Lateral habenula as a source of negative reward signals in dopamine neurons

被引:933
作者
Matsumoto, Masayuki [1 ]
Hikosaka, Okihide [1 ]
机构
[1] NEI, Sensorimotor Res Lab, NIH, Bethesda, MD 20892 USA
基金
美国国家卫生研究院;
关键词
D O I
10.1038/nature05860
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Midbrain dopamine neurons are key components of the brain's reward system(1), which is thought to guide reward-seeking behaviours(2-4). Although recent studies have shown how dopamine neurons respond to rewards and sensory stimuli predicting reward(1,5,6), it is unclear which parts of the brain provide dopamine neurons with signals necessary for these actions. Here we show that the primate lateral habenula, part of the structure called the epithalamus, is a major candidate for a source of negative reward-related signals in dopamine neurons. We recorded the activity of habenula neurons and dopamine neurons while rhesus monkeys were performing a visually guided saccade task with positionally biased reward outcomes(7). Many habenula neurons were excited by a no-reward-predicting target and inhibited by a reward-predicting target. In contrast, dopamine neurons were excited and inhibited by reward-predicting and no-reward-predicting targets, respectively. Each time the rewarded and unrewarded positions were reversed, both habenula and dopamine neurons reversed their responses as the bias in saccade latency reversed. In unrewarded trials, the excitation of habenula neurons started earlier than the inhibition of dopamine neurons. Furthermore, weak electrical stimulation of the lateral habenula elicited strong inhibitions in dopamine neurons. These results suggest that the inhibitory input from the lateral habenula plays an important role in determining the reward-related activity of dopamine neurons.
引用
收藏
页码:1111 / U11
页数:7
相关论文
共 31 条
[1]   The role of the habenular complex in the elevation of dorsal raphe nucleus serotonin and the changes in the behavioral responses produced by uncontrollable stress [J].
Amat, J ;
Sparks, PD ;
Matus-Amat, P ;
Griggs, J ;
Watkins, LR ;
Maier, SF .
BRAIN RESEARCH, 2001, 917 (01) :118-126
[2]  
CALDECOTTHAZARD S, 1988, J NEUROSCI, V8, P1951
[3]  
CHRISTOPH GR, 1986, J NEUROSCI, V6, P613
[4]   Opponent interactions between serotonin and dopamine [J].
Daw, ND ;
Kakade, S ;
Dayan, P .
NEURAL NETWORKS, 2002, 15 (4-6) :603-616
[5]   STIMULANT-INDUCED PSYCHOSIS, THE DOPAMINE THEORY OF SCHIZOPHRENIA, AND THE HABENULA [J].
ELLISON, G .
BRAIN RESEARCH REVIEWS, 1994, 19 (02) :223-239
[6]   Simultaneous recording of spontaneous activities and nociceptive responses from neurons in the pars compacta of substantia nigra and in the lateral habenula [J].
Gao, DM ;
Hoffman, D ;
Benabid, AL .
EUROPEAN JOURNAL OF NEUROSCIENCE, 1996, 8 (07) :1474-1478
[7]   EFFERENT CONNECTIONS OF THE HABENULAR NUCLEI IN THE RAT [J].
HERKENHAM, M ;
NAUTA, WJH .
JOURNAL OF COMPARATIVE NEUROLOGY, 1979, 187 (01) :19-47
[8]   Basal ganglia orient eyes to reward [J].
Hikosaka, O ;
Nakamura, K ;
Nakahara, H .
JOURNAL OF NEUROPHYSIOLOGY, 2006, 95 (02) :567-584
[9]  
Houk J., 1995, Models ofInformation Processing in the Basal Ganglia, P249
[10]   Reward-predicting activity of dopamine and caudate neurons - A possible mechanism of motivational control of saccadic eye movement [J].
Kawagoe, R ;
Takikawa, Y ;
Hikosaka, O .
JOURNAL OF NEUROPHYSIOLOGY, 2004, 91 (02) :1013-1024