Mejaes, Jennifer Ilham. The effect of the synaptojanin1 gene mutation on reward processing & motivational behavior. Retrieved from https://doi.org/doi:10.7282/t3-6te7-7847
DescriptionThe synaptojanin1 (SYNJ1) gene is known to be important for dopamine-related disorders, and mutations of the SYNJ1 gene have been linked to bipolar disorder, schizophrenia, and parkinsonism (Quadri. M et al., 2013; Taghavi et al., 2018; Saito et al., 2001). Recent evidence has demonstrated that Synj1 deficient mice (Synj1+/-) have impairments in their dopaminergic system as well as synaptic recycling (Pan et al., 2020; Cremona et al., 1999). These slower rates of vesicle recycling are hypothesized to be due to deficits in the Synj1 gene which result in abnormal activation of the mTOR signaling pathway (Aki et al., 2020). Despite these clear links to midbrain dopamine systems, the effect of Synj1 mutations on motivation and drug-seeking behaviors has not been examined. To assess the role of the Synj1 gene in motivation, we subjected male and female Synj1+/- and their littermate controls (Synj1+/+) to a battery of behavioral tests used to assess specific features of motivated behavior. These tests included the elevated plus maze, open field assay, sucrose preference test, operant conditioning paradigm and progressive ratio-schedule task, a cocaine conditioned place preference paradigm that included a drug primed reinstatement test and finally an object location memory task. Our results indicate that Synj1+/- mice exhibit normal anxiety, locomotor behaviors and hedonic responses to sucrose. Additionally, Synj1+/- mice were also found to show no differences in operant learning or effortful responding for sucrose compared to their Synj1+/+ counterparts. Moreover, male Synj1+/- mice specifically, were found to show a weak place preference score for cocaine, which could not be attributed to deficits in spatial memory, which suggests that this weak cocaine place preference score is due to changes in the value of cocaine. Finally, we inferred from the western blot data that a Synj1 deficiency may heighten baseline levels of mTOR in the midbrain and striatum, preventing further cocaine-induced phosphorylated mTOR plasticity.