Abstract
In the auditory inferior colliculus (IC), serotonin reflects features of context including the valence of social interactions, stressful events, and prior social experience. However, within the dorsal raphe nucleus (DRN; B6 + B7), the source of serotonergic projections to the IC has not been resolved at the level of DRN subregions. Additionally, few studies have investigated which DRN subregions are engaged during naturalistic, sensory-driven social behaviors. We employ traditional, retrograde tract-tracing approaches to comprehensively map the topographic extent of DRN-IC projection neurons in male and female mice. We combine this approach with immediate early gene (cFos) mapping in order to describe the functional properties of DRN subregions during contexts in which serotonin fluctuates within the IC. These approaches provide novel evidence that the dorsal (DRd) and lateral (DRl) B7 subregions are primarily responsible for serotonergic innervation of the IC; further, we show that this projection is larger in male than in female mice. Additionally, DRd and the ventral B7 (DRv) contained more transcriptionally active serotonergic neurons irrespective of behavioral context. Male mice had more active serotonergic neurons in DRd and DRv than females following sociosexual encounters. However, serotonergic activity was correlated with the expression of female but not male social behaviors. The topographic organization of the DRN-IC projection provides the anatomical framework to test a mechanism underlying context-dependent auditory processing. We further highlight the importance of including sex as a biological variable when describing the functional topography of DRN.
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Acknowledgements
The authors wish to thank Dr. Jim Powers and the Indiana University Light Microscopy Imaging Center for technical assistance, Dr. Kelly Ronald for statistical advice, members of the Hurley Lab, and two anonymous reviewers whose comments improved this manuscript. This work was supported in part by funding from the National Institute of Health Common Themes in Reproductive Diversity Training Grant (5T32HD049336-12; CLP), Center for the Integrative Study in Animal Behavior (CLP; AK) and Indiana University (LMH).
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While some of the experiments described in this manuscript were being performed, Christopher L. Petersen received funding in the form of stipend support from the National Institute of Health Common Themes in Reproductive Diversity Training Grant (5T32HD049336-12). Reagents used in this study were purchased with funds provided to Christopher L. Petersen and Alexander Koo from the Indiana University Center for the Integrative Study of Animal Behavior, and laboratory startup funds to Laura M. Hurley.
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Conceptualization: CLP, LMH; Investigation: CLP, AK; Formal analysis: CLP, AK, BP; Resources: CLP, AK, LMH; Wrote the manuscript: CLP; Supervised the project: LMH.
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Petersen, C.L., Koo, A., Patel, B. et al. Serotonergic innervation of the auditory midbrain: dorsal raphe subregions differentially project to the auditory midbrain in male and female mice. Brain Struct Funct 225, 1855–1871 (2020). https://doi.org/10.1007/s00429-020-02098-3
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DOI: https://doi.org/10.1007/s00429-020-02098-3