Investigating the Effect of Noise Exposure on Hippocampal‐Dependent Spatial Learning and Memory in a Rat Model

Abstract

Hearing loss is one of the most prevalent chronic health conditions worldwide, with excessive exposure to loud noise as a leading cause of hearing loss. Beyond the devastating effects of hearing impairment itself, epidemiological studies have identified hearing loss as a major risk factor for cognitive decline. Furthermore, preclinical studies on rodents have identified that the hippocampus—a brain region outside of the classical auditory pathway which subserves spatial navigation—appears to be vulnerable to noise exposure. For example, two hours of exposure to very loud noise (e.g., 123 dB sound pressure level, SPL) has been shown to cause long-term impairment in spatial learning and memory, as well as suppress hippocampal neurogenesis (i.e., the processes by which new neurons are generated from neural stem cells in the adult brain). That said, because these past studies used noise levels that far exceed those frequently experienced by humans who work in noisy environments, it remains uncertain whether a more modest degree of hearing loss, consistent with that caused by daily, occupational noise exposure, is also problematic for normal hippocampal function. In the present study, we are using a rat model to study the effect of daily noise exposure on spatial learning, memory and hippocampal neurogenesis. Following baseline hearing testing using the auditory brainstem response (i.e., an electrophysiologically-measured evoked potential from the brain in response to sound), 6-month old Fischer 344 rats were exposed to 100 dB SPL white noise (or silence) for 4 hours/day for 30 days. Separate cohorts of noise- and sham-exposed rats then underwent behavioral testing at 7, 10, or 13 months old using a Morris water maze (MWM) protocol to assess hippocampal-dependent spatial acquisition learning and reference memory. After completion of the behavioral testing and post-exposure hearing assessments, the rats were sacrificed, and their brains harvested for tissue processing. As predicted, the noise-exposed rats had a mild degree of high-frequency hearing loss, evidenced by a ~25 dB increase in the rats’ hearing threshold to a 20 kHz acoustic stimulus. Overall, both treatment groups demonstrated spatial acquisition learning over the 5 training days on the MWM hidden platform task; however, the noise-exposed rats performed slightly, albeit significantly worse than the shams at 10 months of age. Moreover, in contrast to past studies that used very loud noise exposures, none of the cohorts of noise-exposed rats in the present study were impaired during the MWM probe task; findings which identify that deficits in spatial reference memory are not an inevitable consequence of repeated exposure to sounds that cause a mild degree of hearing loss. Histological analysis of hippocampal neurogenesis is ongoing. Ultimately, given that not all individuals exposed to occupational noise suffer the same degree of hearing loss, it will be important that we correlate each rat's hearing sensitivity with its’ cognitive-behavioral performance and extent of hippocampal neurogenesis, so as to better understand the complex relationship between noise-induced hearing loss, cognitive impairment and neuropathology.