title: Dopaminergic and glutamatergic microdomains in a subset of rodent mesoaccumbens axons.
abstract: Mesoaccumbens fibers are thought to co-release dopamine and glutamate. However, the mechanism is unclear, and co-release by mesoaccumbens fibers has not been documented. Using electron microcopy, we found that some mesoaccumbens fibers have vesicular transporters for dopamine (VMAT2) in axon segments that are continuous with axon terminals that lack VMAT2, but contain vesicular glutamate transporters type 2 (VGluT2). In vivo overexpression of VMAT2 did not change the segregation of the two vesicular types, suggesting the existence of highly regulated mechanisms for maintaining this segregation. The mesoaccumbens axon terminals containing VGluT2 vesicles make asymmetric synapses, commonly associated with excitatory signaling. Using optogenetics, we found that dopamine and glutamate were released from the same mesoaccumbens fibers. These findings reveal a complex type of signaling by mesoaccumbens fibers in which dopamine and glutamate can be released from the same axons, but are not normally released at the same site or from the same synaptic vesicles.
authors: National Institute on Drug Abuse, Neuronal Networks Section, US National Institutes of Health, Baltimore, Maryland, USA.
authors: Shiliang
authors: S
authors: Zhang
authors: National Institute on Drug Abuse, Neuronal Networks Section, US National Institutes of Health, Baltimore, Maryland, USA.
authors: Jia
authors: J
authors: Qi
authors: National Institute on Drug Abuse, Neuronal Networks Section, US National Institutes of Health, Baltimore, Maryland, USA.
authors: Xueping
authors: X
authors: Li
authors: National Institute on Drug Abuse, Neuronal Networks Section, US National Institutes of Health, Baltimore, Maryland, USA.
authors: Hui-Ling
authors: HL
authors: Wang
authors: National Institute on Drug Abuse, Synaptic Plasticity Section, US National Institutes of Health, Baltimore, Maryland, USA.
authors: Jonathan P
authors: 0000000330449565
authors: JP
authors: Britt
authors: National Institute on Drug Abuse, Electrophysiology Research Section, US National Institutes of Health, Baltimore, Maryland, USA.
authors: Alexander F
authors: AF
authors: Hoffman
authors: National Institute on Drug Abuse, Synaptic Plasticity Section, US National Institutes of Health, Baltimore, Maryland, USA.
authors: Antonello
authors: A
authors: Bonci
authors: National Institute on Drug Abuse, Electrophysiology Research Section, US National Institutes of Health, Baltimore, Maryland, USA.
authors: Carl R
authors: CR
authors: Lupica
authors: National Institute on Drug Abuse, Neuronal Networks Section, US National Institutes of Health, Baltimore, Maryland, USA.
authors: Marisela
authors: M
authors: Morales
mesh_terms: D000818:Animals; D001369:Axons / Q000502:physiology / Q000648:ultrastructure*; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000235:genetics / Q000378:metabolism; D000075402:Channelrhodopsins; D004298:Dopamine / Q000378:metabolism*; D018698:Glutamic Acid / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D021962:Membrane Microdomains / Q000378:metabolism* / Q000648:ultrastructure; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D009714:Nucleus Accumbens / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013572:Synaptic Vesicles / Q000378:metabolism / Q000648:ultrastructure; D014161:Transduction, Genetic; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics / Q000378:metabolism; D017557:Ventral Tegmental Area / Q000166:cytology*; D050599:Vesicular Glutamate Transport Protein 2 / Q000235:genetics / Q000378:metabolism
chemical_list: D000075402:Channelrhodopsins; D050599:Vesicular Glutamate Transport Protein 2; D018698:Glutamic Acid; D014446:Tyrosine 3-Monooxygenase; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; C517675:Camk2a protein, rat; D004298:Dopamine