Modulation of auditory brainstem responses by serotonin and specific serotonin receptors

The neuromodulator serotonin is found throughout the auditory system from the cochlea to the cortex. Although effects of serotonin have been reported at the level of single neurons in many brainstem nuclei, how these effects correspond to more integrated measures of auditory processing has not been well-explored. In the present study, we aimed to characterize the effects of serotonin on far-field auditory brainstem responses (ABR) across a wide range of stimulus frequencies and intensities. Using a mouse model, we investigated the consequences of systemic serotonin depletion, as well as the selective stimulation and suppression of the 5-HT1 and 5-HT2 receptors, on ABR latency and amplitude. Stimuli included tone pips spanning four octaves presented over a forty dB range. Depletion of serotonin reduced the ABR latencies in Wave II and later waves, suggesting that serotonergic effects occur as early as the cochlear nucleus. Further, agonists and antagonists of specific serotonergic receptors had different profiles of effects on ABR latencies and amplitudes across waves and frequencies, suggestive of distinct effects of these agents on auditory processing. Finally, most serotonergic effects were more pronounced at lower ABR frequencies, suggesting larger or more directional modulation of low-frequency processing. This is the first study to describe the effects of serotonin on ABR responses across a wide range of stimulus frequencies and amplitudes, and it presents an important step in understanding how serotonergic modulation of auditory brainstem processing may contribute to modulation of auditory perception.