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Neuromodulation shapes motor output at all levels of neural processing

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Dirk Bucher, PhD

Associate Professor

Federated Department of Biological Sciences
New Jersey Institute of Technology and Rutgers University-Newark

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听A detailed and realistic quantitative understanding of neural circuit function is difficult for two reasons. First, despite similar activity patterns, underlying circuit component properties (like the expression levels of specific ion channels in specific cell types or the strength of synapses) can vary substantially across individuals. Second, circuit activity is critically dependent on the presence of neuromodulators. A multitude of substances like biogenic amines and neuropeptides sculpt circuit activity by tuning the properties of ion channels and synapses, most often through G protein-coupled receptors and second messenger signaling. Although the influence of neuromodulators on ion-channel and synaptic currents has been extensively studied and there is also broad understanding of how neuromodulators change the output of neural circuits, systems and even behavior, the mechanisms through which modulation of the components results in particular system outputs is much less understood.听Moreover, few studies have examined how neuromodulators, even those with overlapping or convergent actions, interact at the component or circuit level. Such an exploration requires a neural circuit whose anatomical connectivity is known and which can produce distinct and readily quantifiable output in the presence of different neuromodulators.

The pyloric circuit in the crustacean stomatogastric nervous system is one of the few systems that satisfies these requirements, and the rhythmic motor activity of this central pattern generating circuit has served for decades as a testbed for understanding the organizing principles of circuit activation. In our efforts towards a quantitative understanding of circuit activation, our recent work shows modulation at all levels of processing, including intrinsic excitability, synapse function, axonal action potential conduction, and muscle activation. Importantly, the complex patterns of convergence and divergence of co-modulator effects are modulator- and cell type-specific. Convergent co-modulation can be either mostly linearly additive or exhibit substantial nonlinearities. In the first case, convergent modulation can actually serve to reduce variability, i.e. ensure consistent circuit responses across individuals in the face of variability of baseline excitability and synaptic strengths. Finally, we also have started to show that neuromodulator signaling itself is subject to ligand- and activity-dependent long-term regulation to ensure stable responses.