title: Dopamine triggers heterosynaptic plasticity.
abstract: As a classic neuromodulator, dopamine has long been thought to modulate, rather than trigger, synaptic plasticity. In contrast, our present results demonstrate that within the parallel projections of dopaminergic and GABAergic terminals from the ventral tegmental area to the nucleus accumbens core (NAcCo), action-potential-activated release of dopamine heterosynaptically triggers LTD at GABAergic synapses, which is likely mediated by activating presynaptically located dopamine D1 class receptors and expressed by inhibiting presynaptic release of GABA. Moreover, this dopamine-mediated heterosynaptic LTD is abolished after withdrawal from cocaine exposure. These results suggest that action-potential-dependent dopamine release triggers very different cellular consequences from those induced by volume release or pharmacological manipulation. Activation of the ventral tegmental area to NAcCo projections is essential for emotional and motivational responses. This dopamine-mediated LTD allows a flexible output of NAcCo neurons, whereas disruption of this LTD may contribute to the rigid emotional and motivational state observed in addicts during cocaine withdrawal.
authors.affiliation: Department of Neuroscience, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA.
authors.forename: Masago
authors.initials: M
authors.lastname: Ishikawa
authors.forename: Mami
authors.initials: M
authors.lastname: Otaka
authors.forename: Yanhua H
authors.initials: YH
authors.lastname: Huang
authors.forename: Peter A
authors.initials: PA
authors.lastname: Neumann
authors.forename: Bradley D
authors.initials: BD
authors.lastname: Winters
authors.forename: Anthony A
authors.initials: AA
authors.lastname: Grace
authors.forename: Oliver M
authors.initials: OM
authors.lastname: Schlüter
authors.forename: Yan
authors.initials: Y
authors.lastname: Dong
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001565:Benzoates / Q000494:pharmacology; D000075402:Channelrhodopsins; D003042:Cocaine / Q000008:administration & dosage; D004298:Dopamine / Q000378:metabolism*; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage; D004558:Electric Stimulation; D059330:GABAergic Neurons / Q000187:drug effects / Q000502:physiology*; D005822:Genetic Vectors / Q000502:physiology; D005998:Glycine / Q000031:analogs & derivatives / Q000494:pharmacology; D066298:In Vitro Techniques; D053444:Inhibitory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D036881:Long-Term Synaptic Depression / Q000187:drug effects / Q000502:physiology*; D008297:Male; D009714:Nucleus Accumbens / Q000166:cytology; D062308:Optogenetics; D010721:Phosphinic Acids / Q000494:pharmacology; D010775:Photic Stimulation; D011412:Propanolamines / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013569:Synapses / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors; D014161:Transduction, Genetic; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D017557:Ventral Tegmental Area / Q000166:cytology
chemical_list: D001565:Benzoates; D000075402:Channelrhodopsins; D018765:Dopamine Uptake Inhibitors; D010721:Phosphinic Acids; D011412:Propanolamines; D011725:Pyridines; D011810:Quinoxalines; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline; C079694:alpha-methyl-4-carboxyphenylglycine; C085075:CGP 55845A; C121465:6-methyl-2-(phenylethynyl)pyridine; D014446:Tyrosine 3-Monooxygenase; D003042:Cocaine; D005998:Glycine; D004298:Dopamine