The DOI matches its Crossref record; 55 of the 55 references it cites were found in a registry or an index.
Distinct Roles of Synaptic Transmission in Direct and Indirect Striatal Pathways to Reward and Aversive Behavior
Open accessAbstract
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.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“inhibition of striatal D2R or activation of D1R-expressing striatal neurons (which mediate signalling in the striatal direct pathway) enhance the sensitivity to the rewarding effects of drugs (71–73).”
From Obesity and addiction: Neurobiological overlaps (2013) · cites this paper as [72]
Citations
Cites
The functional anatomy of basal ganglia disorders
Albin, R. L., Young, A. B., & Penney, J. B. (1989) · Trends in Neurosciences · doi:10.1016/0166-2236(89)90074-x · Cited by 5,353
Di Chiara, G., & Imperato, A. (1988) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.85.14.5274 · Cited by 4,733
Functional architecture of basal ganglia circuits: neural substrates of parallel processing
Alexander, G. E., & Crutcher, M. D. (1990) · Trends in Neurosciences · doi:10.1016/0166-2236(90)90107-l · Cited by 4,131
D 1 and D 2 Dopamine Receptor-regulated Gene Expression of Striatonigral and Striatopallidal Neurons
Gerfen, C. R., Engber, T. M., Mahan, L. C., Susel, Z., Chase, T. N., Monsma, F. J., & Sibley, D. R. (1990) · Science · doi:10.1126/science.2147780 · Cited by 2,967
NEURAL MECHANISMS OF ADDICTION: The Role of Reward-Related Learning and Memory
Hyman, S. E., Malenka, R. C., & Nestler, E. J. (2006) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.29.051605.113009 · Cited by 2,647
Kalivas, P., & Stewart, J. (1991) · Brain research. Brain research reviews · doi:10.1016/0165-0173(91)90007-u · Cited by 2,087
Schiavo, G., Benfenati, F., Poulain, B., Rossetto, O., de Laureto, P. P., DasGupta, B. R., & Montecucco, C. (1992) · Nature · doi:10.1038/359832a0 · Cited by 1,803
Tzschentke, T. M. (2007) · Addiction Biology · doi:10.1111/j.1369-1600.2007.00070.x · Cited by 1,336
Phasic Firing in Dopaminergic Neurons Is Sufficient for Behavioral Conditioning
Tsai, H.-C., Zhang, F., Adamantidis, A., Stuber, G. D., Bonci, A., de Lecea, L., & Deisseroth, K. (2009) · Science · doi:10.1126/science.1168878 · Cited by 1,266
Surmeier, D. J., Ding, J., Day, M., Wang, Z., & Shen, W. (2007) · Trends in Neurosciences · doi:10.1016/j.tins.2007.03.008 · Cited by 1,203
Dichotomous dopaminergic control of striatal synaptic plasticity
Shen, W., Flajolet, M., Greengard, P., & Surmeier, D. J. (2008) · Science · doi:10.1126/science.1160575 · Cited by 1,190
Hold Your Horses: Impulsivity, Deep Brain Stimulation, and Medication in Parkinsonism
Frank, M. J., Samanta, J., Moustafa, A. A., & Sherman, S. J. (2007) · Science · doi:10.1126/science.1146157 · Cited by 1,162
A translational profiling approach for the molecular characterization of CNS cell types
Heiman, M., Schaefer, A., Gong, S., Peterson, J. D., Day, M., Ramsey, K. E., Suárez-Fariñas, M., Schwarz, C., Stephan, D. A., Surmeier, D. J., et al. (2008) · Cell · doi:10.1016/j.cell.2008.10.028 · Cited by 1,134
Graybiel, A. M. (2000) · Current Biology · doi:10.1016/s0960-9822(00)00593-5 · Cited by 1,051
Regulation of firing of dopaminergic neurons and control of goal-directed behaviors
Grace, A. A., Floresco, S. B., Goto, Y., & Lodge, D. J. (2007) · Trends in Neurosciences · doi:10.1016/j.tins.2007.03.003 · Cited by 1,034
Incubation of cocaine craving after withdrawal
