From behavioral context to receptors: serotonergic modulatory pathways in the IC.

In addition to ascending, descending, and lateral auditory projections, inputs extrinsic to the auditory system also influence neural processing in the inferior colliculus (IC). These types of inputs often have an important role in signaling salient factors such as behavioral context or internal state. One route for such extrinsic information is through centralized neuromodulatory networks like the serotonergic system. Serotonergic inputs to the IC originate from centralized raphe nuclei, release serotonin in the IC, and activate serotonin receptors expressed by auditory neurons. Different types of serotonin receptors act as parallel pathways regulating specific features of circuitry within the IC. This results from variation in subcellular localizations and effector pathways of different receptors, which consequently influence auditory responses in distinct ways. Serotonin receptors may regulate GABAergic inhibition, influence response gain, alter spike timing, or have effects that are dependent on the level of activity. Serotonin receptor types additionally interact in nonadditive ways to produce distinct combinatorial effects. This array of effects of serotonin is likely to depend on behavioral context, since the levels of serotonin in the IC transiently increase during behavioral events including stressful situations and social interaction. These studies support a broad model of serotonin receptors as a link between behavioral context and reconfiguration of circuitry in the IC, and the resulting possibility that plasticity at the level of specific receptor types could alter the relationship between context and circuit function.