Electrical stimulation induces synaptic changes in the peripheral auditory system

Abstract

Since a rapidly increasing number of neurostimulation devices are used clinically to modulate specific neural functions, the impact of electrical stimulation on targeted neural structure and function has become a key issue. In particular, the specific effect of electrical stimulation via a cochlear implant (CI) on inner hair cell (IHC) synapses remains unclear. Importantly, CI candidacy has recently expanded to include patients with partial hearing loss. Unfortunately, some CI recipients experience progressive hearing loss after activation of electrical stimulation. The mechanism(s) accounting for loss of residual hearing following electrical stimulation is unknown. Here normalhearing guinea pigs were implanted with customized CIs. Intracochlear electrical stimulation with an intensity equal to or above electrically evoked compound action potential (ECAP) threshold decreased the excitability of auditory nerve. Furthermore, the number of synapses between IHCs and the afferent spiral ganglion neurons (SGNs) also decreased after electrical stimulation with higher intensities. However, no significant change was observed in the packing density and perikaryal area of SGNs as well as the quantity of hair cells. These results carry important implications for use of CIs in patients with residual hearing and for an increasing number of patients treated with other neurostimulation devices. Notably, the results were based on acute electrical stimulation. Considering the complex interaction between CIs and targeted tissues, it is urgent to conduct further research to clarify whether the similar changes could be induced by chronic electrical stimulation.

The sensitivity of different methods for detecting abnormalities in auditory nerve function

“…Previous research from our laboratory has shown that the continuous stimulation of charge-balanced biphasic pulses to the cochlea can significantly elevate the ECAP threshold in guinea pigs [23]. These findings indicate that acute electrical stimulation (ES) has an inhibitive effect on the excitability of the auditory nerve.…”

Longitudinal Electrocochleography as an Objective Measure of Serial Behavioral Audiometry in Electro-Acoustic Stimulation Patients

“…In general, animal histology has suggested many possible etiologies, such as compromised endocochlear potentials (Tanaka et al 2014; Reiss et al 2015), cochlear neuropathy/synaptopathy (Li et al 2020), and excitotoxicity (Kopelovich et al 2015). A common theme is that these studies in general do not implicate hair cell / neural damage / pre-synaptic / post-synaptic damage (O’Leary et al 2013; Tanaka et al 2014; Reiss et al 2015; Quesnel et al 2016).…”

“…Histological data have also suggested compromised endocochlear potentials (Tanaka et al 2014; Reiss et al 2015) while not implicating hair cell / neural damage. Hair cell, neural, pre-synaptic ribbon counts, and post-synaptic receptor counts are stable post-loss of acoustic hearing (O’Leary et al 2013; Tanaka et al 2014; Reiss et al 2015; Quesnel et al 2016; but see Li et al 2020 who reported cochlear neuropathy/synaptopathy).…”

Light sheet microscopy of the gerbil cochlea

“…Here, using LSFM of the gerbil cochlea, we demonstrate that the cochlea's three‐dimensional frequency structure can be preserved, displayed, and measured. These measures are of great interest to physiologists investigating the cellular origins of the complex waveforms generated by the cochlea in response to acoustic (e.g., Forgues et al, 2014; Pappa et al, 2019) or electrical (e.g., Li, Lu, Zhang, Hansen, & Li, 2020; Wiegner, Wright, & Vollmer, 2016) stimuli, for monitoring changes in intracochlear pressure levels at defined frequency locations (e.g., Kale & Olson, 2015) and for interpreting the results of cochlear implant studies (e.g., Ahmad et al, 2012; Canfarotta et al, 2020; DeMason et al, 2012; Stakhovskaya, Sridhar, Bonham, & Leake, 2007). Typically, electrocochleographic recordings are taken from the RW in gerbils (e.g., Batrel et al, 2017; Fontenot, Giardina, & Fitzpatrick, 2017; Forgues et al, 2014; He, Porsov, Kemp, Nuttall, & Ren, 2012; Henry, 1995) as well as for other species including human—recently becoming a common metric for evaluating insertion damage and outcomes in cochlear implant patients (e.g., Abbas, Tejani, Scheperle, & Brown, 2017; Adunka et al, 2016; Campbell et al, 2016; Choudhury et al, 2012; Fontenot et al, 2019; Giardina et al, 2018; Giardina et al, 2019; Riggs et al, 2017; Scott et al, 2016).…”

“…Here, using LSFM of the gerbil cochlea, we demonstrate that the cochlea's three-dimensional frequency structure can be preserved, displayed, and measured. These measures are of great interest to physiologists investigating the cellular origins of the complex waveforms generated by the cochlea in response to acoustic (e.g., Forgues et al, 2014;Pappa et al, 2019) or electrical (e.g., Li, Lu, Zhang, Hansen, & Li, 2020;Wiegner, Wright, & Vollmer, 2016) stimuli, for monitoring changes in intracochlear pressure levels at defined frequency locations (e.g., Kale & Olson, 2015) F I G U R E 1 8 Application of the three-dimensional frequency map for geometry based physiological investigations. Frequency maps from otic capsule intact specimens retain relationships with external structures, as viewed from the apex (a) or laterally (b).…”