Using an appetitive operant conditioning paradigm to screen rats for tinnitus induced by intense sound exposure: Experimental considerations and interpretation

Sarah H Hayes; Krystal Beh; Marei Typlt; Ashley L Schormans; Daniel Stolzberg; Brian L Allman

doi:10.3389/fnins.2023.1001619

Using an appetitive operant conditioning paradigm to screen rats for tinnitus induced by intense sound exposure: Experimental considerations and interpretation

Front Neurosci. 2023 Feb 10:17:1001619. doi: 10.3389/fnins.2023.1001619. eCollection 2023.

Authors

Sarah H Hayes¹, Krystal Beh^{1

2}, Marei Typlt^{1

3}, Ashley L Schormans¹, Daniel Stolzberg⁴, Brian L Allman^{1

2}

Affiliations

¹ Department of Anatomy and Cell Biology, Schulich School of Medicine and Dentistry, The University of Western Ontario, London, ON, Canada.
² National Centre for Audiology, Elborn College, The University of Western Ontario, London, ON, Canada.
³ Audifon GmbH & Co. KG, Kölleda, Germany.
⁴ Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, The University of Western Ontario, London, ON, Canada.

Abstract

In an effort to help elucidate the neural mechanisms underlying tinnitus in humans, researchers have often relied on animal models; a preclinical approach which ultimately required that behavioral paradigms be designed to reliably screen animals for tinnitus. Previously, we developed a two-alternative forced-choice (2AFC) paradigm for rats that allowed for the simultaneous recording of neural activity at the very moments when they were reporting the presence/absence of tinnitus. Because we first validated our paradigm in rats experiencing transient tinnitus following a high-dose of sodium salicylate, the present study now sought to evaluate its utility to screen for tinnitus caused by intense sound exposure; a common tinnitus-inducer in humans. More specifically, through a series of experimental protocols, we aimed to (1) conduct sham experiments to ensure that the paradigm was able to correctly classify control rats as not having tinnitus, (2) confirm the time course over which the behavioral testing could reliably be performed post-exposure to assess chronic tinnitus, and (3) determine if the paradigm was sensitive to the variable outcomes often observed after intense sound exposure (e.g., hearing loss with our without tinnitus). Ultimately, in accordance with our predictions, the 2AFC paradigm was indeed resistant to false-positive screening of rats for intense sound-induced tinnitus, and it was able to reveal variable tinnitus and hearing loss profiles in individual rats following intense sound exposure. Taken together, the present study documents the utility of our appetitive operant conditioning paradigm to assess acute and chronic sound-induced tinnitus in rats. Finally, based on our findings, we discuss important experimental considerations that will help ensure that our paradigm is able to provide a suitable platform for future investigations into the neural basis of tinnitus.

Keywords: animal models; hearing loss; intense sound exposure; tinnitus; two-alternative forced-choice behavior.

Grants and funding

This research was supported in part by grants to BA from the Natural Sciences and Engineering Research Council of Canada (NSERC Discovery Grant 435819-2013 RGPIN), and the Canadian Institutes of Health Research (CIHR 137098), as well as a Canada First Research Excellence Fund BrainsCAN Postdoctoral Fellowship to SH.