Grimm, J. W., Hope, B. T., Wise, R. A., & Shaham, Y. (2001) · Nature · doi:10.1038/35084134 · Cited by 1,031
Schultz, W. (2007) · Trends in Neurosciences · doi:10.1016/j.tins.2007.03.007 · Cited by 1,028
Frank, M. J. (2005) · Journal of Cognitive Neuroscience · doi:10.1162/0898929052880093 · Cited by 925
Preferential activation of midbrain dopamine neurons by appetitive rather than aversive stimuli
Mirenowicz, J., & Schultz, W. (1996) · Nature · doi:10.1038/379449a0 · Cited by 829
Phasic excitation of dopamine neurons in ventral VTA by noxious stimuli
Brischoux, F., Chakraborty, S., Brierley, D. I., & Ungless, M. A. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0811507106 · Cited by 801
Uniform Inhibition of Dopamine Neurons in the Ventral Tegmental Area by Aversive Stimuli
Ungless, M. A., Magill, P. J., & Bolam, J. P. (2004) · Science · doi:10.1126/science.1093360 · Cited by 782
The distribution of substance P immunoreactive fibers in the rat central nervous system
Cuello, A. C., & Kanazawa, I. (1978) · The Journal of Comparative Neurology · doi:10.1002/cne.901780108 · Cited by 728
PYCOCK, C. (1980) · Neuroscience · doi:10.1016/0306-4522(80)90048-2 · Cited by 610
Dopaminergic modulation of limbic and cortical drive of nucleus accumbens in goal-directed behavior
Goto, Y., & Grace, A. A. (2005) · Nature Neuroscience · doi:10.1038/nn1471 · Cited by 576
Importance of unpredictability for reward responses in primate dopamine neurons
Mirenowicz, J., & Schultz, W. (1994) · Journal of Neurophysiology · doi:10.1152/jn.1994.72.2.1024 · Cited by 544
Richfield, E. K., Penney, J. B., & Young, A. B. (1989) · Neuroscience · doi:10.1016/0306-4522(89)90168-1 · Cited by 448
FACS-array profiling of striatal projection neuron subtypes in juvenile and adult mouse brains
Lobo, M. K., Karsten, S. L., Gray, M., Geschwind, D. H., & Yang, X. W. (2006) · Nature Neuroscience · doi:10.1038/nn1654 · Cited by 411
Basal ganglia and movement disorders: an update
Chesselet, M., & Delfs, J. M. (1996) · Trends in Neurosciences · doi:10.1016/0166-2236(96)10052-7 · Cited by 409
Neural mechanisms of reward-related motor learning
Wickens, J. R., Reynolds, J. N., & Hyland, B. I. (2003) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2003.10.013 · Cited by 284
Cocaine Regulates MEF2 to Control Synaptic and Behavioral Plasticity
Pulipparacharuvil, S., Renthal, W., Hale, C. F., Taniguchi, M., Xiao, G., Kumar, A., Russo, S. J., Sikder, D., Dewey, C. M., Davis, M. M., et al. (2008) · Neuron · doi:10.1016/j.neuron.2008.06.020 · Cited by 281
Looking BAC at striatal signaling: cell-specific analysis in new transgenic mice
Valjent, E., Bertran‐Gonzalez, J., Hervé, D., Fisone, G., & Girault, J. (2009) · Trends in Neurosciences · doi:10.1016/j.tins.2009.06.005 · Cited by 269
Basal ganglia and movement disorders: an update
Chesselet, M. (1996) · Trends in Neurosciences · doi:10.1016/s0166-2236(96)10052-7 · Cited by 266
Masugi, M., Yokoi, M., Shigemoto, R., Muguruma, K., Watanabe, Y., Sansig, G., van der Putten, H., & Nakanishi, S. (1999) · The Journal of Neuroscience · doi:10.1523/jneurosci.19-03-00955.1999 · Cited by 211
Self-citationGoto, Y., & Grace, A. A. (2005) · Neuron · doi:10.1016/j.neuron.2005.06.017 · Cited by 204
The pars reticulata of the substantia nigra: a window to basal ganglia output
Deniau, J., Mailly, P., Maurice, N., & Charpier, S. (2007) · Progress in brain research · doi:10.1016/s0079-6123(06)60009-5 · Cited by 202
A novel strategy for the treatment of cocaine addiction
