Assessing Cognitive Function in a Mouse Model of Synucleinopathy
Abstract
A common hallmark of neurodegenerative diseases is the formation and spreading of misfolded protein. In synucleinopathies, the aggregation-prone alpha-synuclein (α-syn) is the pivotal player. At present, whether cognitive deficits in synucleinopathies arise due to increased protein misfolding is unclear. We utilized the Bussey-Saksida touchscreen system to study the impact of α-syn pathology on cognition. M83 homozygous mice, a model of synucleinopathy, were impaired in reversal learning in the Pairwise Visual Discrimination (PVD) reversal task, but do not show attentional impairments in the 5-Choice Serial Reaction Time task. In contrast, M83 hemizygous mice do not show deficits in the PVD reversal task. Moreover, when α-syn pathology was accelerated using α-syn preformed fibrils in M83 hemizygous mice, impairments were induced early in the PVD reversal task in conjunction with wide distribution of α-syn aggregates in the brain. Together, our findings indicate that accumulation and spreading of α-syn triggers cognitive deficits in M83 mice, specifically in behavioural flexibility.