Olfactory information processing in a Parkinson’s disease mouse model

Abstract

Olfactory dysfunction is one of the earliest clinical symptoms of Parkinson’s disease (PD), preceding the onset of the motor deficits. PD occurs as a result of altered αsynuclein (α-syn) expression leading to its aggregation. α-syn is a natively unfolded protein found in various bodily tissues. In brain, it is predominantly found in the presynaptic terminals where they are involved in vesicular transport. α-syn aggregates can be found in Lewy bodies and Lewy neurites in neural tissues, which are a characteristic pathophysiological hallmarks of PD. In this project, we created a PD mouse model by injecting the abnormally aggregated forms of human wild type α-syn into the olfactory bulb of wild type mice. A series of olfactory behavioral assays were carried out to check for any sensory impairment. Their olfactory behavior was studied in detail by analyzing the detection and discrimination abilities of mice using a go/no-go operant conditioning paradigm. Mice injected with oligomeric and fibrillar forms of α-syn exhibited impaired learning and longer reaction times for the first complex odor pair discrimination that we performed. The learning improved when a subsequent odor discrimination task was done. However, they still showed the reaction time phenotype. We also investigated if our strategy led to the development of characteristic motor impairments or anxiety-like behaviors in our mouse model. As these mice did not exhibit any motor deficits, they offer as an ideal model to study the physiological basis of smell dysfunction observed in PD patients.