Research: Consequences of Electrical Activity on Spiral Ganglion Neuron (SGN) Axon Growth and Cochlear Intervention

Marlan Hansen, MD

The focus of our lab, which is supported by a grant from the National Institute on Deafness and Other Communication Disorders (NIDCD), is to determine the effects of electrical activity on spiral ganglion neuron (SGN) axon growth and the innervation of the cochlea. This includes determining the necessity of activity dependent signals to mediate the effects of electrical activity. Most types of sensorineural hearing loss result from damage to the hair cell accompanied by primary or secondary damage to the SGNs. Cochlear implants rehabilitate the most severe forms of sensorineural hearing loss by providing direct stimulation to the SGNs. Electrical activity regulates axon growth, and innervation patterns in many neurons. Thus, the consequence of electrical stimulation on SGN axon growth carries important implications for cochlear development, regeneration and implantation.

Membrane depolarization Ca2+/calmodulin dependent kinase II (CaMKII) activity, and protein kinase A (PKA) activity inhibits SGN axon growth. We hypothesize that electrical stimulation inhibits SGN axon growth by activating CaMKII and/or PKA. The first aim of this proposal is to define the effects of membrane electrical activity on SGN axon growth and the development of cochlear innervation by providing direct electrical stimulation to SGN in dissociated cultures and in cochlear slices. Secondly, we will determine the requirement of CaMKII and PKA activity for the inhibition of axon growth by depolarization and their role in the development of afferent cochlear innervation.

Constitutively active CaMKII and PKA mutants and transgene excoding highly specific CaMKII and PKA peptide inhibitors will be introduced into SGN in dissociated cultures and in cochlear slices to test the role of these molecules on SGN axon growth and cochlear innervation. The results of these studies will provide critical data on the consequences of electrical activity on SGN axon growth and cochlear innervation.