Dewey, S. L., Morgan, A. E., Ashby, C. R., Horan, B., Kushner, S. A., Logan, J., Volkow, N. D., Fowler, J. S., Gardner, E. L., & Brodie, J. D. (1998) · Synapse · doi:10.1002/(sici)1098-2396(199810)30:2 · Cited by 194
Lack of Self-Administration of Cocaine in Dopamine D 1 Receptor Knock-Out Mice
Caine, S. B., Thomsen, M., Gabriel, K. I., Berkowitz, J. S., Gold, L. H., Koob, G. F., Tonegawa, S., Zhang, J., & Xu, M. (2007) · The Journal of Neuroscience · doi:10.1523/jneurosci.2284-07.2007 · Cited by 183
Synaptic Integration Mediated by Striatal Cholinergic Interneurons in Basal Ganglia Function
Kaneko, S., Hikida, T., Watanabe, D., Ichinose, H., Nagatsu, T., Kreitman, R. J., Pastan, I. H., & Nakanishi, S. (2000) · Science · doi:10.1126/science.289.5479.633 · Cited by 166
Self-citationLerchner, W., Xiao, C., Nashmi, R., Slimko, E. M., van Trigt, L., Lester, H. A., & Anderson, D. J. (2007) · Neuron · doi:10.1016/j.neuron.2007.02.030 · Cited by 163
Basal Ganglia Mechanisms of Reward‐Oriented Eye Movement
Hikosaka, O. (2007) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1390.012 · Cited by 159
Hikida, T., Kitabatake, Y., Pastan, I. H., & Nakanishi, S. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0631749100 · Cited by 157
Self-citationThe Role of an Amygdalo-Nigrostriatal Pathway in Associative Learning
Han, J., McMahan, R. W., Holland, P. C., & Gallagher, M. (1997) · Journal of Neuroscience · doi:10.1523/jneurosci.17-10-03913.1997 · Cited by 154
Yamamoto, M., Wada, N., Kitabatake, Y., Watanabe, D., Anzai, M., Yokoyama, M., Teranishi, Y., & Nakanishi, S. (2003) · Journal of Neuroscience · doi:10.1523/jneurosci.23-17-06759.2003 · Cited by 150
Self-citationXu, M., Guo, Y. H., Vorhees, C. V., & Zhang, J. (2000) · Brain Research · doi:10.1016/s0006-8993(99)02258-1 · Cited by 148
Retained cocaine conditioned place preference in D1 receptor deficient mice
Miner, L. L., Drago, J., Chamberlain, P. M., Donovan, D. M., & Uhl, G. R. (1995) · Neuroreport · doi:10.1097/00001756-199511270-00011 · Cited by 112
Smith, J. W., Fetsko, L. A., Xu, R., & Wang, Y. (2002) · Neuroscience · doi:10.1016/s0306-4522(02)00257-9 · Cited by 103
Increased sensitivity to cocaine by cholinergic cell ablation in nucleus accumbens
Hikida, T., Kaneko, S., Isobe, T., Kitabatake, Y., Watanabe, D., Pastan, I. H., & Nakanishi, S. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.231488998 · Cited by 98
Self-citationCoizet, V., Dommett, E. J., Redgrave, P., & Overton, P. G. (2006) · Neuroscience · doi:10.1016/j.neuroscience.2006.01.030 · Cited by 92
Welter, M., Vallone, D., Samad, T. A., Méziane, H., Usiello, A., & Borrelli, E. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0610790104 · Cited by 87
Dopamine receptors in canine caudate nucleus
Maeno, H. (1982) · Molecular and Cellular Biochemistry · doi:10.1007/bf00423094 · Cited by 74
Dual Role of Medial A10 Dopamine Neurons in Affective Encoding
Liu, Z., Shin, R. S., & Ikemoto, S. (2008) · Neuropsychopharmacology · doi:10.1038/npp.2008.4 · Cited by 73
Conditioned eyeblink learning is formed and stored without cerebellar granule cell transmission
Wada, N., Kishimoto, Y., Watanabe, D., Kano, M., Hirano, T., Funabiki, K., & Nakanishi, S. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0708165104 · Cited by 68
Self-citationBaker, D. L., Khroyan, T. V., O'Dell, L. E., Fuchs, R. A., & Neisewander, J. L. (1996) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(25)20979-x · Cited by 63
The distribution and functions of the enkephalins.
