Circuit-specific modulation by neuroactive peptides

Neuromodulators, whether neuronally released within the nervous system or released into the bloodstream as circulating hormones from neuroendocrine organs, alter the output of the nervous system. By changing the cellular and synaptic properties of their target neurons, these modulators produce functionally distinct circuits from a single network. The goal of this Thesis is to further elucidate how neuromodulators configure neuronal circuits and influence inter-circuit interactions to elicit the neuronal activity underlying different patterns of behavior. The stomatogastric nervous system of decapod crustaceans contains a set of distinct but interacting central pattern generating circuits that have been extensively characterized at the cellular level. The gastric mill (chewing) and pyloric (filtering) circuits, which are the best characterized of these circuits, are located in the stomatogastric ganglion (STG). The cellular and synaptic properties of each STG neuron are state dependent and are regulated by circulating hormones and the release of modulatory transmitters from a small number (\u3c20) of projection neurons. By characterizing the mechanisms by which two newly identified neurohormones, Pevkinin and Cabpyrokinin (CabPK), regulate the gastric mill and pyloric circuits, this Thesis describes novel ways in which motor patterns are selected from multifunctional networks. Chapter two documents that Pevkinin peptides selectively influence the pyloric circuit but, due to its strengthening of a particular synapse, only cause a modest increase in pyloric rhythm speed. Chapter three demonstrates that CabPK is present in this system and elicits the gastric mill rhythm without influencing the pyloric rhythm. Chapter four reveals that CabPK and the identified projection neuron MCN1 elicit similar gastric mill rhythms using distinct mechanisms, including differences in the interactions between the gastric mill and pyloric rhythms. In conclusion, the modulatory state of a network shapes both intra- and inter-circuit interactions and thereby influences circuit output. Moreover, neuromodulation can not only allow a single circuit to elicit more than one motor pattern, but it can enable more than one circuit to elicit a single motor pattern. By understanding the ways in which neuromodulators change circuit output and alter inter-circuit interactions, we make progress in understanding how neuronal circuits produce behavior