The central question that the Takeoka lab addresses is how animals learn to generate and control motor output in health and disease. Currently, the lab focuses on 1) understanding how sensory feedback, with a primary focus on proprioceptive and visual feedback, contribute to motor learning and recovery after traumatic injury and 2) study how motor memory is encoded within the spinal cord circuits.

Project 1. Motor learning and memory within the spinal cord: mechanisms of automaticity
 “It is like riding a bike.” This phrase refers to memory retention of a learned task without practice. It is clear from our everyday experience that the nervous system forms long-term motor memories. However, experimental demonstration of how motor memories are formed and retained remains elusive. Spinal circuits are at the heart of sensorimotor transformation to generate movements. Yet, it is challenging to disentangle how spinal circuits might contribute to motor skill acquisition and retention due to the physical continuum to the brain that also participates in those processes. As such, we know little about the identities of spinal neurons or circuits that underlie the bottom-up mechanisms of motor skill learning and retention. The term “muscle memory” is often used to describe the effortless execution of skilled motor patterns developed over time. The lab’s working model is the spinal cord network encodes the ability to execute complex motor patterns following repetitive training to form “spinal memory.” This project aims to dissect how repetitive motor training reinforces learned locomotor behavior, and influences neuronal recruitments and neuronal activity patterns of a specific population of spinal neurons. In this project, we plan to implement chronic recording and cell-type specific manipulation during spinal learning using ultra-flexible spinal probes. 

Project 2. Characterize mechanisms of memory consolidation by determining spinal activity sequences during rest. 
Leveraging in vivo spinal cord electrophysiology in behaving mice using flexible, high-density electrodes, our lab identified mechanisms in which spinal circuits, in the absence of brain input, learn to adapt motor outputs within minutes (Lavaud et al., BioRxiv). Using this simplified spinal learning paradigm, our data suggest the exciting possibility that mechanisms regulating spinal learning and memory recall are driven by specific cell types and circuits. Beyond distinct circuit requirements of naive and trained state, how do acute motor adjustments evolve into stable, optimal motor performance over time? Without additional practice, humans improve their motor performance through sleep or quiet wakefulness (offline learning). Our preliminary results using a simplified motor learning paradigm suggests that disruption of rest period with low frequency, low amplitude stimulation of the spinal cord indeed impedes spinal memory consolidation. We will use a skilled locomotor paradigm recently developed in our lab to unravel the circuit mechanisms of motor skill consolidation.

Project 3. Proprioceptive and visual feedback integration in forelimb reaching.
Using an intersectional mouse genetic model and lesion assays, we found that visual information processed via the superior colliculus, but not the primary visual cortex, is essential for goal-directed forelimb reaching and grasping functions. This project aims to identify how visual information via the superior colliculus is disseminated to motor output circuits and how proprioceptive information modulates the downstream output circuits. We will determine the projection-specific neuron activities (both optically identified single-unit and high-density recordings) and how neuronal SC activity and the brain are modulated by manipulating proprioceptive circuit activity. 

The Takeoka lab is looking for individuals with a strong drive to succeed, a positive attitude, and a background in either physiology or engineering with strong qualitative training. The candidate should also be a team player with good communication skills. In addition to scientific excellence and integrity, we value mentorship, collaboration, and innovation.