The COMBO window: A chronic cranial implant for multiscale circuit interrogation in mice.

Neuroscientists studying the neural correlates of mouse behavior often lack access to the brain-wide activity patterns elicited during a specific task of interest. Fortunately, large-scale imaging is becoming increasingly accessible thanks to modalities such as Ca2+ imaging and functional ultrasound (fUS). However, these and other techniques often involve challenging cranial window procedures and are difficult to combine with other neuroscience tools. We address this need with an open-source 3D-printable cranial implant-the COMBO (ChrOnic Multimodal imaging and Behavioral Observation) window. The COMBO window enables chronic imaging of large portions of the brain in head-fixed mice while preserving orofacial movements. We validate the COMBO window stability using both brain-wide fUS and multisite two-photon imaging. Moreover, we demonstrate how the COMBO window facilitates the combination of optogenetics, fUS, and electrophysiology in the same animals to study the effects of circuit perturbations at both the brain-wide and single-neuron level. Overall, the COMBO window provides a versatile solution for performing multimodal brain recordings in head-fixed mice.

Brainstem neurons that command mammalian locomotor asymmetries.

Descending command neurons instruct spinal networks to execute basic locomotor functions, such as gait and speed. The command functions for gait and speed are symmetric, implying that a separate unknown system directs asymmetric movements, including the ability to move left or right. In the present study, we report that Chx10-lineage reticulospinal neurons act to control the direction of locomotor movements in mammals. Chx10 neurons exhibit mainly ipsilateral projection, and their selective unilateral activation causes ipsilateral turning movements in freely moving mice. Unilateral inhibition of Chx10 neurons causes contralateral turning movements. Paired left-right motor recordings identified distinct mechanisms for directional movements mediated via limb and axial spinal circuits. Finally, we identify sensorimotor brain regions that project on to Chx10 reticulospinal neurons, and demonstrate that their unilateral activation can impart left-right directional commands. Together these data identify the descending motor system that commands left-right locomotor asymmetries in mammals.