ELSC Seminar: Prof. Randy Blakely - October 16th, 2018 at 13:00

October 16, 2018

ELSC cordially invites you to the lecture given by:


Prof. Randy Blakely

Florida Atlantic University Brain Institute 


On the topic of:


“Presynaptic Autoreceptor Regulation of Dopamine Inactivation – Circuit Dependence and Disease Relevance”



The lecture will be held on Tuesday, October 16th, at 13:00

at ELSC: Becker Auditorium, Goodman Brain Sciences Bldg., 

 Edmond J. Safra Campus 


Light refreshments at 12:45




Presynaptic dopamine (DA) transporters (DATs) provide for efficient clearance of DA released by vesicular fusion. Drugs of abuse, such as cocaine and methamphetamine, target DAT and disrupt normal synaptic DA homeostasis. Drugs that target DAT are also used as medications for the treatment of Attention-Deficit Hyperactivity Disorder (ADHD). In a search for genetic contributors to ADHD, we identified multiple, rare coding variants that impact the function and regulation of DAT. One variant, DAT Val559, also identified in subjects with autism and bipolar disorder, leads to a state of spontaneous DA efflux, elevating extracellular DA through non-vesicular mechanisms. In DAT Val559 KI mice, we established that one consequence of tonic elevations in extracellular DA produced  by DAT Val559 is constitutive activation of presynaptic D2 autoreceptors (D2ARS). D2AR activation in the dorsal striatum, leads to DAT phosphorylation and elevated trafficking of transporters to the synaptic membrane, further amplifying non-vesicular DA release. In the ventral striatum, however, D2ARs do not regulate DAT, and as a consequence, the modest, spontaneous efflux of DA generated by DAT fails to self-reinforce, biasing consequences of the mutation to behaviors dependent on dorsal striatal function. Further analysis indicates that D2AR-DAT coupling is also sex dependent, with males with Val559 type functional disruptions likely to demonstrate impulsivity and reward-seeking based hypermotivation whereas females may display alterations in reward-sensing and valuation. Together, these findings point to a need to fully elaborate the broader, molecular and circuit-level variation that support changes in neurotransmitter signaling when modeling brain disease-associated gene mutations.