Perturbation of in vivo Neural Activity Following α-Synuclein Seeding in the Olfactory Bulb

Article type: Research Article

Authors: Kulkarni, Aishwarya S.^a | del Mar Cortijo, Maria^a | Roberts, Elizabeth R.^a | Suggs, Tamara L.^a | Stover, Heather B.^a | Pena-Bravo, José I.^a | Steiner, Jennifer A.^b | Luk, Kelvin C.^c | Brundin, Patrik^b | Wesson, Daniel W.^{a; *}

Affiliations: [a] Department of Pharmacology & Therapeutics, University of Florida, Gainesville, FL, USA | [b] Center for Neurodegenerative Science, Van Andel Institute, Grand Rapids, MI, USA | [c] Department of Pathology and Laboratory Medicine, Center for Neurodegenerative Disease Research and Institute on Aging, University of Pennsylvania School of Medicine, Philadelphia, PA, USA

Correspondence: [*] Correspondence to: Daniel W. Wesson, Department of Pharmacology & Therapeutics, University of Florida, 1200 Newell Drive, Gainesville, FL 32610, USA. [email protected]

Abstract: Background:Parkinson’s disease (PD) neuropathology is characterized by intraneuronal protein aggregates composed of misfolded α-Synuclein (α-Syn), as well as degeneration of substantia nigra dopamine neurons. Deficits in olfactory perception and aggregation of α-Syn in the olfactory bulb (OB) are observed during early stages of PD, and have been associated with the PD prodrome, before onset of the classic motor deficits. α-Syn fibrils injected into the OB of mice cause progressive propagation of α-Syn pathology throughout the olfactory system and are coupled to olfactory perceptual deficits. Objective:We hypothesized that accumulation of pathogenic α-Syn in the OB impairs neural activity in the olfactory system. Methods:To address this, we monitored spontaneous and odor-evoked local field potential dynamics in awake wild type mice simultaneously in the OB and piriform cortex (PCX) one, two, and three months following injection of pathogenic preformed α-Syn fibrils in the OB. Results:We detected α-Syn pathology in both the OB and PCX. We also observed that α-Syn fibril injections influenced odor-evoked activity in the OB. In particular, α-Syn fibril-injected mice displayed aberrantly high odor-evoked power in the beta spectral range. A similar change in activity was not detected in the PCX, despite high levels of α-Syn pathology. Conclusion:Together, this work provides evidence that synucleinopathy impacts in vivo neural activity in the olfactory system at the network-level.

Keywords: Parkinson’s disease, dementia, olfaction, synucleinopathy, Lewy pathology, piriform cortex, olfactory bulb, local field potential

DOI: 10.3233/JPD-202241

Journal: Journal of Parkinson's Disease, vol. Pre-press, no. Pre-press, pp. 1-17, 2020