. To causally dissociate ALM’s roles in action execution and working memory, we developed a novel, open-source, directional action-updating task requiring mice to integrate previous trial outcome and action direction to update future choices. With training, mice use previous trial outcome and direction of licking to update future actions. Expert mice adopt an optimal strategy to solve the task by dynamically repeating rewarded actions and changing unrewarded actions. Using temporally precise optogenetic inhibition, we found that silencing ALM at the go cue selectively disrupts contralateral action execution, in line with ALM’s role in motor output. In contrast, inhibiting ALM during high working-memory epochs biases animals toward contralateral choice on subsequent trials, suggesting that ALM maintains ipsilateral working-memory signals. Preliminary single-cell two-photon calcium imaging data suggest partially distinct neuronal clusters engaged during action execution and working memory epochs. Together, our data confirm​ a role for ALM neurons in contralateral action execution and a novel role in ipsilateral working memory. Distinct neural populations might govern motor output and working memory, enabling flexible history-dependent action selection.