In synucleinopathies, α-synuclein (α-syn) is thought to exist within a dynamic equilibrium, comprising both α-syn oligomers (OSyn) and more aggregated forms. OSyn has been associated to neurodegeneration, neurotoxicity, and proinflammatory responses, even at low concentrations and is thought to be involved in Parkinson’s disease (PD) pathogenesis.To date, it is not clear whether the neurotoxicity exerted by α-syn aggregates is due to the presence of scattered oligomeric species, anticipating the formation of proper fibrillary α-syn, or whether it is sustained by α-syn species that are already in balance with more aggregated α-syn seedings.To define the events occurring during the initial stages of α-syn spreading, as well as to assess the in vivo relevance of OSyn for the development of motor and non-motor symptoms, we performed electrophysiological and behavioral tests in a rat model of synucleinopathy obtained by intrastriatal injection of OSyn, envisioning a scenario that precedes the formation of fibrillary α-syn aggregates.OSyn rats were found to display early abnormalities of motor activity and increased anxiety-like behavior, together with bidirectional impairment of striatal long-term synaptic plasticity. Novel pharmacological strategies will be evaluated to reverse these changes.Overall, this research will help further elucidate the events in the earliest stages of PD and the pathophysiological phenomena that lead to the onset of early non-motor symptoms. Moreover, our work will unravel more the initial mechanisms underlying the synaptic dysfunction produced by the oligomeric form of α-syn that accumulates in the striatum.