Separating cognitive and motor processes in the behaving mouse.

The cognitive processes supporting complex animal behavior are closely associated with ubiquitous movements responsible for our posture, facial expressions, ability to actively sample our sensory environments, and other critical processes. These movements are strongly related to neural activity across much of the brain and are often highly correlated with ongoing cognitive processes, making it challenging to dissociate the neural dynamics that support cognitive processes from those supporting related movements. In such cases, a critical issue is whether cognitive processes are separable from related movements, or if they are driven by common neural mechanisms. Here, we demonstrate how the separability of cognitive and motor processes can be assessed, and, when separable, how the neural dynamics associated with each component can be isolated. We establish a novel two-context behavioral task in mice that involves multiple cognitive processes and show that commonly observed dynamics taken to support cognitive processes are strongly contaminated by movements. When cognitive and motor components are isolated using a novel approach for subspace decomposition, we find that they exhibit distinct dynamical trajectories. Further, properly accounting for movement revealed that largely separate populations of cells encode cognitive and motor variables, in contrast to the 'mixed selectivity' often reported. Accurately isolating the dynamics associated with particular cognitive and motor processes will be essential for developing conceptual and computational models of neural circuit function and evaluating the function of the cell types of which neural circuits are composed.

Molecular and anatomical organization of the dorsal raphe nucleus.

The dorsal raphe nucleus (DRN) is an important source of neuromodulators and has been implicated in a wide variety of behavioral and neurological disorders. The DRN is subdivided into distinct anatomical subregions comprised of multiple cell types, and its complex cellular organization has impeded efforts to investigate the distinct circuit and behavioral functions of its subdomains. Here we used single-cell RNA sequencing, in situ hybridization, anatomical tracing, and spatial correlation analysis to map the transcriptional and spatial profiles of cells from the mouse DRN. Our analysis of 39,411 single-cell transcriptomes revealed at least 18 distinct neuron subtypes and 5 serotonergic neuron subtypes with distinct molecular and anatomical properties, including a serotonergic neuron subtype that preferentially innervates the basal ganglia. Our study lays out the molecular organization of distinct serotonergic and non-serotonergic subsystems, and will facilitate the design of strategies for further dissection of the DRN and its diverse functions.