Endocannabinoid-mediated rescue of striatal LTD and motor deficits in Parkinson's disease models
Abstract
The striatum is a major forebrain nucleus that integrates cortical and thalamic afferents and forms the input nucleus of the basal ganglia. Striatal projection neurons target the substantia nigra pars reticulata (direct pathway) or the lateral globus pallidus (indirect pathway). Imbalances between neural activity in these two pathways have been proposed to underlie the profound motor deficits observed in Parkinson's disease and Huntington's disease. However, little is known about differences in cellular and synaptic properties in these circuits. Indeed, current hypotheses suggest that these cells express similar forms of synaptic plasticity. Here we show that excitatory synapses onto indirect-pathway medium spiny neurons (MSNs) exhibit higher release probability and larger N-methyl-d-aspartate receptor currents than direct-pathway synapses. Moreover, indirect-pathway MSNs selectively express endocannabinoid-mediated long-term depression (eCB-LTD), which requires dopamine D2 receptor activation. In models of Parkinson's disease, indirect-pathway eCB-LTD is absent but is rescued by a D2 receptor agonist or inhibitors of endocannabinoid degradation. Administration of these drugs together in vivo reduces parkinsonian motor deficits, suggesting that endocannabinoid-mediated depression of indirect-pathway synapses has a critical role in the control of movement. These findings have implications for understanding the normal functions of the basal ganglia, and also suggest approaches for the development of therapeutic drugs for the treatment of striatal-based brain disorders.
Integrity signals
Registry
Cites
Statistics
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?
Impaired neuroplasticity under dopamine denervation may give rise to aberrant learning that further impairs automatic motor behavior.
“which may give rise to an aberrant learning that further impairs automatic motor behavior 45, 46.”
From Exercise-enhanced neuroplasticity targeting motor and cognitive circuitry in Parkinson's disease (2013) · cites this paper as [46]
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 · see citing works
Short-Term Synaptic Plasticity
Zucker, R. S., & Regehr, W. G. (2002) · Annual Review of Physiology · doi:10.1146/annurev.physiol.64.092501.114547 · Cited by 5,068 · see citing works
The Glutamate Receptor Ion Channels
Dingledine, R., Borges, K., Bowie, D., & Traynelis, S. F. (1999) · Pharmacological Reviews · doi:10.1016/s0031-6997(24)01394-2 · Cited by 3,554 · see citing works
The Synaptic Organization of the Brain
(2004) · Oxford University Press eBooks · doi:10.1093/acprof:oso/9780195159561.001.1 · Cited by 3,550 · see citing works
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 · see citing works
A gene expression atlas of the central nervous system based on bacterial artificial chromosomes
Gong, S., Zheng, C., Doughty, M. L., Losos, K., Didkovsky, N., Schambra, U. B., Nowak, N. J., Joyner, A., Leblanc, G., Hatten, M. E., et al. (2003) · Nature · doi:10.1038/nature02033 · Cited by 2,108 · see citing works
Modulation of anxiety through blockade of anandamide hydrolysis
Kathuria, S., Gaetani, S., Fegley, D., Valiño, F., Duranti, A., Tontini, A., Mor, M., Tarzia, G., Rana, G. L., Calignano, A., et al. (2003) · Nature Medicine · doi:10.1038/nm803 · Cited by 1,293 · see citing works
Increased mortality, hypoactivity, and hypoalgesia in cannabinoid CB1 receptor knockout mice
Zimmer, A., Zimmer, A. M., Hohmann, A. G., Herkenham, M. A., & Bonner, T. I. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.10.5780 · Cited by 1,065 · see citing works
Graybiel, A. M. (2000) · Current Biology · doi:10.1016/s0960-9822(00)00593-5 · Cited by 1,051 · see citing works
Synaptic organisation of the basal ganglia
Bolam, J. P., Hanley, J. J., Booth, P. A. C., & Bevan, M. D. (2000) · Journal of Anatomy · doi:10.1046/j.1469-7580.2000.19640527.x · Cited by 950 · see citing works
