Collaborative Research: Diversity of modulation and functional flexibility in small neuronal networks: An evolutionary and mechanistic approach

Rhythmic movements, such as heartbeat and locomotion, must be flexible to allow animals to alter their behavior in response to changing conditions. Rhythmic movements are controlled by networks of nerve cells that interact with one another to produce patterns of nerve impulses that drive appropriate muscle movements. To alter movement patterns, these neural networks rely on the actions of chemical compounds called neuromodulators; these compounds alter (modulate) the properties and interactions of the cells in the network, thereby enabling them to alter the pattern of movements that are generated by the network.

Such alterations include, for example, changes in the speed of the resulting behavior or the coordination of muscles that control different portions of the movement pattern. There is evidence, however, that the extent to which similar networks can be altered ("modulatory capacity") varies among species. This project addresses two fundamental questions related to this variability in modulatory capacity: first, on an evolutionary timescale, what variables determine the extent to which networks can be modulated, and second, what factors/mechanisms underlie differences in modulatory capacity.

In addition to addressing these questions using as exemplars the stomatogastric network and the cardiac network in a crab that eats only kelp versus a crab that eats many different kinds of food, the current project also prepares the next generation of scientists by (1) training high school students and undergraduates in a variety of research techniques, as well as in designing experiments and in analyzing and presenting data, and (2) providing continuity and potential expansion of the neuroscience component of a program that engages 7th grade Native Americans in Maine in science to enhance their educational aspirations and success in high school and beyond.

This project uses the stomatogastric and cardiac networks of closely related majoid crab species with vastly different dietary diversity to test the hypothesis that modulatory capacity is an important evolutionary substrate for diversity within any given behavior, and to ask what mechanisms underlie differences in modulatory capacity. Current data suggest that the stomatogastric network in Pugettia producta, a species that eats only kelp, is not responsive to many modulators that alter the network in another majoid, Libinia emarginata, which has a highly diverse diet.

This project expands the number of neuromodulators tested, as well as examines and compares modulation of the cardiac network in the same species. The investigators use transcriptomics and mass spectrometry to identify native isoforms of peptide modulators in these majoids, then use physiological recordings to compare the modulatory capacities of the Pugettia and Libinia stomatogastric and cardiac neuromuscular systems.

The prediction is that modulatory capacity in the Pugettia stomatogastric system is less than that of the opportunistic feeder, but that modulation in systems that are presumably subject to similar demands for flexibility, e.g., the cardiac neuromuscular system, is not markedly different. To examine the mechanisms that underlie changes in modulatory capacity, the investigators use transcriptomics, testing the hypothesis that the mechanism underlying decreased modulatory capacity of the Pugettia stomatogastric system is an absence or decreased abundance of receptors to those modulators.

Transcriptomics results are confirmed using qRT-PCR and through expression of the receptors of the two species to compare relative binding affinities.

This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.