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Cholinergic Boutons are Distributed Along the Dendrites and Somata of VIP Neurons in the Inferior Colliculus

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Abstract

Cholinergic signaling shapes sound processing and plasticity in the inferior colliculus (IC), the midbrain hub of the central auditory system, but how cholinergic terminals contact and influence individual neuron types in the IC remains largely unknown. Using pharmacology and electrophysiology, we recently found that acetylcholine strongly excites VIP neurons, a class of glutamatergic principal neurons in the IC, by activating α3β4* nicotinic acetylcholine receptors (nAChRs). Here, we confirm and extend these results using tissue from mice of both sexes. First, we show that mRNA encoding α3 and β4 nAChR subunits is expressed in many neurons throughout the IC, including most VIP neurons, suggesting that these subunits, which are rare in the brain, are important mediators of cholinergic signaling in the IC. Next, by combining fluorescent labeling of VIP neurons and immunofluorescence against the vesicular acetylcholine transporter (VAChT), we show that individual VIP neurons in the central nucleus of the IC (ICc) are contacted by a large number of cholinergic boutons. Cholinergic boutons were distributed adjacent to the somata and along the full length of the dendritic arbors of VIP neurons, positioning cholinergic signaling to affect synaptic computations arising throughout the somatodendritic compartments of VIP neurons. In addition, cholinergic boutons were occasionally observed in close apposition to dendritic spines on VIP neurons, raising the possibility that cholinergic signaling also modulates presynaptic release onto VIP neurons. Together, these results strengthen the evidence that cholinergic signaling exerts widespread influence on auditory computations performed by VIP neurons and other neurons in the IC.

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All data will be made available upon reasonable request to the corresponding author.

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Acknowledgements

We thank Nichole Beebe, David Goyer, Jeffrey Mellott, William Noftz, and Brett Schofield for helpful advice and feedback, and Marina Silveira for help with the in situ hybridization experiments.

Funding

This work was supported by National Institutes of Health Grants F31 DC019292 (LMR-P) and R01 DC018284 (MTR).

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Authors and Affiliations

  1. Kresge Hearing Research Institute, Department of Otolaryngology – Head and Neck Surgery, University of Michigan, MI, Ann Arbor, 48109, USA

    Julia T. Kwapiszewski, Luis M. Rivera-Perez & Michael T. Roberts

  2. Department of Molecular and Integrative Pharmacology, University of Michigan, MI, Ann Arbor, 48109, USA

    Michael T. Roberts

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  1. Julia T. Kwapiszewski
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All authors conceived of the study, designed experiments, prepared figures, composed and revised the manuscript, and approved the submitted version. JTK and LMR-P performed experiments and analyzed data. MTR obtained funding and supervised the study.

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Correspondence to Michael T. Roberts.

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This article was first published as a preprint: Kwapiszewski JT, Rivera-Perez LM, and Roberts MT (2022). Cholinergic boutons are distributed along the dendrites and somata of VIP neurons in the inferior colliculus. bioRxiv. doi: https://doi.org/10.1101/2022.09.18.508423. 

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Kwapiszewski, J.T., Rivera-Perez, L.M. & Roberts, M.T. Cholinergic Boutons are Distributed Along the Dendrites and Somata of VIP Neurons in the Inferior Colliculus. JARO 24, 181–196 (2023). https://doi.org/10.1007/s10162-022-00885-9

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