Social interaction requires that relevant sensory information is collected, classified, and distributed to the motor areas that initiate an appropriate behavioral response. Vocal exchanges, in particular, depend on linking auditory processing to an appropriate motor expression. Because of its role in integrating sensory information for the purpose of action selection, the amygdala has been implicated in social behavior in many mammalian species. Here, we show that two nuclei of the extended amygdala play essential roles in vocal communication in the African clawed frog, Xenopus laevis. Transport of fluorescent dextran amines identifies the X. laevis central amygdala (CeA) as a target for ascending auditory information from the central thalamic nucleus and as a major afferent to the vocal pattern generator of the hindbrain. In the isolated (ex vivo) brain, electrical stimulation of the CeA, or the neighboring bed nucleus of the stria terminalis (BNST), initiates bouts of fictive calling. In vivo, lesioning the CeA of males disrupts the production of appropriate vocal responses to females and to broadcasts of female calls. Lesioning the BNST in males produces an overall decrease in calling behavior. Together, these results suggest that the anuran CeA evaluates the valence of acoustic cues and initiates socially appropriate vocal responses to communication signals, whereas the BNST plays a role in the initiation of vocalizations.

SUMMARYNeuromodulation by serotonin (5-HT) could link behavioral state and environmental events with sensory processing. Within the auditory system, the presence of 5-HT alters the activity of neurons in the inferior colliculus (IC), but the conditions that influence 5-HT neurotransmission in this region of the brain are unknown. We used in vivo voltammetry to measure extracellular 5-HT in the IC of behaving mice to address this issue. Extracellular 5-HT increased with the recovery from anesthesia, suggesting that the neuromodulation of auditory processing is correlated with the level of behavioral arousal. Awake mice were further exposed to auditory (broadband noise), visual (light) or olfactory (2,5-dihydro-2,4,5-trimethylthiazoline, TMT) stimuli, presented with food or confined in a small arena. Only the auditory stimulus or restricted movement increased the concentration of extracellular 5-HT in the IC. Changes occurred within minutes of stimulus onset, with the auditory stimulus increasing extracellular 5-HT by an average of 5% and restricted movement increasing it by an average of 14%. These findings suggest that the neuromodulation of auditory processing by 5-HT is a dynamic process that is dependent on internal state and behavioral conditions.

The neuromodulator serotonin regulates auditory processing and can increase within minutes in response to stimuli like broadband noise as well as non-auditory stressors. Little is known about the serotonergic response in the auditory system to more natural stimuli such as social interactions, however. Using carbon-fiber voltammetry, we measured extracellular serotonin in the auditory midbrain of resident male mice during encounters with a male intruder. Serotonin increased in the inferior colliculus (IC) over the course of a 15 minute interaction, but not when mice were separated with a perforated barrier. Several behaviors, including the amount of immobility and anogenital investigation performed by the resident, were correlated with the serotonergic response. Multiple intrinsic factors associated with individual mice also correlated with the serotonergic response. One of these was age: older mice had smaller serotonergic responses to the social interaction. In a second interaction, individual identity predicted serotonergic responses that were highly consistent with those in the first interaction, even when mice were paired with different intruders. Serotonin was also significantly elevated in the second social interaction relative to the first, suggesting a role for social experience. These findings show that during social interaction, serotonin in the IC is influenced by extrinsic factors such as the directness of social interaction and intrinsic factors including age, individual identity, and experience.

Context-dependent plasticity in auditory processing is achieved in part by physiological mechanisms that link behavioral state to neural responses to sound. The neuromodulator serotonin has many characteristics suitable for such a role. Serotonergic neurons are extrinsic to the auditory system but send projections to most auditory regions. These projections release serotonin during particular behavioral contexts. Heightened levels of behavioral arousal and specific extrinsic events, including stressful or social events, increase serotonin availability in the auditory system. Although the release of serotonin is likely to be relatively diffuse, highly specific effects of serotonin on auditory neural circuitry are achieved through the localization of serotonergic projections, and through a large array of receptor types that are expressed by specific subsets of auditory neurons. Through this array, serotonin enacts plasticity in auditory processing in multiple ways. Serotonin changes the responses of auditory neurons to input through the alteration of intrinsic and synaptic properties, and alters both short- and long-term forms of plasticity. The infrastructure of the serotonergic system itself is also plastic, responding to age and cochlear trauma. These diverse findings support a view of serotonin as a widespread mechanism for behaviorally relevant plasticity in the regulation of auditory processing. This view also accommodates models of how the same regulatory mechanism can have pathological consequences for auditory processing.