Distinct roles of synaptic transmission in direct and indirect striatal pathways to reward and aversive behavior.
In the basal ganglia, convergent input and dopaminergic modulation of the direct striatonigral and the indirect striatopallidal pathways are critical in rewarding and aversive learning and drug addiction. To explore how the basal ganglia information is processed and integrated through these two pathways, we developed a reversible neurotransmission blocking technique, in which transmission of each pathway was selectively blocked by specific expression of transmission-blocking tetanus toxin in a doxycycline-dependent manner. The results indicated that the coordinated modulation of these two pathways was necessary for dopamine-mediated acute psychostimulant actions. This modulation, however, shifted to the predominant roles of the direct pathway in reward learning and cocaine sensitization and the indirect pathway in aversive behavior. These two pathways thus have distinct roles: the direct pathway critical for distinguishing associative rewarding stimuli from nonassociative ones and the indirect pathway for rapid memory formation to avoid aversive stimuli.
Hikida
Takatoshi
T
Department of Systems Biology, Osaka Bioscience Institute, 6-2-4 Furuedai, Suita, Osaka 565-0874, Japan.
Kimura
Kensuke
K
Wada
Norio
N
Funabiki
Kazuo
K
Nakanishi
Shigetada
S
D000200:Action Potentials / Q000187:drug effects; D000222:Adaptation, Physiological / Q000187:drug effects / Q000235:genetics; D000704:Analysis of Variance; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects / Q000502:physiology*; D001522:Behavior, Animal; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D002772:Cholera Toxin / Q000378:metabolism; D003042:Cocaine / Q000494:pharmacology; D003216:Conditioning, Operant / Q000187:drug effects; D003342:Corpus Striatum / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D000229:Dependovirus / Q000502:physiology; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D004318:Doxycycline / Q000008:administration & dosage / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005786:Gene Expression Regulation / Q000187:drug effects; D008694:Methamphetamine / Q000494:pharmacology; D051379:Mice; D008822:Mice, Transgenic; D009434:Neural Pathways / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D009498:Neurotoxins; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics; D012201:Reward; D013378:Substantia Nigra / Q000166:cytology; D009435:Synaptic Transmission / Q000502:physiology*; D013744:Tetanus Toxin; D014162:Transfection / Q000379:methods; D050988:Vesicle-Associated Membrane Protein 2 / Q000235:genetics / Q000378:metabolism
D000697:Central Nervous System Stimulants; D018765:Dopamine Uptake Inhibitors; D009498:Neurotoxins; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; C508139:TNTCFP protein; D013744:Tetanus Toxin; D050988:Vesicle-Associated Membrane Protein 2; C494808:vesicle-associated membrane protein 2, mouse; D008694:Methamphetamine; D002772:Cholera Toxin; D003042:Cocaine; D004318:Doxycycline