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

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.