Cross-hemispheric dopamine projections have functional significance.
Dopamine signaling occurs on a subsecond timescale, and its dysregulation is implicated in pathologies ranging from drug addiction to Parkinson's disease. Anatomic evidence suggests that some dopamine neurons have cross-hemispheric projections, but the significance of these projections is unknown. Here we report unprecedented interhemispheric communication in the midbrain dopamine system of awake and anesthetized rats. In the anesthetized rats, optogenetic and electrical stimulation of dopamine cells elicited physiologically relevant dopamine release in the contralateral striatum. Contralateral release differed between the dorsal and ventral striatum owing to differential regulation by D2-like receptors. In the freely moving animals, simultaneous bilateral measurements revealed that dopamine release synchronizes between hemispheres and intact, contralateral projections can release dopamine in the midbrain of 6-hydroxydopamine-lesioned rats. These experiments are the first, to our knowledge, to show cross-hemispheric synchronicity in dopamine signaling and support a functional role for contralateral projections. In addition, our data reveal that psychostimulants, such as amphetamine, promote the coupling of dopamine transients between hemispheres.
Department of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599; UNC Neuroscience Center, UNC School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599;
Megan E
ME
Fox
Institute of Translational Biomedicine, St. Petersburg State University, St. Petersburg 199034, Russia;
Maria A
MA
Mikhailova
Department of Pharmacology and Toxicology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, NY 14260;
Caroline E
CE
Bass
Department of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599; UNC Neuroscience Center, UNC School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599;
Pavel
P
Takmakov
Institute of Translational Biomedicine, St. Petersburg State University, St. Petersburg 199034, Russia;
Raul R
RR
Gainetdinov
Institute of Translational Biomedicine, St. Petersburg State University, St. Petersburg 199034, Russia; Department of Neurobiology and Anatomy, Wake Forest School of Medicine, Winston Salem, NC 27157.
Evgeny A
EA
Budygin
Department of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599; UNC Neuroscience Center, UNC School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599; rmw@unc.edu.
R Mark
RM
Wightman
D000818:Animals; D054022:Cerebrum / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D008297:Male; D009714:Nucleus Accumbens / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D004298:Dopamine
dopamine; dorsal striatum; nucleus accumbens; synchrony; voltammetry