Miller, R. J., & Pickel, V. M. (1980) · Journal of Histochemistry & Cytochemistry · doi:10.1177/28.8.7003009 · Cited by 57
Dopaminergic Regulation of Immediate Early Gene Expression in the Basal Ganglia
Marshall, J. F., Ruskin, D. N., & LaHoste, G. J. (1997) · Advances in pharmacology · doi:10.1016/s1054-3589(08)60839-x · Cited by 4
Cited by
Sorted by citations
Dopamine in motivational control: rewarding, aversive, and alerting
Bromberg-Martin, E. S., Matsumoto, M., & Hikosaka, O. (2010) · Neuron · doi:10.1016/j.neuron.2010.11.022 · Cited by 2,396
Modulation of Striatal Projection Systems by Dopamine
Gerfen, C. R., & Surmeier, D. J. (2011) · Annual Review of Neuroscience · doi:10.1146/annurev-neuro-061010-113641 · Cited by 1,700
The brain on drugs: from reward to addiction
Volkow, N. D., & Morales, M. (2015) · Cell · doi:10.1016/j.cell.2015.07.046 · Cited by 1,306
Drug-evoked synaptic plasticity in addiction: from molecular changes to circuit remodeling
Lüscher, C., & Malenka, R. C. (2011) · Neuron · doi:10.1016/j.neuron.2011.01.017 · Cited by 1,105
Distinct roles for direct and indirect pathway striatal neurons in reinforcement
Kravitz, A. V., Tye, L. D., & Kreitzer, A. C. (2012) · Nature Neuroscience · doi:10.1038/nn.3100 · Cited by 972
Metadata
- Authors
- Hikida, T., Kimura, K., Wada, N., Funabiki, K., & Nakanishi, S.
- Affiliations
- Japan Science and Technology Agency (JP)
- Kyoto University (JP)
- Corresponding author
- Nakanishi, Shigetada
- ORCID
- Hikida, Takatoshi
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2010-06
- Volume
- 66
- Issue
- 6
- Pages
- 896-907
- ISSN
- 0896-6273 (ISSN-L)
- OpenAlex
- W1973788414
- Cited by
- 592
- References
- 55
- Citations by year
- 2026: 13 · 2025: 36 · 2024: 24 · 2023: 35 · 2022: 36 · 2021: 47 · 2020: 34 · 2019: 37 · 2018: 42 · 2017: 38 · 2016: 46 · 2015: 42 · 2014: 54 · 2013: 47 · 2012: 28
- FWCI
- 13.95
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Ministry of Education, Culture, Sports, Science and Technology
- Precursory Research for Embryonic Science and Technology
- Takeda Science Foundation
- Uehara Memorial Foundation
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Health Sciences › Medicine › Clinical Neurology › Deep Brain Stimulation and Movement Disorders
- Keywords
- basal ganglia, dopamine, synaptic transmission, tetanus toxin, reward learning, aversive behavior, cocaine sensitization, psychostimulant effects, drug addiction
- MeSH terms
- Action Potentials, Adaptation, Physiological, Dependovirus, Central Nervous System Stimulants, Analysis of Variance, Animals, Avoidance Learning, Behavior, Animal, Cholera Toxin, Cocaine, Conditioning, Operant, Corpus Striatum, Doxycycline, Enzyme-Linked Immunosorbent Assay, Gene Expression Regulation, Methamphetamine, Mice, Transgenic, Neural Pathways, Synaptic Transmission, Neurons, Neurotoxins, Recombinant Fusion Proteins, Reward, RNA, Messenger, Substantia Nigra, Tetanus Toxin, Transfection, Proto-Oncogene Proteins c-fos, Dopamine Uptake Inhibitors, Vesicle-Associated Membrane Protein 2, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review