UC San Diego

It has long been proposed that volitional, dexterous forelimb movements require rapid online correction to achieve consistent end-point accuracy. Sensory feedback from the limb provides one source of information about movement errors. However, some corrective movements occur too quickly to be explained purely by sensory feedback. Instead, it is thought that internal copies of motor commands are sent to the cerebellum to generate estimates that predict the state of the limb, providing a faster feedback pathway for movement correction. A potential source of internal copies comes from a subset of interneurons in the cervical spinal cord, propriospinal neurons (PNs), which send projections to the lateral reticular nucleus (LRN). PNs receive descending motor information and send bifurcating projections; one branch descends to innervate forelimb motor neurons, and the other branch ascends to the LRN. Thus, it is thought that PNs send internal copies to the LRN before they are sent to the cerebellum. Therefore, a putative neural candidate for receiving, processing, and sending internal copy information to the cerebellum is the LRN, a brainstem nucleus located in the ventral, caudal medulla. Ultimately, the LRN is hypothesized to be a hub for spinal internal copies and an access point to evaluate internal copy function. Chapter 1 provides a review of motor control principles that highlight the hypothesized function of internal copies for dexterous forelimb movement and motivates the use of the LRN to evaluate internal copy function. Chapter 2 provides evidence that the LRN is involved in executing accurate dexterous forelimb movements because mouse pellet reaching behavior is changed when LRN neurons are ablated or optogenetically silenced. Reach trajectories change (ablation) and slow down (optogenetic inhibition) to maintain their reaching accuracy, a classic compensation for ataxic limb movements. Chapter 3 describes an approach to recording single unit activity in the LRN of awake behaving animals. Our results indicate, LRN neurons are heterogeneously modulated during active forelimb movement. Beyond control of forelimb movement, determining the functional significance of internal copies will provide insight into strategies the nervous system uses to continuously monitor and rapidly update different motor and cognitive behaviors.