Cerebellospinal Neurons Regulate Motor Performance and Motor Learning.

To understand the neural basis of behavior, it is important to reveal how movements are planned, executed, and refined by networks of neurons distributed throughout the nervous system. Here, we report the neuroanatomical organization and behavioral roles of cerebellospinal (CeS) neurons. Using intersectional genetic techniques, we find that CeS neurons constitute a small minority of excitatory neurons in the fastigial and interpositus deep cerebellar nuclei, target pre-motor circuits in the ventral spinal cord and the brain, and control distinct aspects of movement. CeS neurons that project to the ipsilateral cervical cord are required for skilled forelimb performance, while CeS neurons that project to the contralateral cervical cord are involved in skilled locomotor learning. Together, this work establishes CeS neurons as a critical component of the neural circuitry for skilled movements and provides insights into the organizational logic of motor networks.

Decoding Cell Type Diversity Within the Spinal Cord.

To understand fundamental mechanisms of mammalian spinal cord function, it is necessary to reveal the diverse array of constituent spinal "cell types" - populations that can be consistently identified because they share a unique and cohesive set of characteristics. Many parameters can contribute to the definition of a spinal cord cell type, including location, morphology, lineage, electrophysiological properties, circuit features, gene expression patterns, and behavioral contribution. While it is not necessary for all of these features to align completely at all times to identify an individual cell type, a correlation of these characteristics paints a rich portrait of cell identity. This review will summarize recent advances in the identification of mammalian spinal cord neuronal cell types and will highlight the power of transcriptional profiling to identify and characterize the cell types of the spinal cord.

Massively Parallel Single Nucleus Transcriptional Profiling Defines Spinal Cord Neurons and Their Activity during Behavior.

To understand the cellular basis of behavior, it is necessary to know the cell types that exist in the nervous system and their contributions to function. Spinal networks are essential for sensory processing and motor behavior and provide a powerful system for identifying the cellular correlates of behavior. Here, we used massively parallel single nucleus RNA sequencing (snRNA-seq) to create an atlas of the adult mouse lumbar spinal cord. We identified and molecularly characterized 43 neuronal populations. Next, we leveraged the snRNA-seq approach to provide unbiased identification of neuronal populations that were active following a sensory and a motor behavior, using a transcriptional signature of neuronal activity. This approach can be used in the future to link single nucleus gene expression data with dynamic biological responses to behavior, injury, and disease.