Dopamine activation of endogenous cannabinoid signaling in dorsal striatum
Giuffrida, A., Parsons, L. H., Kerr, T. M., de Fonseca, F. R., Navarro, M. A., & Piomelli, D. (1999) · Nature Neuroscience · doi:10.1038/7268 · Cited by 771 · see citing works
Postsynaptic endocannabinoid release is critical to long-term depression in the striatum
Gerdeman, G. L., Ronesi, J. A., & Lovinger, D. M. (2002) · Nature Neuroscience · doi:10.1038/nn832 · Cited by 767 · see citing works
The Synaptic Organization of the Brain
Freemon, F. R. (1980) · JAMA · doi:10.1001/jama.1980.03300440052037 · Cited by 709 · see citing works
Long-term synaptic depression in the striatum: physiological and pharmacological characterization
Calabresi, P., Maj, R., Pisani, A., Mercuri, N. B., & Bernardi, G. (1992) · Journal of Neuroscience · doi:10.1523/jneurosci.12-11-04224.1992 · Cited by 673 · see citing works
Parkinsonian-like locomotor impairment in mice lacking dopamine D2 receptors
Baik, J., Picetti, R., Saiardi, A., Thiriet, G., Dierich, A., Depaulis, A., LeMeur, M., & Borrelli, E. (1995) · Nature · doi:10.1038/377424a0 · Cited by 651 · see citing works
Animal models of Parkinson's disease
Betarbet, R. S., Sherer, T., & Greenamyre, J. T. (2002) · BioEssays · doi:10.1002/bies.10067 · Cited by 600 · see citing works
Practice parameter: Thymectomy for autoimmune myasthenia gravis (an evidence-based review) [RETIRED]
Gronseth, G., & Barohn, R. J. (2000) · Neurology · doi:10.1212/wnl.55.1.7 · Cited by 583 · see citing works
Wang, Z., Li, K., Day, M., Ronesi, J. A., Yin, H. H., Ding, J., Tkatch, T., Lovinger, D. M., & Surmeier, D. J. (2006) · Neuron · doi:10.1016/j.neuron.2006.04.010 · Cited by 513 · see citing works
It could be habit forming: drugs of abuse and striatal synaptic plasticity
Gerdeman, G. L., Partridge, J. G., Lupica, C. R., & Lovinger, D. M. (2003) · Trends in Neurosciences · doi:10.1016/s0166-2236(03)00065-1 · Cited by 480 · see citing works
Mallet, N. P., Ballion, B., Moine, C. L., & Gonon, F. (2006) · Journal of Neuroscience · doi:10.1523/jneurosci.4439-05.2006 · Cited by 413 · see citing works
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 · see citing works
Kreitzer, A. C., & Malenka, R. C. (2005) · Journal of Neuroscience · doi:10.1523/jneurosci.2959-05.2005 · Cited by 358 · see citing works
Self-citationCompton, D. M., Aceto, M. D. G., Lowe, J. A., III, & Martin, B. R. (1996) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(25)12911-x · Cited by 357 · see citing works
Schwarting, R. K. W., & Huston, J. P. (1996) · Progress in Neurobiology · doi:10.1016/s0301-0082(96)00015-9 · Cited by 345 · see citing works
Gubellini, P., Picconi, B., Bari, M., Battista, N., Calabresi, P., Centonze, D., Bernardi, G., Finazzi‐Agrò, A., & Maccarrone, M. (2002) · Journal of Neuroscience · doi:10.1523/jneurosci.22-16-06900.2002 · Cited by 321 · see citing works
Marzo, V. D., Hill, M. P., Bisogno, T., Crossman, A. R., & Brotchie, J. M. (2000) · The FASEB Journal · doi:10.1096/fasebj.14.10.1432 · Cited by 303 · see citing works
Abnormal Synaptic Plasticity in the Striatum of Mice Lacking Dopamine D2 Receptors
Calabresi, P., Saiardi, A., Pisani, A., Baik, J., Centonze, D., Mercuri, N. B., Bernardi, G., & Borrelli, E. (1997) · Journal of Neuroscience · doi:10.1523/jneurosci.17-12-04536.1997 · Cited by 287 · see citing works
Selective inhibition of 2-AG hydrolysis enhances endocannabinoid signaling in hippocampus
Makara, J. K., Mor, M., Fegley, D., Szabó, S. I., Kathuria, S., Astarita, G., Duranti, A., Tontini, A., Tarzia, G., Rivara, S., et al. (2005) · Nature Neuroscience · doi:10.1038/nn1521 · Cited by 231 · see citing works
Marzo, V. D. (2000) · The FASEB Journal · doi:10.1096/fj.14.10.1432 · Cited by 219 · see citing works
Dopamine-dependent synaptic plasticity in striatum during in vivo development
Tang, K., Low, M. J., Grandy, D. K., & Lovinger, D. M. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.98.3.1255 · Cited by 171 · see citing works
Glutamate receptor ion channels.
