title: Optogenetic versus electrical stimulation of dopamine terminals in the nucleus accumbens reveals local modulation of presynaptic release.
abstract: The nucleus accumbens is highly heterogeneous, integrating regionally distinct afferent projections and accumbal interneurons, resulting in diverse local microenvironments. Dopamine (DA) neuron terminals similarly express a heterogeneous collection of terminal receptors that modulate DA signaling. Cyclic voltammetry is often used to probe DA terminal dynamics in brain slice preparations; however, this method traditionally requires electrical stimulation to induce DA release. Electrical stimulation excites all of the neuronal processes in the stimulation field, potentially introducing simultaneous, multi-synaptic modulation of DA terminal release. We used optogenetics to selectively stimulate DA terminals and used voltammetry to compare DA responses from electrical and optical stimulation of the same area of tissue around a recording electrode. We found that with multiple pulse stimulation trains, optically stimulated DA release increasingly exceeded that of electrical stimulation. Furthermore, electrical stimulation produced inhibition of DA release across longer duration stimulations. The GABAB antagonist, CGP 55845, increased electrically stimulated DA release significantly more than light stimulated release. The nicotinic acetylcholine receptor antagonist, dihydro-β-erythroidine hydrobromide, inhibited single pulse electrically stimulated DA release while having no effect on optically stimulated DA release. Our results demonstrate that electrical stimulation introduces local multi-synaptic modulation of DA release that is absent with optogenetically targeted stimulation.
authors.affiliation: Department of Physiology and Pharmacology, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA.
authors.forename: James R
authors.initials: JR
authors.lastname: Melchior
authors.affiliation: Department of Physiology and Pharmacology, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Ferris
authors.affiliation: Departments of Psychiatry and Cell Biology and Physiology, University of North Carolina, Chapel Hill, North Carolina, USA.
authors.forename: Garret D
authors.initials: GD
authors.lastname: Stuber
authors.affiliation: Department of Biological Sciences, Western Michigan University School of Medicine, Kalamazoo, Michigan, USA.
authors.forename: David R
authors.initials: DR
authors.lastname: Riddle
authors.affiliation: Department of Physiology and Pharmacology, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA.
authors.forename: Sara R
authors.initials: SR
authors.lastname: Jones
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D016477:Artifacts; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000235:genetics; D000075402:Channelrhodopsins; D059329:Cholinergic Neurons / Q000187:drug effects / Q000502:physiology; D004298:Dopamine / Q000378:metabolism*; D059290:Dopaminergic Neurons / Q000187:drug effects / Q000378:metabolism*; D004558:Electric Stimulation; D058788:GABA-B Receptor Antagonists / Q000494:pharmacology; D059330:GABAergic Neurons / Q000187:drug effects / Q000502:physiology; D055879:Gene Knock-In Techniques; D007395:Interneurons / Q000187:drug effects / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008839:Microelectrodes; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics; D009714:Nucleus Accumbens / Q000166:cytology* / Q000378:metabolism; D062308:Optogenetics; D010721:Phosphinic Acids / Q000494:pharmacology; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011412:Propanolamines / Q000494:pharmacology; D013569:Synapses / Q000187:drug effects / Q000502:physiology; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics; D017557:Ventral Tegmental Area / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000502:physiology
chemical_list: D000075402:Channelrhodopsins; D058788:GABA-B Receptor Antagonists; D009419:Nerve Tissue Proteins; D010721:Phosphinic Acids; D011412:Propanolamines; C085075:CGP 55845A; D005680:gamma-Aminobutyric Acid; D014446:Tyrosine 3-Monooxygenase; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D000109:Acetylcholine; D004298:Dopamine
keywords: GABA; acetylcholine; dopamine; nucleus accumbens; optogenetics; voltammetry