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While humans are known to have several premotor cortical areas, secondary motor cortex (M2) is often considered to be the only higher-order motor area of the mouse brain and is thought to combine properties of various human premotor cortices. Here, we show that axonal tracer, functional connectivity, myelin mapping, gene expression, and optogenetics data contradict this notion. Our analyses reveal three premotor areas in the mouse, anterior-lateral motor cortex (ALM), anterior-lateral M2 (aM2), and posterior-medial M2 (pM2), with distinct structural, functional, and behavioral properties. By using the same techniques across mice and humans, we show that ALM has strikingly similar functional and microstructural properties to human anterior ventral premotor areas and that aM2 and pM2 amalgamate properties of human pre-SMA and cingulate cortex. These results provide evidence for the existence of multiple premotor areas in the mouse and chart a comparative map between the motor systems of humans and mice. [Display omitted] • Combined multimodal data reveal multiple premotor areas within the mouse motor network • Three mouse premotor areas (ALM, aM2, pM2) have distinct structural and functional properties • ALM has striking similarity to human ventral premotor areas, such as PMv • aM2 and pM2 amalgamate properties of human pre-SMA and human cingulate cortex Lazari et al. provide evidence for the existence of multiple premotor areas within the mouse motor network. Three premotor areas, ALM, aM2, and pM2, have distinct structural, functional, and behavioral properties and show important similarities to and differences from the human motor system. [ABSTRACT FROM AUTHOR]

The basal ganglia (BG) are a group of subcortical nuclei responsible for motor and executive function. Central to BG function are striatal cells expressing D1 (D1R) and D2 (D2R) dopamine receptors. D1R and D2R cells are considered functional antagonists that facilitate voluntary movements and inhibit competing motor patterns, respectively. However, whether they maintain a uniform function across the striatum and what influence they exert outside the BG is unclear. Here, we address these questions by combining optogenetic activation of D1R and D2R cells in the mouse ventrolateral caudoputamen with fMRI. Striatal D1R/D2R stimulation evokes distinct activity within the BG-thalamocortical network and differentially engages cerebellar and prefrontal regions. Computational modeling of effective connectivity confirms that changes in D1R/D2R output drive functional relationships between these regions. Our results suggest a complex functional organization of striatal D1R/D2R cells and hint toward an interconnected fronto-BG-cerebellar network modulated by striatal D1R and D2R cells. [Display omitted] • Activity modulation of striatal D1R/D2R cells via optogenetics-fMRI • D1R/D2R cells recruit distinct areas in the basal ganglia-thalamocortical network • Striatal D1R/D2R cells differentially modulate prefrontal and cerebellar regions • Regression dynamic causal modeling reveals D1R/D2R output-driven relationships Grimm et al. report that cells located in the mouse ventrolateral striatum that express D1 (D1R) and D2 (D2R) dopamine receptors differentially recruit areas within the basal ganglia-thalamocortical network and differentially modulate prefrontal and cerebellar regions. [ABSTRACT FROM AUTHOR]