Serotonergic Modulation of Sensory Representation in a Central Multisensory Circuit Is Pathway Specific

Many studies have explored how neuromodulators affect synaptic function, yet little is known about how they modify computations at the microcircuit level. In the dorsal cochlear nucleus (DCN), a region that integrates auditory and multisensory inputs from two distinct pathways, serotonin (5-HT) enhances excitability of principal cells, predicting a generalized reduction in sensory thresholds. Surprisingly, we found that when looked at from the circuit level, 5-HT enhances signaling only from the multisensory input, while decreasing input from auditory fibers. This effect is only partially explained by an action on auditory nerve terminals. Rather, 5-HT biases processing for one input pathway by simultaneously enhancing excitability in the principal cell and in a pathway-specific feed-forward inhibitory interneuron. Thus, by acting on multiple targets, 5-HT orchestrates a fundamental shift in representation of convergent auditory and multisensory pathways, enhancing the potency of non-auditory signals in a classical auditory pathway. [Display omitted] •In a multisensory integrator, 5-HT readjusts the relative strength of different inputs•5-HT enhances excitability of principal cells and auditory input-driven interneurons•Principal cells then respond well to multisensory input, yet have weaker auditory drive•5-HT therefore operates at the microcircuit level to modulate sensory processing Neuromodulators may alter sensory processing upon changes in behavioral state. Tang and Trussell demonstrate that the neuromodulator serotonin shifts the representation of convergent auditory and multisensory pathways at a microcircuit level, enhancing the potency of non-auditory signals in a classical auditory brain region.