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

Abstract

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 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. Sound undergoes extensive processing in the brainstem. The inferior colliculus (IC) core is classically viewed as the integration center for ascending auditory information, whereas the IC shell integrates descending feedback information. Here, we demonstrate that ascending inputs predominated in the IC shell but appeared to be separated from the descending inputs. The presence of inhibitory projection neurons is a unique feature of the auditory ascending pathways, but the connections of these neurons are poorly understood. Interestingly, we also found that inhibitory neurons in the IC core and shell preferentially received inhibitory inputs from ascending nuclei and contralateral IC, respectively. Therefore, our results suggest a bipartite domain in the IC shell and disinhibitory circuits in the IC.

Organization of projection from brainstem auditory nuclei to the inferior colliculus of Japanese house bat (Pipistrellus abramus)

“…Furthermore, information conveyed by interconnecting LG and GLU cells is likely to be different since both cell types receive different combination of extrinsic inputs (Chen, Cheng, Ito, & Song, 2018) and LG cells receive inputs from GLU cells in different synaptic domains (Ito & Oliver, 2014). Based on studies on rodents, LG neurons integrate information from multiple brainstem nuclei, while GLU cells integrate inputs related to their synaptic domains (Chen et al., 2018; Ito & Oliver, 2014; Ito et al., 2015). Therefore, it is suggested that LG cells control the entire IC circuit according to global state of brainstem nuclei, while GLU cells control according to the state of specific pathways.…”

Different coding strategy of sound information between GABAergic and glutamatergic neurons in the auditory midbrain

“…A recent study has shown that GLU cells in different IC domains receive different combinations of extrinsic inputs, whereas GABAergic cells always receive a similar combination of extrinsic inputs (Chen et al . ). It has also been reported that some characteristics of sound besides characteristic frequency are coded in spatially organized ways inside the ICC (Schreiner & Langner, ; Rees & Langner, ).…”

“…Furthermore, a cell‐type‐specific monosynaptic retrograde tracing study revealed that inputs to GLU cells are related to their synaptic domain, whereas those to GABAergic cells are unrelated to the location of cell bodies and thus always similar (Chen et al . ). These results suggest that differences in the dendritic arborization and organization of presynaptic inputs underlie the different patterns of clustering for sound information between GLU and GABAergic neurons.…”

“…Current results strongly suggest that GLU cells receive inputs mainly from a small region of a fibrodendritic lamina, whereas GABAergic cells receive inputs from a wider region consisting of several fibrodendritic laminae, providing the basis for their different responsiveness to sound. Furthermore, a cell-type-specific monosynaptic retrograde tracing study revealed that inputs to GLU cells are related to their synaptic domain, whereas those to GABAergic cells are unrelated to the location of cell bodies and thus always similar (Chen et al 2018). These results suggest that differences in the dendritic arborization and organization of presynaptic inputs underlie the different patterns of clustering for sound information between GLU and GABAergic neurons.…”

“…The dendritic shapes and distributions of putative presynaptic inputs were different in the different cell types (Figs 3-5), suggesting that the composition of extrinsic input sources is different between cell types. A recent study has shown that GLU cells in different IC domains receive different combinations of extrinsic inputs, whereas GABAergic cells always receive a similar combination of extrinsic inputs (Chen et al 2018). It has also been reported that some characteristics of sound besides characteristic frequency are coded in spatially organized ways inside the ICC (Schreiner & Langner, 1997;Rees & Langner, 2005).…”