Midbrain DA neurons project to the striatum where released DA contributes to the regulation of movement, motor learning, motivation, and reward. Motor deficits in Parkinson’s disease result from progressive nigrostriatal DA neuron degeneration. We have shown that voluntary exercise boosts striatal DA release by up to 50%, although DA tissue content is unchanged. Previous studies in control mice have shown that only 30% of DA varicosities release transmitter. Consistent with this, only 30% of DA varicosities express bassoon, a crucial presynaptic scaffolding protein that facilitates the tethering and reloading of synaptic vesicles. We hypothesize that exercise-enhanced DA release is attributable to an increase in the number of active DA release sites, indicated by immunostaining for bassoon. 

Exercising mice (runners) were housed individually with running wheels for 30 days, whereas controls were housed with locked wheels. Immunohistochemistry was performed on free-floating, 50-μm sagittal striatal sections using rabbit anti-tyrosine hydroxylase (TH) antibody to label DA axons and a guinea pig anti-bassoon antibody. Fluorescently tagged secondaries were anti-rabbit Cy3 and anti-guinea pig Alexa 488. Images were acquired with an Andor BC43 confocal microscope and processed using Imaris software.

We have optimized staining parameters and have identified bassoon puncta in TH-positive axons. We are currently developing methods to quantify the density of bassoon-immunoreactive puncta in DA axons to assess possible differences between runners and controls.  

We hypothesize that aerobic exercise induces a significant increase in bassoon-positive puncta, given the robust increase in evoked DA that we see in runners vs. controls. If verified, our findings will provide new insight into the beneficial aspects of exercise in Parkinson’s patients.