Behavioral consequences of point mutations in the vesicular acetylcholine transporter
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Abstract
The neurotransmitter acetylcholine (ACh) is involved in critical organismal functions as locomotion, learning and memory. Therefore, alterations in this neurotransmitter system is a key underlying factor in movement and cognitive deficits. The vesicular acetylcholine transporter (VAChT) mediates the packaging of ACh into synaptic vesicles for exocytotic release. Mutations in this protein ultimately diminish locomotion whereas complete loss of function of VAChT is fatal. The direct role of altered acetylcholine release and its association with impairment or enhancement of cognitive functions is still not fully understood. We hypothesize that point mutations in VAChT causes age-related deficits in cholinergic-mediated behaviors such as locomotion, learning and memory. Using Drosophila melanogaster as a model system, we have generated several mutations within VAChT and observed its effect on survivability, longevity and locomotive behavior. Here we report that VAChT point mutants causes defects in locomotion ability and an allele dependent deficit in lifespan. These results demonstrate that cholinergic release is important for the regulation of behavioral performance in Drosophila. In future studies, we will test methodologies to effectively rescue these deficits with implications for intervention strategies to treat cholinergic deprived disorders such as Alzheimer’s disease. Future studies will turn to investigating the effects of VAChT overexpression to determine whether the deficits seen in the Vacht mutants can be decreased or reversed.