Optogenetic versus electrical stimulation of dopamine terminals in the nucleus accumbens reveals local modulation of presynaptic release.

Melchior JR, Ferris MJ, Stuber GD, Riddle DR, Jones SR
J Neurochem. 2015 134 (5): 833-44

PMID: 26011081 · PMCID: PMC4537642 · DOI:10.1111/jnc.13177

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.

© 2015 International Society for Neurochemistry.

MeSH Terms (28)

Acetylcholine Animals Artifacts Calcium-Calmodulin-Dependent Protein Kinase Type 2 Channelrhodopsins Cholinergic Neurons Dopamine Dopaminergic Neurons Electric Stimulation GABA-B Receptor Antagonists GABAergic Neurons gamma-Aminobutyric Acid Gene Knock-In Techniques Interneurons Male Mice Mice, Inbred C57BL Microelectrodes Nerve Tissue Proteins Nucleus Accumbens Optogenetics Phosphinic Acids Presynaptic Terminals Promoter Regions, Genetic Propanolamines Synapses Tyrosine 3-Monooxygenase Ventral Tegmental Area

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