title: Projection-specific modulation of dopamine neuron synapses by aversive and rewarding stimuli.
abstract: Midbrain dopamine (DA) neurons are not homogeneous but differ in their molecular properties and responses to external stimuli. We examined whether the modulation of excitatory synapses on DA neurons by rewarding or aversive stimuli depends on the brain area to which these DA neurons project. We identified DA neuron subpopulations in slices after injection of "Retrobeads" into single target areas of adult mice and found differences in basal synaptic properties. Administration of cocaine selectively modified excitatory synapses on DA cells projecting to nucleus accumbens (NAc) medial shell while an aversive stimulus selectively modified synapses on DA cells projecting to medial prefrontal cortex. In contrast, synapses on DA neurons projecting to NAc lateral shell were modified by both rewarding and aversive stimuli, which presumably reflects saliency. These results suggest that the mesocorticolimbic DA system may be comprised of three anatomically distinct circuits, each modified by distinct aspects of motivationally relevant stimuli.
authors.affiliation: Nancy Pritzker Laboratory, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Lokey Stem Cell Research Building, 265 Campus Drive, Room G1021, Stanford, CA 94305-5453, USA.
authors.forename: Stephan
authors.initials: S
authors.lastname: Lammel
authors.forename: Daniela I
authors.initials: DI
authors.lastname: Ion
authors.forename: Jochen
authors.initials: J
authors.lastname: Roeper
authors.forename: Robert C
authors.initials: RC
authors.lastname: Malenka
mesh_terms: D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D001710:Biotin / Q000031:analogs & derivatives / Q000378:metabolism; D002540:Cerebral Cortex / Q000502:physiology; D003042:Cocaine / Q000009:adverse effects; D004298:Dopamine / Q000378:metabolism*; D018765:Dopamine Uptake Inhibitors / Q000009:adverse effects; D004334:Drug Administration Schedule; D004558:Electric Stimulation; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D058787:GABA-A Receptor Antagonists / Q000494:pharmacology; D049452:Green Fluorescent Proteins / Q000235:genetics; D066298:In Vitro Techniques; D053444:Inhibitory Postsynaptic Potentials / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D008297:Male; D008636:Mesencephalon / Q000166:cytology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009434:Neural Pathways / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D018408:Patch-Clamp Techniques; D012201:Reward; D013378:Substantia Nigra / Q000502:physiology; D013569:Synapses / Q000235:genetics / Q000502:physiology*; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics / Q000378:metabolism
chemical_list: D018765:Dopamine Uptake Inhibitors; D018691:Excitatory Amino Acid Antagonists; D058787:GABA-A Receptor Antagonists; C070614:neurobiotin; D049452:Green Fluorescent Proteins; D001710:Biotin; D015763:2-Amino-5-phosphonovalerate; D014446:Tyrosine 3-Monooxygenase; D003042:Cocaine; D004298:Dopamine; D001640:Bicuculline