Characterization of Anxiety-Like Behaviors and Neural Circuitry following Chronic Moderate Noise Exposure in Mice

Abstract

Background: Commonly encountered nontraumatic, moderate noise is increasingly implicated in anxiety; however, the neural substrates underlying this process remain unclear. Objectives: We investigated the neural circuit mechanism through which chronic exposure to moderate-level noise causes anxiety-like behaviors. Methods: Mice were exposed to chronic, moderate white noise [85 decibel (dB) sound pressure level (SPL)], 4 h/d for 4 wk to induce anxiety-like behaviors, which were assessed by open field, elevated plus maze, light-dark box, and social interaction tests. Viral tracing, immunofluorescence confocal imaging, and brain slice patch-clamp recordings were used to characterize projections from auditory brain regions to the lateral amygdala. Neuronal activities were characterized by in vivo multielectrode and fiber photometry recordings in awake mice. Optogenetics and chemogenetics were used to manipulate specific neural circuitry. Results: Mice chronically (4 wk) exposed to moderate noise (85 dB SPL, 4 h/d) demonstrated greater neuronal activity in the lateral amygdala (LA), and the LA played a critical role in noise-induced anxiety-like behavior in these model mice. Viral tracing showed that the LA received monosynaptic projections from the medial geniculate body (MG) and auditory cortex (ACx). Optogenetic excitation of the or circuits acutely evoked anxiety-like behaviors, whereas their chemogenetic inactivation abolished noise-induced anxiety-like behavior. Moreover, mice chronically exposed to moderate noise were more susceptible to acute stress, with more neuronal firing in the LA, even after noise withdrawal. Discussion: Mice exposed to 4 wk of moderate noise (85 dB SPL, 4 h/d) demonstrated behavioral and physiological differences compared to controls. The neural circuit mechanisms involved greater excitation from glutamatergic neurons of the MG and ACx to LA neurons under chronic, moderate noise exposure, which ultimately promoted anxiety-like behaviors. Our findings support the hypothesis that nontraumatic noise pollution is a potentially serious but unrecognized public health concern. https://doi.org/10.1289/EHP12532

Microglial activation in the lateral amygdala promotes anxiety‐like behaviors in mice with chronic moderate noise exposure

“…As prior chronic noise exposure can reportedly induce an acute stressor‐sensitive state in mice, 45 we also found that mice treated with chronic sound exposure exhibited no anxiety‐like behaviors after 28 days of noise withdrawal following chronic sound exposure (Figure 3A–C ). However, these noise‐treated mice indeed showed anxiety‐like symptoms upon exposure to a single 2‐h noise (85‐dB SPL) treatment after the 28‐day withdrawal compared to control animals (Figure 3D,E ).…”

“…This chronic noise exposure reliably elicits anxiety‐like behaviors in the open‐field test (OFT), elevated plus maze (EPM), and light–dark box, as reported recently by our laboratory. 45 In particular, in the OFT, noise‐exposed mice spent significantly less time in the open‐field center compared to control mice (Figure 1B,C ), with no difference in total travel distance (Figure 1D ). Similarly, noise‐exposed mice also spent less time in the open arms of the EPM (Figure 1E, F ), indicating an anxiety‐like response to noise.…”

“…In order to understand noise‐induced change of the LA neuronal activity, extracellular electrophysiology recordings were made in awake head‐fixed mice using silicon electrodes, as previously described. 45 The mice were mounted in the stereotaxic frame under isoflurane anesthesia, and a homemade headpost was cemented to the skull. For head fixation, the headpost was firmly fastened to a holder.…”

“…In this study, we developed a mouse model of chronic moderate noise‐induced anxiety by exposing mice to white noise at 85 dB SPL for 4 h daily for 28 days, which has been previously used to explore the non‐auditory effects of moderate noise exposure. 44 , 45 According to the 5‐dB exchange rate set by the Occupational Safety and Health Administration (OSHA), 46 a 4‐h exposure at 85 dBA (A‐weighted decibels) is as dangerous as 8 h at 80 dBA, below the 90 dBA of the permissible exposure limit in the occupational noise exposure and is a typical noise level of urban traffic. 47 We then examined microglia‐mediated synaptic remodeling in the LA of chronic moderate noise exposure mice.…”

Characterization of the neural circuitry of the auditory thalamic reticular nucleus and its potential role in salicylate-induced tinnitus

“…Subjective tinnitus, the perception of non-existent sounds, burdens an estimated 14% of adults globally, with potentially severe consequences including anxiety, depression, and, in extreme cases, suicide ( Rauschecker et al, 2010 ; Roberts et al, 2010 ; Leaver et al, 2011 ; Elgoyhen et al, 2015 ; Henton and Tzounopoulos, 2021 ; Peng et al, 2023 ). Despite its prevalence, there are currently no effective pharmaceutical treatments available for tinnitus ( Henton and Tzounopoulos, 2021 ).…”