Distribution of Metabotropic Serotonin Receptors in GABAergic and Glutamatergic Neurons in the Auditory Midbrain

ABSTRACT 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 serotonin receptors and the identity of neurons that express serotonin receptors in the IC remain unclear. Here, we hypothesized that IC GABAergic and glutamatergic neurons differentially express serotonin 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 serotonin 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 serotonin receptors. In contrast, a larger proportion of GABAergic neurons express excitatory serotonin receptors. Our data suggest that serotonin likely 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 serotonin receptors may help shape the balance of excitation and inhibition in the auditory midbrain, affecting sound processing.