Cellular Regulation of Neuronal Branching: A Day in the Life of a Growth Cone

Abstract

What are the cellular mechanisms that govern when the outgrowing neurite of a neuron will branch? This research analyzed one possible biochemical pathway through which environmental and cellular signals are transduced into physical (motor) changes within the growth cone of an outgrowing neuronal process, and how this pathway might be linked to the probability of branching. The system used for these studies was the buccal nervous system of the pond snail, Helisoma trivolvis. Specifically, this research investigated the effects of stimulating the intracellular signaling cascades mediated by cyclic-AMP-dependent protein kinase A (PKA) by injecting individual Helisoma neurons, isolated into primary cell culture, with analogs of cyclic-AMP. Analogs used for these studies were either activators or inactivators of cyclic-AMP-dependent PKA. This research showed that activating cyclic-AMP-dependent PKA increased the likelihood of neuritic branching, and inactivating PKA had variable effects on the capacity of a neurite to branch depending upon the specific neuronal identity. Because this data suggests an optimal range of PKA activity within which a growth cone might branch, we present a model for the complex relationship between PKA activity, intracellular calcium, and changes in neuronal architecture.