Functional Reintegration of Sensory Neurons and Transitional Dendritic Reduction of Mitral/Tufted Cells during Injury-Induced Recovery of the Larval Xenopus Olfactory Circuit

Abstract

Understanding the mechanisms involved in maintaining lifelong neurogenesis has a clear biological and clinical interest. In the present study, we performed olfactory nerve transection on larval Xenopus to induce severe damage to the olfactory circuitry. We surveyed the timing of the degeneration, subsequent rewiring and functional regeneration of the olfactory system following injury. A range of structural labeling techniques and functional calcium imaging were performed on both tissue slices and whole brain preparations. Cell death of olfactory receptor neurons and proliferation of stem cells in the olfactory epithelium were immediately increased following lesion. New olfactory receptor neurons repopulated the olfactory epithelium and once again showed functional responses to natural odorants within 1 week after transection. Reinnervation of the olfactory bulb (OB) by newly formed olfactory receptor neuron axons also began at this time. Additionally, we observed a temporary increase in cell death in the OB and a subsequent loss in OB volume. Mitral/tufted cells, the second order neurons of the olfactory system, largely survived, but transiently lost dendritic tuft complexity. The first odorant-induced responses in the OB were observed 3 weeks after nerve transection and the olfactory network showed signs of major recovery, both structurally and functionally, after 7 weeks.

Structural and Functional Plasticity in the Regenerating Olfactory System of the Migratory Locust

“…Here, neurogenesis during development and a lifelong neuronal turnover in the olfactory epithelium are essential contributions to the regenerative capabilities of the olfactory circuitry. Transsection of the fully functional olfactory nerve of Xenopus larvae causes degeneration of ORN in the sensory epithelium which is followed by cell death in the postsynaptic olfactory bulb and reduction of its volume (Hawkins et al, 2017). The neural injury induces an increase in epithelial stem cell proliferation and newly formed ORN start to reinnervate the olfactory bulb within 1 week.…”

“…The neural injury induces an increase in epithelial stem cell proliferation and newly formed ORN start to reinnervate the olfactory bulb within 1 week. Olfactory network reconstruction, as assayed by cellular calcium imaging in the olfactory bulb, appears to recover within 7 weeks (Hawkins et al, 2017).…”

Principles of odor coding in vertebrates and artificial chemosensory systems

“…In contrast, neurons of the GG and the SO, the two other known olfactory subsystems, do not appear to house proliferative BCs (180,181). In nonmammalian vertebrates, areas with postembryonal neurogenesis are more widespread (182) and also include the OS (183)(184)(185)(186). Neuronal stem cells of the two central areas supply new interneurons to the hippocampus and the OB, respectively (179).…”

“…Neuronal stem cells, i.e., BCs (see sect. 5.1.2) in the epithelia of the main and accessory OS, generate new receptor neurons throughout the lifetime of an organism and contribute to the epithelial regenerative capacity (97,183,185,187).…”

Network formation and reorganization of the olfactory system of Xenopus laevis

“…mouse, Schwob et al, 1999;Schwob, 2002;St John and Key, 2003;McMillan Carr et al, 2004;Blanco-Hernández et al, 2012;Cheung et al, 2014;zebrafish, Godoy et al, 2020;Calvo-Ochoa et al, 2021). Xenopus laevis larvae in particular have been found to withstand a variety of lesions to the olfactory system and recover, at least to a certain degree (Kobayashi and Costanzo, 2009;Frontera et al, 2016;Hawkins et al, 2017). As the organization of the Xenopus olfactory system is similar to that of other vertebrates (Manzini et al, 2022), Xenopus larvae are thus a promising animal model in which to investigate the general principles of neural recovery after lesion.…”