The deep cerebellar nuclei (DCN) represent output channels of the cerebellum, and they transmit integrated sensorimotor signals to modulate limb movements. But the functional relevance of identifiable neuronal subpopulations within the DCN remains unclear. Here, we examine a genetically tractable population of neurons in the mouse interposed anterior nucleus (IntA). We show that these neurons represent a subset of glutamatergic neurons in the IntA and constitute a specific element of an internal feedback circuit within the cerebellar cortex and cerebello-thalamo-cortical pathway associated with limb control. Ablation and optogenetic stimulation of these neurons disrupt efficacy of skilled reach and locomotor movement and reveal that they control positioning and timing of the forelimb and hindlimb. Together, our findings uncover the function of a distinct neuronal subpopulation in the deep cerebellum and delineate the anatomical substrates and kinematic parameters through which it modulates precision of discrete and rhythmic limb movements.

Although its dense connections with other brain areas suggests that the claustrum is involved in higher-order brain functions, little is known about the properties of claustrum neurons. Using whole-cell patch clamp recordings in acute brain slices of mice, we characterized the intrinsic electrical properties of more than 300 claustral neurons and used unsupervised clustering of these properties to define distinct cell types. Differences in intrinsic properties permitted separation of interneurons (INs) from projection neurons (PNs). Five subtypes of PNs could be further identified by differences in their adaptation of action potential (AP) frequency and amplitude, as well as their AP firing variability. Injection of retrogradely transported fluorescent beads revealed that PN subtypes differed in their projection targets: one projected solely to subcortical areas while three out of the remaining four targeted cortical areas. INs expressing parvalbumin (PV), somatostatin (SST), or vasoactive intestinal peptide (VIP) formed a heterogenous group. PV-INs were readily distinguishable from VIP-INs and SST-INs, while the latter two were clustered together. To distinguish IN subtypes, an artificial neural network was trained to distinguish the properties of PV-INs, SST-INs, and VIP-INs, as independently identified through their expression of marker proteins. A user-friendly, machine-learning tool that uses intrinsic electrical properties to distinguish these eight different types of claustral cells was developed to facilitate implementation of our classification scheme. Systematic classification of claustrum neurons lays the foundation for future determinations of claustrum circuit function, which will advance our understanding of the role of the claustrum in brain function.

The claustrum is a thin sheet of neurons that is densely connected to many cortical regions and has been implicated in numerous high-order brain functions. Such brain functions arise from brain states that are influenced by neuromodulatory pathways from the cholinergic basal forebrain, dopaminergic substantia nigra and ventral tegmental area, and serotonergic raphe. Recent revelations that the claustrum receives dense input from these structures have inspired investigation of state-dependent control of the claustrum. Here, we review neuromodulation in the claustrum—from anatomical connectivity to behavioral manipulations—to inform future analyses of claustral function.