α-Synuclein perturbs in vivo neural activity following seeding in the olfactory bulb

Kulkarni, A. S.; Cortijo, M. d. M.; Roberts, E. R.; Suggs, T. L.; Stover, H. B.; Pena-Bravo, J. I.; Steiner, J. A.; Luk, K. C.; Brundin, P.; Wesson, D. W.

doi:10.1101/2020.04.17.045013

bioRxiv · 10.1101/2020.04.17.045013

α-Synuclein perturbs in vivo neural activity following seeding in the olfactory bulb

Kulkarni, A. S.·Cortijo, M. d. M.·Roberts, E. R.·Suggs, T. L.·Stover, H. B.·Pena-Bravo, J. I.·Steiner, J. A.·Luk, K. C.·Brundin, P.·Wesson, D. W.

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Abstract

BACKGROUNDParkinsons disease (PD) neuropathology is characterized by intraneuronal protein aggregates composed of misfolded -Synuclein (-Syn), as well as degeneration of substantia nigra dopamine neurons. Deficits in olfactory perception and aggregation of -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. -Syn fibrils injected into the OB of mice cause progressive propagation of -Syn pathology throughout the olfactory system and are coupled to olfactory perceptual deficits. OBJECTIVEWe hypothesized that accumulation of pathogenic -Syn in the OB impairs neural activity in the olfactory system. METHODSTo 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 -Syn fibrils in the OB. RESULTSWe detected -Syn pathology in both the OB and PCX. We also observed that -Syn fibril injections influenced odor-evoked activity in the OB. In particular, -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 -Syn pathology. CONCLUSIONSTogether, this work provides evidence that synucleinopathy impacts in vivo neural activity in the olfactory system at the network-level.

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Kulkarni, A. S., Cortijo, M. d. M., Roberts, E. R., Suggs, T. L., Stover, H. B., Pena-Bravo, J. I., Steiner, J. A., Luk, K. C., Brundin, P., Wesson, D. W.. 2020-04-18. α-Synuclein perturbs in vivo neural activity following seeding in the olfactory bulb. https://doi.org/10.1101/2020.04.17.045013

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