Nicholas David DeLong - US grants

[unreadable] DESCRIPTION (provided by applicant): The goal of this research is to investigate the cellular mechanisms by which dynamic sensory feedback regulates the production of a rhythmic motor pattern. This work will focus on the gastric mill central pattern generator (CPG), which generates the rhythmic motor pattern that underlies chewing in the stomach of the crab Cancer borealis. Although some insight has been gained into the functional roles of particular sensory afferents in other rhythmic motor systems, little is known in any system about the cellular mechanisms that underlie such sensorimotor integration. I therefore aim to utilize the well characterized gastric mill CPG, which thus far has largely been studied in isolation from sensory feedback, to investigate the cellular mechanisms by which such feedback regulates motor pattern generation. Insofar as, I aim to identify and characterize the synaptic actions of identified sensory systems onto their motor circuit targets, including the contribution of divergent cotransmitter actions from these sensory neurons, this proposal will also contribute significantly to the understanding of how cotransmission contributes to the flexibility of neuronal function. Thus, I aim to first characterize the cellular and synaptic mechanisms by which an identified proprioceptor regulates the gastric mill CPG. This will include determining whether this proprioceptor regulation is mediated entirely by a single cotransmitter. Because an important feature of all CPGs is functional flexibility, I will also determine whether the cellular mechanisms underlying this proprioceptor-mediated regulation vary during the production of different gastric mill rhythms. In this context, I aim to document that this regulation involves a different cotransmitter when a distinct rhythm is being generated by the gastric mill circuit. Finally, I will coordinately activate two functionally distinct proprioceptors to determine the consequences of convergence of multiple sensory inputs onto the same CPG, at both the cellular and circuit output levels. By performing these experiments in a well-characterized, experimentally accessible system, I hope to gain insights into the mechanisms of sensorimotor integration that will provide insight towards general strategies for sensorimotor integration in all rhythmic motor systems. Given the extensive work that has documented the conservation of cellular and synaptic mechanisms underlying CPG generation in all animals, the results of this proposal are likely to resonate with comparable events occurring in the numerically larger and less accessible mammalian motor systems. Elucidating the cellular mechanisms underlying sensorimotor integration will thereby also contribute to an understanding of dysfunctional states as occur after stroke and spinal cord injury. [unreadable] [unreadable] [unreadable]