PT  - JOURNAL ARTICLE
AU  - Aishwarya S. Kulkarni
AU  - Maria del Mar Cortijo
AU  - Elizabeth R. Roberts
AU  - Tamara L. Suggs
AU  - Heather B. Stover
AU  - José I. Pena-Bravo
AU  - Jennifer A. Steiner
AU  - Kelvin C. Luk
AU  - Patrik Brundin
AU  - Daniel W. Wesson
TI  - Perturbation of <em>in vivo</em> neural activity following α-Synuclein seeding in the olfactory bulb
AID  - 10.1101/2020.04.17.045013
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.04.17.045013
4099  - http://biorxiv.org/content/early/2020/07/15/2020.04.17.045013.short
4100  - http://biorxiv.org/content/early/2020/07/15/2020.04.17.045013.full
AB  - 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.CONCLUSIONS Together, this work provides evidence that synucleinopathy impacts in vivo neural activity in the olfactory system at the network-level.Competing Interest StatementPatrik Brundin has received commercial support as a consultant from Axial Biotherapeutics, CuraSen, Fujifilm-Cellular Dynamics International, Idorsia, IOS Press Partners, LifeSci Capital LLC, Lundbeck A/S and Living Cell Technologies LTD. He has received commercial support for grants/research from Lundbeck A/S and Roche. He has ownership interests in Acousort AB and Axial Biotherapeutics and is on the steering committee of the NILO-PD trial. The authors declare no additional competing financial interests.