Hyperactivity in the Ventral Cochlear Nucleus after Cochlear Trauma

Abstract

The emergence of hyperactivity in the form of elevated spontaneous firing rates after cochlear trauma has been well documented in a number of central auditory structures, including the auditory cortex, inferior colliculus, and dorsal subdivision of the cochlear nucleus. This hyperactivity is of interest as a possible neural substrate of tinnitus. Whether the ventral subdivision of the cochlear nucleus shows hyperactivity has never been investigated despite the fact that, like the dorsal division, it also receives direct input from the damaged cochlea and supplies major ascending inputs to brainstem and midbrain auditory centers. We investigated spontaneous neuronal firing rates in the ventral cochlear nucleus in a guinea pig model of cochlear trauma in which we have shown that hyperactivity consistently develops in the inferior colliculus (Mulders and Robertson, 2009). The mean spontaneous firing rates of ventral cochlear nucleus neurons was significantly elevated compared to sham controls. This hyperactivity was more evident in primary-like and onset categories of neurons. Hyperactivity in the ventral subdivision of cochlear nucleus therefore needs to be considered in relation to neural models of the genesis of tinnitus.

Brainstem Auditory Evoked Potentials Suggest a Role for the Ventral Cochlear Nucleus in Tinnitus

“…Recent neurophysiological data in animals supports the presence of increased SBC excitability following acoustic trauma, a common cause of tinnitus (Vogler et al 2011). In particular, elevated spontaneous activity was evident in the VCN, particularly in two VCN unit types, one of which (primary-like) corresponds to SBCs.…”

Effects of Unilateral Acoustic Trauma on Tinnitus-Related Spontaneous Activity in the Inferior Colliculus

“…5). Electrophysiological studies of the VCN have confirmed significant increases in spontaneous activity after acoustic trauma or mechanical lesions of the cochlea (Vogler et al 2011). Unit classifications based on the shape of peri-stimulus time histograms (PSTHs) linked the largest rate increases to primary-like units, which represent the physiological counterpart of SBCs.…”

“…In the context of existing neurophysiological models, DCN-based hyperactivity is expected to target type O units (Kaltenbach 2006;Robertson et al 2013). Conversely, VCN-based hyperactivity is directed toward type V and I units (Vogler et al 2011).…”

“…Because different neuron types are uniquely affected by acoustic trauma (Cai et al 2009), hyperactivity may be expressed in one output pathway of the cochlear nuclei, but not another. The dorsal cochlear nucleus (DCN) has received notable attention as a source of tinnitusrelated hyperactivity (Zhang and Kaltenbach 1998;Brozoski et al 2002), although similar patterns of neuropathology have been confirmed in the ventral cochlear nucleus (VCN) (Vogler et al 2011).…”

Ouabain-Induced Cochlear Nerve Degeneration: Synaptic Loss and Plasticity in a Mouse Model of Auditory Neuropathy

“…This is partially explained by considering that ABR thresholds (∼30 dB SPL) are significantly higher than single-fiber thresholds (∼0 dB SPL (Taberner and Liberman, 2005)); thus, an additional 10 dB increase to ∼40 dB SPL by impinging on the more broadly tuned portions of ANF tuning curves, rapidly recruits ANFs over large extents of the cochlear spiral. For ABRs, another contributing factor is that a peripheral neuropathy may enhance responses in the central auditory nuclei, such as cochlear nucleus and the inferior colliculus (Mulders and Robertson, 2009;Vogler et al, 2011), which contribute to the later waves that typically appear at lower SPLs than wave 1. Indeed, post-exposure decreases in ABR thresholds, without parallel changes in DPOAE thresholds, have been noted in the acoustic trauma model of neuropathy (Fig.…”