Distribution of metabotropic serotonergic receptors in GABAergic and glutamatergic neurons in the auditory midbrain

The neurotransmitter serotonin modulates a variety of behavioral and physiological responses in the brain. Serotonergic neurons from the dorsal raphe nuclei send a dense projection to the auditory system, including the inferior colliculus (IC), the midbrain hub of the central auditory system. In the IC, serotonin alters how neurons respond to complex sounds, and it has been implicated in the generation or perception of tinnitus. However, the distribution of serotonergic receptors and the identity of neurons that express serotonergic receptors in the IC remains unclear. Here, we hypothesized that IC GABAergic and glutamatergic neurons differentially express serotonergic receptors. To test this hypothesis, we performed in situ hybridization in IC brain slices of male and female mice using probes for Vgat (GABAergic neuron marker) and Vglut2 (glutamatergic neuron marker), along with probes for six subtypes of metabotropic serotonergic receptors: 5-HT1 _A and 5-HT1 _B ( Htr1a and Htr1b, inhibitory, G _i/o G protein receptors), 5-HT2 _A , 5-HT2 _B and 5-HT2 _C ( Htr2a, Htr2b, and Htr2c excitatory, G _q11 G protein receptors) and, 5-HT7 (excitatory, G _s G protein receptors). Our data show that glutamatergic IC neurons primarily express inhibitory serotonergic receptors. In contrast, a larger proportion of GABAergic neurons express excitatory serotonergic receptors. Our data suggest that serotonin exerts an inhibitory net effect on IC neuronal circuits. These findings contribute to our understanding of how serotonin signaling influences auditory processing. The differential expression of serotonergic receptors may help shape the balance of excitation and inhibition in the auditory midbrain, affecting sound processing.