Increasing GABA reverses age-related alterations in excitatory receptive fields and intensity coding of auditory midbrain neurons in aged mice

Abstract

A key feature of age-related hearing loss is a reduction in the expression of inhibitory neurotransmitters in the central auditory system. This loss is partially responsible for changes in central auditory processing, as inhibitory receptive fields play a critical role in shaping neural responses to sound stimuli. Vigabatrin (VGB), an antiepileptic agent that irreversibly inhibits γ-amino butyric acid (GABA) transaminase, leads to increased availability of GABA throughout the brain. This study used multi-channel electrophysiology measurements to assess the excitatory frequency response areas in old CBA mice to which VGB had been administered. We found a significant post-VGB reduction in the proportion of V-type shapes, and an increase in primary-like excitatory frequency response areas. There was also a significant increase in the mean maximum driven spike rates across the tonotopic frequency range of all treated animals, consistent with observations that GABA buildup within the central auditory system increases spike counts of neural receptive fields. This increased spiking is also seen in the rate-level functions and seems to explain the improved low-frequency thresholds.

Objective evidence of temporal processing deficits in older adults

“…The peaks of the ABR have sources from the auditory nerve through the inferior colliculus (IC); furthermore, the later peaks have multiple sources because of crossed auditory pathways (Kaga et al, 1997;Kuokkanen et al, 2018;Land et al, 2016;Møller and Jannetta, 1983). Aging may result in a loss of auditory nerve fibers, cochlear synaptopathy (Garrett and Verhulst, 2019;Makary et al, 2011;Schmiedt et al, 1996;Sergeyenko et al, 2013;Viana et al, 2015), and changes in neural coding in the auditory brainstem (Brecht et al, 2017;Parthasarathy et al, 2014;Schatteman et al, 2008;Williamson et al, 2015). Because ABR peak latencies are delayed and amplitudes are reduced by neuronal loss or by changes in synchronous firing patterns, the ABR may provide a sensitive measure of temporal processing in older individuals.…”

Sensorineural hearing loss and cognitive impairment: three hypotheses

“…GABA, however, is decreased in the auditory center of the temporal lobe in ARHL patients ( Zemaitis et al, 2021 ), which does not contradict the previous decrease in total GABA. Interestingly, it has been suggested that increasing GABA in the auditory cortex or increasing the sensitivity of GABA receptors enhances the response of the auditory center to sound stimuli ( Brecht et al, 2017 ). This reinforces the idea that HL causes a redistribution of CL, resulting in CI.…”