ide–sensitive factor) (33–35)orAP2(36 ) maybe required for export of functional heteromericreceptor complexes and/or stabilization of thesecomplexes at the cell surface.Our results suggest that phosphorylationof GluR2 Ser880is necessary for LTD induc-tion. In Purkinje cells transfected with GluR2K882A, which presumably contain at leastsome GluR2 K882A/GluR3 and/or GluR2K882A/GluR4c heteromeric receptor com-plexes, the presence of a PKC consensus siteon subunits other than GluR2 appears to beinsufficient to enable LTD. It is unknownwhether the corresponding serines on GluR3and GluR4c are indeed phosphorylated byPKC or if upstream sequence differences anddifferential protein binding render these sub-units incapable of supporting LTD.Previous attempts to test the involvementof cerebellar LTD in motor learning para-digms have relied on drugs or genetic manip-ulations that act early in the LTD inductionsignaling cascade, either at receptors or sec-ond messengers (1). These studies have beenlimited owing to the nonspecific nature of themanipulations (e.g., disruption of mGluR1 orPKC function). A GluR2 K882A knock-inmouse could provide the first strong test ofthe hypothesis that cerebellar LTD is requiredfor certain forms of motor learning.References and Notes1. M. F. Bear, D. J. Linden, in The Synapse, W. M. Cowan,T. Sudhof, C. F. Stevens, Eds. ( Johns Hopkins, Balti-more, MD, 2000), pp. 455–517.2. C. Hansel, D. J. Linden, E. D’Angelo, Nature Neurosci.4, 467 (2001).3. F. Crepel, M. Krupa, Brain Res. 458, 397 (1988).4. D. J. Linden, J. A. Connor, Science 254, 1656 (1991).5. N. A. Hartell, NeuroReport 5, 833 (1994).6. C. I. De Zeeuw et al., Neuron 20, 495 (1998).7. J. H. Freeman, T. Shi, B. G. Schreurs, NeuroReport 9,2237 (1998).8. J. Goossens et al., J. Neurosci. 21, 5813 (2001).9. M. Ito, M. Sakurai, P. Tongroach, J. Physiol.(London)324, 113 (1982).10. D. J. Linden, M. H. Dickinson, M. Smeyne, J. A. Connor,Neuron 7, 81 (1991).11. D. J. Linden, Learn. Mem.(Cold Spring Harbor) 1, 121(1994).12. K. Narasimhan, D. J. Linden, Neuron 17, 333 (1996).13. D. J. Linden, Proc. Natl. Acad. Sci. U.S.A. 98, 14066(2001).14. S. Matsuda, T. Launey, S. Mikawa, H. Hirai, EMBO J.19, 2765 (2000).15. Y.-T. Wang, D. J. Linden, Neuron 25, 635 (2000).16. J. Xia, H. J. Chung,, C. Wihler, R. L. Huganir, D. J.Linden, Neuron 28, 499 (2000).17. S. Matsuda, S. Mikawa, H. Hirai, J. Neurochem. 73,1765 (1999).18. H. J. Chung, J. Xia, R. H. Scannevin, X. Zhang, R. L.Huganir, J. Neurosci. 20, 7258 (2000).19. J. L. Perez et al., J. Neurosci. 21, 5417 (2001).20. H. Dong et al., Nature 386, 279 (1997).21. P. Osten et al., Neuron 27, 313 (2000).22. B. E. Kemp, R. B. Pearson, Trends Biochem. Sci. 15,342 (1990).23. Single-letter abbreviations for the amino acid resi-dues are as follows: A, Ala; C, Cys; D, Asp; E, Glu; F,Phe; G, Gly; H, His; I, Ile; K, Lys; L, Leu; M, Met; N, Asn;P, Pro; Q, Gln; R, Arg; S, Ser; T, Thr; V, Val; W, Trp; X,any amino acid; and Y, Tyr.24. A. Y. Hung, M. Sheng, J. Biol. Chem. 277, 5699(2001).25. We obtained polyclonal antiserum directed against aGluR2 carboxy-terminal peptide phosphorylated atSer880as previously described (18). To account for thepossibility that mutation of Lys882interferes with therecognition of phosphorylated Ser880by this antibody,we purified polyclonal antiserum on an affinity columnconsisting of a bovine serum albumin (BSA)-conjugatedGluR2 carboxy-terminal peptide containing the K882Amutation (KVYGIEpS*VAI; pS* ⫽ phosphoSer880).26. N. Burnashev, H. Monyer, P. H. Seeburg, B. Sakmann,Neuron 8, 189 (1992).27. Z. Jia et al., Neuron 17, 945 (1996).28. M. I. Daw et al., Neuron 28, 873 (2000).29. C. H. Kim et al., Proc. Natl. Acad. Sci. U.S.A. 98:11725 (2001).30. M. Eto, R. Bock, D. L. Brautigan, D. J. Linden, Neuron36, 1145 (2002).31. M. Ito, Physiol. Rev. 81, 1143 (2001).32. See supporting data on Science Online.33. A. Nishimune et al., Neuron 21, 87 (1998).34. P. Osten et al., Neuron 21, 99 (1998).35. I. Song et al., Neuron 21, 393 (1998).36. S. H. Lee, L. Liu, Y.-T. Wang, M. Sheng, Neuron 36, 661(2002).37. Thanks to R. Bock for skillful technical assistance, K.Takamiya for advice on PCR genotyping, and mem-bers of the Huganir and Linden labs for helpful com-ments. This work was supported by HHMI and USPHSNS36715 (R.L.H.), USPHS MH51106 and MH01590(D.J.L.) and the Develbiss Fund (D.J.L.).Supporting Online Materialwww.sciencemag.org/cgi/content/full/300/5626/1751/DC1Materials and MethodsFig. S1References29 January 2003; accepted 6 May 2003The Neural Basis of EconomicDecision-Making in theUltimatum GameAlan G. Sanfey,1,3* James K. Rilling,1* Jessica A. Aronson,2Leigh E. Nystrom,1,2Jonathan D. Cohen1,2,4The nascent field of neuroeconomics seeks to ground economic decision-making in the biological substrate of the brain. We used functional magneticresonance imaging of Ultimatum Game players to investigate neural substratesof cognitive and emotional processes involved in economic decision-making. Inthis game, two players split a sum of money; one player proposes a division andthe other can accept or reject this. We scanned players as they responded tofair and unfair proposals. Unfair offers elicited activity in brain areas related toboth emotion (anterior insula) and cognition (dorsolateral prefrontal cortex).Further, significantly heightened activity in anterior insula for rejected unfairoffers suggests an important role for emotions in decision-making.Standard economic models of human decision-making (such as utility theory) have typicallyminimized or ignored the influence of emotionson people’s decision-making behavior, idealiz-ing the decision-maker as a perfectly rationalcognitive machine. However, in recent yearsthis assumption has been challenged by behav-ioral economists, who have identified additionalpsychological and emotional factors that influ-ence decision-making (1, 2), and recently re-searchers have begun using neuroimaging toexamine behavior in economic games (3). Thisstudy applies functional neuroimaging tech-niques to investigate the relative contributions ofcognitive and emotional processes to humansocial decision-making.The limitations of the standard economicmodel are effectively illustrated by empiricalfindings from a simple game known as theUltimatum Game. In the Ultimatum Game, twoplayers are given the opportunity to split a sumof money. One player is deemed the proposerand the other, the responder. The proposermakes an offer as to how this money