The sense of movement (kinesthesia) provides an interoceptive internal readout of our physical actions in space
and is essential for our ability to move fluidly and effectively through our environment. Despite kinesthesia's
importance in motor function and self-reference, our understanding of this sense is plagued by glaring knowledge
gaps and inconsistencies. Movement sensations are traditionally believed to be a specialized function of type Ia
muscle spindle afferents. Yet, the apparent disconnect between the peripheral coding properties of this receptor
and the sensory stimuli known to evoke a sense of movement have raised questions regarding their primary role
in kinesthesia. Although proprioceptive interventions provide functional motor improvements for many conditions
such as stroke, Parkinson's disease, focal dystonia, peripheral neuropathies, and musculoskeletal injuries, the
lack of a clear scientific foundation for kinesthesia impacts our understanding of sensory-motor deficits and
prevents important breakthroughs from translating into clinical successes and targeted intervention strategies.
From our recent work we have multiple lines of evidence that suggest there may be sensory muscle receptors,
outside of the traditional muscle spindles and Golgi tendon organs that exhibit features consistent with a
kinesthetic sensor. First, our peripheral electrophysiological recordings in rat demonstrate a population of fast-
conducting rapidly-adapting afferents, that are distinct from muscle spindle and Golgi tendon organ afferents,
yet are selectively activated in the frequency bandwidth associated with kinesthetic illusions. Second, our
immunological analyses in mouse skeletal muscle reveal a new population of large caliber Calbindin28k+
afferents that do not associate with muscle spindle or Golgi tendon organ receptors but instead terminate in free
endings that spread out alongside extrafusal muscle fibers. In a movement-perception study with human neural-
machine interface amputees, we found that vibration-induce illusory kinesthetic percepts were linked to muscle
contraction not elongation. These results were corroborated in a human stroke model where we amplified
kinesthetic perception linked to active muscle contraction which resulted in improved reaching trajectories. With
these observations we hypothesize that there are candidate muscle sensory afferents, distinct from type Ia
afferents, which selectively respond to muscle fiber contraction.
The studies in this proposal will explore the relationships between the response properties and physical
characteristics of these candidate kinesthetic receptors and the traditionally defined muscle sensory receptors
using genetic, histological, and electrophysiological approaches. Additionally, we will examine this systems
functionality with respect to contractile features and its ability to serve as a stimulus for active movement sensing.
The discovery and evaluation of the cellular basis of kinesthesia will fundamentally transform our understanding
of sensory-motor control and, by extension, will impact design strategies for advanced neural-machine interface
prosthetic devices for amputees, as well as other disorders with sensory-motor deficiencies such as stroke.