Astrocyte-Regulated ATP Signaling on Motivational Behavior in Mice
Student Presenter(s): Aarya Nehe
Faculty Mentor: Weikang Cai
Department: Biomedical Sciences
School/College: College of Arts and Sciences, Long Island
Dopamine neurons are located in the substantia nigra, ventral tegmental area, and hypothalamus of the brain. They release dopamine at specific brain regions to regulate motivational pathways. It has been demonstrated that elevated dopamine levels further increase motivation in mice to obtain a food reward. Conversely, decreasing the amount of dopamine signaling results in depressive-like behavior. Astrocytes release ATP through exocytosis to modulate neuronal activity. This mechanism occurs via the vesicular nucleotide transporter gene VNUT to provide a mechanism for the storage and release of ATP. In the present study, in order to further investigate the role of dopaminergic activity, we generated a novel transgenic mouse model in which VNUT is silenced in astrocytes. The motivation of both sexes of mice with knockout of the VNUT gene (VNUTKO) was compared against wild-type (WT) mice using sucrose pellets. The mice were habituated to a feeding experiment device (FED) that dispensed the pellets after burrowing their nose into a cavity to trigger a sensor in the FED. The progressively more effort settings would challenge the mice to trigger the sensor multiple times to dispense a sugar tablet, thus testing their motivation for obtaining a food reward. The results suggested that in male mice, VNUTKO alone produced a significant decrease in motivation versus WT. Future studies can explore if a decrease in the exocytosis mechanism of ATP alone can decrease dopamine signaling.