Resilience of Neurons and Circuits

The goal of the present proposal is to understand long-term neuronal and circuit stability and resilience in response to predictable and unpredictable temperature extremes. The proposed work is a direct outcome of years of computational and experimental work using the small circuits of the crustacean stomatogastric ganglion (STG), but addresses general problems relevant to all nervous systems, whether they are found in crabs or humans. Computational and experimental data show that there are many different sets of the parameters (degenerate solutions) that determine intrinsic excitability and synaptic strength that can produce extremely similar circuit outputs. This raises the question of whether animals, or humans, with different sets of circuit parameters can respond reliably to perturbations. Recordings from the pyloric rhythm of the STG show that all crabs show robust pyloric rhythms over permissive ranges of temperatures, or in response to modest changes in pH, and salinity. Nonetheless, more extreme perturbations elicit disrupted rhythms, or “crashes”, akin to what is seen in individuals who suffer from several neurological disorders. These changes are not visible under control temperatures, but are hidden, or cryptic, until the circuits are perturbed. Likewise, treatments with high potassium disrupt rhythms, but also induce cryptic states. Experiments to elucidate the factors that determine circuit resilience and how long-term experience evoke cryptic states will include acclimation of animals to various temperature regimes, measurement of STG motor patterns and neuromuscular junctions as a function of temperature and neuromodulators, as well as molecular characterization of gene expression and hemolymph composition.