Patricia Leake

Research Interests

Morphological and electrophysiological studies of cochlear implants and auditory system development and plasticity

Research Summary

Our research falls into two separate but overlapping areas. Our developmental studies of the auditory system focus on elucidating the fundamental organization of the mammalian cochlear spiral ganglion, the primary afferent auditory projections to the brainstem cochlear nuclei, and the mechanisms and timing of development of the precise organization of this sensory pathway. This work employs a broad spectrum of morphometric, neuroanatomical tracer, cytochemical labeling and electron microscopic methods. Research goals include: 1) determining the specific sequence and timing of postnatal maturation of major anatomic features of the mammalian organ of Corti; 2) characterizing in parallel the timing and extent of refinement in connectional selectivity that occurs in the primary afferent projections to the brainstem cochlear nuclei and the ; 3) relating morphological findings to the emergence of spontaneous activity and specific functional properties of the spiral ganglion neurons and auditory nerve, in order to provide a better understanding of the role of neural activity in emergence of connectional selectivity.

A second major focus of our research is the development and safe application of multichannel cochlear prostheses. These studies are directed toward defining the anatomical and functional consequences of neonatal deafness and electrical stimulation of the cochlea during maturation, and modeling the current application of these cochlear implant in young, congenitally deaf children. Our studies in neonatally deafened animals have shown that chronic electrical stimulation from a cochlear implant provides neurotrophic support that promotes markedly improved survival of the spiral ganglion neurons, which otherwise degenerate after deafness. We have also examined the functional consequences of such chronic stimulation by characterizing the response properties of single neurons within the auditory midbrain, the inferior colliculus. This work on plasticity and optimizing cochlear implants dovetails with the developmental studies outlined above in current studies in which we are determining the effects of early deafness, direct delivery of neurotrophic agents (e.g., BDNF, NT-3 and JNK inhibitor) and specific formats of electrical stimulation delivered by an implant on the selectivity of the primary afferent connections to the cochlear nuclei.

Other studies focus on practical aspects of intracochlear electrode designs for human application. For example, human temporal bone studies of new designs of cochlear implants are evaluating the nature and extent of iinsertion trauma and the precise location of stimulating electrodes re: the target neurons.

Selected Publications

Leake PA, Snyder RL, Hradek GT. (2002) Postnatal refinement of auditory nerve projections to the cochlear nucleus in cats. J Comp Neurol 448(1):6-27.

Vollmer M, Leake PA, Beitel R, Rebscher SJ, Snyder RL. 2005. Degradation in temporal resolution in the auditory midbrain after prolonged deafness is reversed by electrical stimulation of the cochlea.  J. Neurophysiol. 93: 3339-3355.

Leake PA, Hradek GT, Chair L, Snyder RL. 2006. Neonatal deafness results in degraded topographic specificity (frequency resolution) of auditory nerve projections to the cochlear nucleus in cats.  J Comp Neurol 497:13-31

Leake PA, Hradek GT, Vollmer M, Rebscher SJ. 2007.  Neurotrophic Effects of GM1 Ganglioside and Electrical Stimulation on Cochlear Spiral Ganglion Neurons in Cats Deafened as Neonates.  J. Comp. Neurol. 501: 837-853.

Stakhovskaya O, Sridhar D, Bonham B, Leake PA.  2007. Frequency map for the human cochlear spiral ganglion:  Implications for cochlear implants.  JARO 8: 220-233. 

Jones TA, Leake PA, Snyder RL, Stakhovskaya O, Bonham BH.  (2007)  Spontaneous discharge patterns in cochlear spiral ganglion cells prior to the onset of hearing in cats.  J. Neurophysiol. 98(4):1898-1908.