Publication Date

2018

Document Type

Dissertation

Committee Members

David Ladle, Ph.D. (Advisor); Mark Rich, M.D., Ph.D. (Committee Member); Katherine Excoffon, Ph.D. (Committee Member); Lynn Hartzler, Ph.D. (Committee Member); Patrick Sonner, Ph.D. (Committee Member)

Degree Name

Doctor of Philosophy (PhD)

Abstract

Proprioceptive circuits provide information regarding limb position and movement status, and are essential to producing correctly executed motor behaviors. Exploring the mechanisms underlying the formation of proprioceptive circuits is therefore critical for understanding neurological disorders with altered motor coordination and for restoring circuits damaged by injury. One important proprioceptive circuit, the stretch reflex circuit, is formed between proprioceptive sensory neurons (PSNs) and motor neurons (MNs) that innervate the same muscle. Progress has been made in understanding the spatial organization of MNs based on their muscle-specific subpopulation identities, which contributes to the specificity of stretch reflex circuit formation. However, whether PSNs share similar properties is underexplored. As PSNs form connections with MNs via highly elaborated axonal terminals (termed arbors), we assessed the spatial and morphological patterns of arbors from PSNs innervating the quadriceps (Quad) and adductor (Add) muscle groups (supplied by Obturator nerve [Obt]). We found that the arbors of Quad and Obt PSNs exhibit muscle-specific morphologies and spatial arrangements consistent with their target MN locations. PSNs also make connections with multiple spinal interneurons, including Renshaw cells (RCs), which are inhibitory interneurons that regulate the output of MNs. In contrast to the stretch reflex circuit, little is known about the organization of PSN contacts on RCs. Therefore, we mapped the connectivity pattern between RCs and PSNs from Quad and Obt afferents. We found that, although some RCs were selectively contacted by afferents from only one nerve, others received convergent input from both nerves. Interestingly, we found RCs with different connectivity patterns appear to be enriched in distinct regions of the ventral cord. During development, PSNs continually experience patterned neural activity. Though the importance of neural activity in remodeling neural circuits has been demonstrated in multiple systems, whether it affects development of PSN arbors or PSN-RC circuits remains unknown. Using an existing transgenic mouse model in which synaptic transmission of all PSNs was blocked, we found that synaptic activity blockage generally decreased the elaboration of PSN arbors without affecting their spatial organization. We also found that activity blockage decreased the probability that RCs receive any sensory input.

Page Count

146

Department or Program

Biomedical Sciences

Year Degree Awarded

2018

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