Variability, Neuromodulation and Robustness of Neurons and Networks

All individual humans and animals are different. How well-tuned do brains need to be to produce behavior that we consider healthy and normal? This question has been difficult to study rigorously in animals with large brains, but small nervous systems with identified neurons and circuits have allowed us to ask this question in the past few years. Experimental work on the crustacean stomatogastric ganglion (STG) has revealed a 2-6 fold variability in many of the parameters that are important for circuit dynamics. These include the strength of the same synapse across animals, as well as the conductance densities of many membrane currents and the copy numbers of the mRNA that encode those currents (Goaillard et al., Nat Neuroscience. 2009). At the same time, a body of theoretical work shows that the similar network performance can arise from diverse underlying parameter sets (Prinz et al., Nat Neuroscience 2004; Gutierrez and Marder, 2013). Together, these lines of evidence suggest that each individual animal has found a different solution to producing “good enough” motor patterns for healthy performance in the world. These findings raise the question of the extent to which animals with different sets of underlying circuit parameters can respond reliably and robustly to environmental perturbations and neuromodulation. Consequently, we studied the effects of temperature, pH and neuromodulation on the pyloric rhythm of crabs. Additionally, we have measured the anatomical features of identified neurons, and find that their anatomical variability is surprisingly accompanied by very reliable responses to focally applied glutamate applied at many places across their dendritic arbors, indicating that highly complex neurons are almost isopotential across major distances from the soma.