5‐HT1A and 5‐HT1B receptors differentially modulate rate and timing of auditory responses in the mouse inferior colliculus

Serotonin (5‐hydroxytryptamine; 5‐HT) is a physiological signal that translates both internal and external information about behavioral context into changes in sensory processing through a diverse array of receptors. The details of this process, particularly how receptors interact to shape sensory encoding, are poorly understood. In the inferior colliculus, a midbrain auditory nucleus, 5‐HT1A receptors have suppressive and 5‐HT1B receptors have facilitatory effects on evoked responses of neurons. We explored how these two receptor classes interact by testing three hypotheses: that they (i) affect separate neuron populations; (ii) affect different response properties; or (iii) have different endogenous patterns of activation. The first two hypotheses were tested by iontophoretic application of 5‐HT1A and 5‐HT1B receptor agonists individually and together to neurons in vivo . 5‐HT1A and 5‐HT1B agonists affected overlapping populations of neurons. During co‐application, 5‐HT1A and 5‐HT1B agonists influenced spike rate and frequency bandwidth additively, with each moderating the effect of the other. In contrast, although both agonists individually influenced latencies and interspike intervals, the 5‐HT1A agonist dominated these measurements during co‐application. The third hypothesis was tested by applying antagonists of the 5‐HT1A and 5‐HT1B receptors. Blocking 5‐HT1B receptors was complementary to activation of the receptor, but blocking 5‐HT1A receptors was not, suggesting the endogenous activation of additional receptor types. These results suggest that cooperative interactions between 5‐HT1A and 5‐HT1B receptors shape auditory encoding in the inferior colliculus, and that the effects of neuromodulators within sensory systems may depend nonlinearly on the specific profile of receptors that are activated.