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

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.