Sensorimotor Integration in a Small Motor Circuit

Rhythmic motor patterns, which underlie behaviors such as mastication, respiration and locomotion, are generated by specialized neural circuits called central pattern generators (CPGs). Although CPGs can generate their rhythmic motor output in the absence of rhythmic input, these motor patterns are modified by rhythmic sensory feedback in vivo. Furthermore, although the importance of sensory feedback in shaping CPG output is well known, most systems lack the experimental access needed to elucidate the mechanisms underlying sensorimotor integration at the cellular and synaptic level. I am therefore examining this issue using the gastric mill CPG, a circuit which generates the rhythmic retraction and protraction motor activity that drives chewing by the teeth in the gastric mill compartment of the crustacean stomach. The gastric mill CPG is well defined and very accessible at the cellular level. Specifically, I am examining the mechanism by which the gastropyloric receptor (GPR), a phasically active proprioceptor, selectively prolongs one phase (retraction) of the gastric mill rhythm in the isolated nervous system when it is activated in a pattern that mimics its in vivo activity. I first demonstrate that GPR regulation of the gastric mill rhythm relies on its presynaptic inhibition of modulatory commissural neuron 1 (MCN1), a projection neuron that activates and drives this rhythm. I also demonstrate that the GPR inhibition of MCN1 regulates the gastric mill rhythm by selectively regulating peptidergic cotransmission by MCN1. Lastly, I demonstrate that a peptide hormone (crustacean cardioactive peptide) that only modestly modifies the gastric mill rhythm, strongly gates the GPR regulation of this rhythm. Mechanistically, it acts not by influencing GPR or MCN1, but by activating the same excitatory current in the CPG neuron LG (lateral gastric) that is activated by MCN1-released peptide. This novel gating mechanism reduces GPR control over the amplitude of this excitatory current in LG. Thus, I have identified specific cellular mechanisms by which (a) phase-specific regulation of an ongoing motor pattern by a sensory input is accomplished, and (b) hormonal modulation gates that sensory input. These events are likely to reflect comparable ones occurring in the larger and less accessible vertebrate CNS. Degree Type Dissertation Degree Name Doctor of Philosophy (PhD) Graduate Group Neuroscience First Advisor Michael Nusbaum