Brain-wide sensory aberrations in a Parkinson's Disease mouse model revealed by functional MRI

Abstract

Parkinsons disease (PD) is associated with irreparable damage to dopaminergic neurons in brain areas involved in movement. Frequently, a very early symptom of PD involves an impaired sense of smell, while other studies suggest a broader impairment of other sensory modalities. Still, the associated brain-wide mechanisms underlying this phenomenon remain unclear. Here, we harness in vivo functional Magnetic Resonance Imaging (fMRI) at 9.4T to investigate how the olfactory and visual systems are affected in an -Synuclein (Syn) mouse model of PD. We find significant aberrations in fMRI responses along both sensory pathways including decreases in activation extent and in activation amplitude. Deficits in the olfactory system were larger than in the visual pathway, but nevertheless both sensory systems were clearly impacted, suggesting a more overarching mechanism may be involved. To further ensure that the aberrations observed in the fMRI signals were not driven solely by putative vascular deficiency, we quantified c-FOS expression in the olfactory system and found statistically significant decreases in the PD group when compared to age-matched controls. Hence, our findings indicate a neural origin for the observed fMRI aberrations. Our findings thus demonstrate a more global deficiency in sensory systems in the (Syn) mouse model. One Sentence SummaryParkinsons disease (PD) is associated with an impaired sense of smell and more generally sensory deficits, but the associated brain-wide mechanisms remain unclear; here, we investigate aberrations in BOLD-fMRI responses along sensory pathways in an SYN PD mouse model.