Interactions between motor cortical forelimb regions and their influence on muscles reorganize across behaviors

Amy C. Kristl, Natalie Koh, Mark Agrios, Sajishnu Savya, Zhengyu Ma, Diya Basrai, Sarah Hsu and Andrew Miri ()
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Amy C. Kristl: Northwestern University, Department of Neurobiology
Natalie Koh: Northwestern University, Department of Neurobiology
Mark Agrios: Northwestern University, Department of Neurobiology
Sajishnu Savya: Northwestern University, Department of Neurobiology
Zhengyu Ma: Northwestern University, Department of Neurobiology
Diya Basrai: Northwestern University, Department of Neurobiology
Sarah Hsu: Northwestern University, Department of Neurobiology
Andrew Miri: Northwestern University, Department of Neurobiology

Nature Communications, 2025, vol. 16, issue 1, 1-16

Abstract: Abstract It remains unclear how classical models of motor cortical hierarchy align with emerging evidence of behavioral organization in motor cortex. To address this, we combined optogenetic inactivation, Neuropixels recording, and electromyography to quantify the pattern and influence of activity in the mouse analogs of forelimb premotor and primary motor cortex (RFA and CFA) during a single-forelimb reaching task and an ethologically-inspired, all-limb climbing behavior. Results revealed that RFA’s dominant influence on forelimb muscles and on CFA during reaching is replaced by a dominant influence of CFA on muscles and on RFA during climbing, even when forelimb muscle activity during climbing resembles that during reaching. Short-latency influence between regions on putative excitatory and inhibitory populations in different cortical laminae also showed behavioral specificity. Simultaneous recordings in both areas during climbing revealed a loss of activity timing differences seen during reaching previously interpreted as reflective of hierarchy. These findings demonstrate that hierarchical interactions between forelimb motor cortical regions vary between behavioral contexts.

Date: 2025
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DOI: 10.1038/s41467-025-65381-z

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