title: Pathway-specific modulation of nucleus accumbens in reward and aversive behavior via selective transmitter receptors.
abstract: The basal ganglia-thalamocortical circuitry plays a central role in selecting actions that achieve reward-seeking outcomes and avoid aversive ones. Inputs of the nucleus accumbens (NAc) in this circuitry are transmitted through two parallel pathways: the striatonigral direct pathway and the striatopallidal indirect pathway. In the NAc, dopaminergic (DA) modulation of the direct and the indirect pathways is critical in reward-based and aversive learning and cocaine addiction. To explore how DA modulation regulates the associative learning behavior, we developed an asymmetric reversible neurotransmission-blocking technique in which transmission of each pathway was unilaterally blocked by transmission-blocking tetanus toxin and the transmission on the intact side was pharmacologically manipulated by local infusion of a receptor-specific agonist or antagonist. This approach revealed that the activation of D1 receptors and the inactivation of D2 receptors postsynaptically control reward learning/cocaine addiction and aversive learning in a direct pathway-specific and indirect pathway-specific manner, respectively. Furthermore, this study demonstrated that aversive learning is elicited by elaborate actions of NMDA receptors, adenosine A2a receptors, and endocannabinoid CB1 receptors, which serve as key neurotransmitter receptors in inducing long-term potentiation in the indirect pathway. Thus, reward and aversive learning is regulated by pathway-specific neural plasticity via selective transmitter receptors in the NAc circuit.
authors.affiliation: Department of Systems Biology, Osaka Bioscience Institute, Suita, Osaka 565-0874, Japan. hikida@tk.med.kyoto-u.ac.jp
authors.forename: Takatoshi
authors.initials: T
authors.lastname: Hikida
authors.forename: Satoshi
authors.initials: S
authors.lastname: Yawata
authors.forename: Takashi
authors.initials: T
authors.lastname: Yamaguchi
authors.forename: Teruko
authors.initials: T
authors.lastname: Danjo
authors.forename: Toshikuni
authors.initials: T
authors.lastname: Sasaoka
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Wang
authors.forename: Shigetada
authors.initials: S
authors.lastname: Nakanishi
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001245:Association Learning / Q000502:physiology*; D001362:Avoidance Learning / Q000502:physiology*; D019970:Cocaine-Related Disorders / Q000503:physiopathology*; D006801:Humans; D051379:Mice; D009434:Neural Pathways / Q000378:metabolism; D009473:Neuronal Plasticity / Q000502:physiology*; D009714:Nucleus Accumbens / Q000502:physiology*; D043705:Receptor, Adenosine A2A / Q000378:metabolism; D043884:Receptor, Cannabinoid, CB1 / Q000378:metabolism; D017447:Receptors, Dopamine D1 / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D012201:Reward; D013744:Tetanus Toxin
chemical_list: D043705:Receptor, Adenosine A2A; D043884:Receptor, Cannabinoid, CB1; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D016194:Receptors, N-Methyl-D-Aspartate; D013744:Tetanus Toxin