Neuronal Organization in the Inferior Colliculus Revisited with Cell-Type-Dependent Monosynaptic Tracing

The inferior colliculus (IC) is a critical integration center in the auditory pathway. However, because the inputs to the IC have typically been studied by the use of conventional anterograde and retrograde tracers, the neuronal organization and cell-type-specific connections in the IC are poorly understood. Here, we used monosynaptic rabies tracing and in situ hybridization combined with excitatory and inhibitory Cre transgenic mouse lines of both sexes to characterize the brainwide and cell-type-specific inputs to specific neuron types within the lemniscal IC core and nonlemniscal IC shell. We observed that both excitatory and inhibitory neurons of the IC shell predominantly received ascending inputs rather than descending or core inputs. Correlation and clustering analyses revealed two groups of excitatory neurons in the shell: one received inputs from a combination of ascending nuclei, and the other received inputs from a combination of descending nuclei, neuromodulatory nuclei, and the contralateral IC. In contrast, inhibitory neurons in the core received inputs from the same combination of all nuclei. After normalizing the extrinsic inputs, we found that core inhibitory neurons received a higher proportion of inhibitory inputs from the ventral nucleus of the lateral lemniscus than excitatory neurons. Furthermore, the inhibitory neurons preferentially received inhibitory inputs from the contralateral IC shell. Because IC inhibitory neurons innervate the thalamus and contralateral IC, the inhibitory inputs we uncovered here suggest two long-range disinhibitory circuits. In summary, we found: (1) dominant ascending inputs to the shell, (2) two subpopulations of shell excitatory neurons, and (3) two disinhibitory circuits.