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Loss of Kirrel family members alters glomerular structure and synapse numbers in the accessory olfactory bulb

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Abstract

The accessory olfactory system controls social and sexual behaviours in mice, both of which are critical for their survival. Vomeronasal sensory neuron (VSN) axons form synapses with mitral cell dendrites in glomeruli of the accessory olfactory bulb (AOB). Axons of VSNs expressing the same vomeronasal receptor (VR) converge into multiple glomeruli within spatially conserved regions of the AOB. Here, we have examined the role of the cell adhesion molecule Kirrel2 in the formation of glomeruli within the AOB. We find that Kirrel2 expression is dispensable for early axonal guidance events, such as fasciculation of the vomeronasal tract and segregation of apical and basal VSN axons into the anterior and posterior regions of the AOB, but is necessary for glomeruli formation. Specific ablation of Kirrel2 expression in VSN axons results in the disorganization of the glomerular layer of the posterior AOB and in the formation of fewer and larger glomeruli. Furthermore, simultaneous ablation of Kirrel2 and Kirrel3 expression leads to a loss of morphologically identifiable glomeruli in the AOB, reduced excitatory synapse numbers, and larger presynaptic terminals. Taken together, our results demonstrate that Kirrel2 and Kirrel3 are essential for the formation of glomeruli and suggest they contribute to synaptogenesis in the AOB.

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Acknowledgements

We thank members of the Cloutier lab for helpful discussion and technical advice. We thank Drs. Louis Hermo and Thomas Stroh, as well as the Facility for Electron Microscopy Research of McGill University for invaluable help and advice with synapse analyses. We thank Dr. David Ginty for Kirrel cDNAs and Mitra Cowan for the generation of Kirrel2 mouse models. This work was supported by the Canadian Institutes for Health Research and the Natural Sciences and Engineering Council of Canada (J.-F. C.). A. C. B held a studentship from the Natural Sciences and Engineering Council of Canada. J. E. A. Prince held studentships from the Fonds Québécois pour la Recherche sur la Nature et les Technologies and the Faculty of Medicine at McGill University. Reesha Raja is a recipient of a Vanier Scholarship from the Canadian Institutes of Health Research. J.-F. C. is a FRQS Chercheur Sénior.

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Authors and Affiliations

  1. Montreal Neurological Institute, 3801 University, Montréal, QC, H3A 2B4, Canada

    Alexandra C. Brignall, Reesha Raja, Janet E. A. Prince, Emilie Dumontier & Jean-François Cloutier

  2. Department of Neurology and Neurosurgery, McGill University, Montréal, Canada

    Reesha Raja, Janet E. A. Prince & Jean-François Cloutier

  3. Department of Anatomy and Cell Biology, McGill University, Montréal, Canada

    Alexandra C. Brignall, Alina Phen & Jean-François Cloutier

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  1. Alexandra C. Brignall
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  2. Reesha Raja
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Correspondence to Jean-François Cloutier.

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Brignall, A.C., Raja, R., Phen, A. et al. Loss of Kirrel family members alters glomerular structure and synapse numbers in the accessory olfactory bulb. Brain Struct Funct 223, 307–319 (2018). https://doi.org/10.1007/s00429-017-1485-0

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  • DOI: https://doi.org/10.1007/s00429-017-1485-0

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