Maintenance of Neuronal Activity by Electrical Stimulation of Unilaterally Deafened Cats Demonstrable with Cytochrome Oxidase Technique

Trophic Support of Cultured Spiral Ganglion Neurons by Depolarization Exceeds and Is Additive with that by Neurotrophins or cAMP and Requires Elevation of [Ca2+]iwithin a Set Range

“…Direct electrical stimulation is sufficient to promote survival of deafferented SGNs in vivo (Wong-Riley et al, 1981;Lousteau, 1987;Hartshorn et al, 1991;Leake et al, 1991Leake et al, , 1992Lustig et al, 1994). The present study, using an in vitro model, support the hypothesis that membrane electrical activity attributable to presynaptic input is a crucial source of trophic support for SGNs.…”

“…In addition, presynaptic cells can provide neurotrophic support by causing depolarization through synaptic activity or by releasing neurotransmitters that activate trophic second messenger systems. The cochlea is well suited as a system for study of the means by which presynaptic input contributes to neuronal survival, because the SGNs are relatively accessible to in vivo experimental manipulations, including deafferentation and direct electrical stimulation (Wong-Riley et al, 1981;Lousteau, 1987;Hartshorn et al, 1991;Leake et al, 1991Leake et al, , 1992Lustig et al, 1994).…”

Multiple Distinct Signal Pathways, Including an Autocrine Neurotrophic Mechanism, Contribute to the Survival-Promoting Effect of Depolarization on Spiral Ganglion NeuronsIn Vitro

“…SGNs have only a single presynaptic input (the hair cells), which are selectively killed by aminoglycoside antibiotics. Electrical stimulation of such deafferented SGNs through implanted electrodes promotes their survival (Wong-Riley et al, 1981;Lousteau, 1987;Hartshorn et al, 1991;Leake et al, 1991Leake et al, , 1992Lustig et al, 1994). This is reflected in support of cultured SGNs by depolarization, allowing parallel in vivo and in vitro studies on a single system.…”

“…Spiral ganglion neurons (SGNs) die after deafferentation because of loss of hair cells (Spoendlin, 1975;Webster and Webster, 1981;Koitchev et al, 1982;Bichler et al, 1983). Electrical stimulation via an electrode implanted in the cochlea promotes survival of deafferented SGNs (Wong-Riley et al, 1981;Lousteau, 1987;Hartshorn et al, 1991;Leake et al, 1991Leake et al, , 1992Lustig et al, 1994), supporting a role for membrane electrical activity in SGN survival.…”

Early UCSF contributions to the development of multiple-channel cochlear implants

“…In 1976, the anatomist Patricia Leake joined our team and extended these studies with the support of Sheila Walsh Walsh et al, 1980), ultimately showing that chronic chargebalanced stimulation with scala tympani-implanted devices did not have major deleterious impacts re the survival of 8th nerve ganglion cells in deafened animals. In the same mid-1970's period, a study led by Dr. Margaret Wong-Riley also showed that chronic electrical stimulation had positive metabolic trophic impacts for brain stem auditory nuclei (Wong-Riley et al, 1981), an outcome later extended by Dr. Leake and colleagues (Leake et al, 1999(Leake et al, , 2013. On the basis of these more recent studies, we now know that there are generally largely neutral or positive consequences of the forms of chronic stimulation applied in CIs, for both the auditory nerve and brain stem.…”