40-Hz chirp auditory stimulation alleviates chronic restraint stress-induced depression-like behaviors and restores disrupted gamma oscillations.

Psychiatric disorders are increasingly treated using frequency-specific neuromodulation approaches. Our previous studies demonstrated impaired 40-Hz gamma oscillations in the temporal lobe of both patients with depression and depression-like animal models. Given that 40-Hz auditory stimulation can elicit robust frequency-specific neural responses in the auditory cortex, it may provide a contact-free means of modulating temporal-lobe gamma oscillations. Accordingly, this study aimed to establish a 40-Hz chirp auditory stimulation protocol and examine its effects on depression-like behaviors and gamma-band neural activity in a chronic restraint stress (CRS) rat model, providing a convenient intervention strategy for depression. Twenty-four rats were randomly assigned to a control group (n = 8) or a CRS group (n = 16), with CRS rats further receiving either 40-Hz chirp stimulation or sham stimulation for five consecutive days (20 min/day). Behavioral assessments were performed, followed by bilateral local field potential (LFP) recordings in the primary auditory cortex (A1). Results showed that 40-Hz chirp stimulation effectively alleviated CRS-induced depression- and anxiety-like behaviors, as reflected by increases in the sucrose preference index (SPI) and open-arm time. It selectively restored CRS-induced reductions in right A1 gamma activity, including task-rest gamma modulation, task-related narrowband gamma power and theta-gamma coupling. Moreover, right A1 gamma measures were significantly correlated with SPI, suggesting that the restoration of gamma oscillatory activity may underlie improvements in depression-like behavior. In summary, 40-Hz chirp stimulation alleviates depression-like behavior in CRS rats and modulates gamma-related neural activity, supporting its potential as a non-invasive neuromodulation strategy for depression.