Mayer, M. (2005) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2005.05.004 · Cited by 163 · see citing works
Dopamine agonists, receptor selectivity and dyskinesia induction in Parkinsonʼs disease
Jenner, P. G. (2003) · Current Opinion in Neurology · doi:10.1097/00019052-200312001-00002 · Cited by 136 · see citing works
Pathophysiologic basis of surgery for Parkinson's disease.
Obeso, J. A., Rodríguez-Oroz, M. C., Rodriguez, M., Macıás, R., Álvarez, L., Guridi, J., Vitek, J. L., & DeLong, M. R. (2000) · PubMed · Cited by 126 · see citing works
URB754 Has No Effect on the Hydrolysis or Signaling Capacity of 2-AG in the Rat Brain
Saario, S. M., Palomäki, V., Lehtonen, M., Nevalainen, T., Järvinen, T., & Laitinen, J. T. (2006) · Chemistry & Biology · doi:10.1016/j.chembiol.2006.07.008 · Cited by 34 · see citing works
Flagged first, then by citations
1 of the 35 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Synaptic Plasticity: Multiple Forms, Functions, and Mechanisms
Citri, A., & Malenka, R. C. (2008) · Neuropsychopharmacology · doi:10.1038/sj.npp.1301559 · Cited by 2,323 · see citing works
Self-citationRegulation of parkinsonian motor behaviours by optogenetic control of basal ganglia circuitry
Kravitz, A. V., Freeze, B. S., Parker, P. R. L., Kay, K., Thwin, M. T., Deisseroth, K., & Kreitzer, A. C. (2010) · Nature · doi:10.1038/nature09159 · Cited by 1,885 · see citing works
Self-citationModulation 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 · see citing works
Endocannabinoid-Mediated Control of Synaptic Transmission
Kano, M., Ohno‐Shosaku, T., Hashimotodani, Y., Uchigashima, M., & Watanabe, M. (2009) · Physiological Reviews · doi:10.1152/physrev.00019.2008 · Cited by 1,529 · see citing works
Synaptic plasticity and addiction
Kauer, J. A., & Malenka, R. C. (2007) · Nature Reviews Neuroscience · doi:10.1038/nrn2234 · Cited by 1,397 · see citing works
Self-citationSurmeier, 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 · see citing works
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 · see citing works
Neuronal Reward and Decision Signals: From Theories to Data
Schultz, W. (2015) · Physiological Reviews · doi:10.1152/physrev.00023.2014 · Cited by 1,126 · see citing works
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 · see citing works
Self-citationStriatal Plasticity and Basal Ganglia Circuit Function
Kreitzer, A. C., & Malenka, R. C. (2008) · Neuron · doi:10.1016/j.neuron.2008.11.005 · Cited by 1,009 · see citing works
Self-citationCortico-striatal synaptic defects and OCD-like behaviours in Sapap3-mutant mice
Welch, J. M., Lu, J., Rodriguiz, R. M., Trotta, N. C., Peca, J., Ding, J.-D., Feliciano, C., Chen, M., Adams, J. P., Luo, J., et al. (2007) · Nature · doi:10.1038/nature06104 · Cited by 852 · see citing works
Agenesis of the corpus callosum: Genetic, developmental and functional aspects of connectivity
Paul, L. K., Brown, W. S., Adolphs, R., Tyszka, J. M., Richards, L. J., Mukherjee, P., & Sherr, E. H. (2007) · Nature Reviews Neuroscience · doi:10.1038/nrn2107 · Cited by 830 · see citing works
Direct and indirect pathways of basal ganglia: a critical reappraisal
Calabresi, P., Picconi, B., Tozzi, A., Ghiglieri, V., & Filippo, M. D. (2014) · Nature Neuroscience · doi:10.1038/nn.3743 · Cited by 820 · see citing works
Dynamic reorganization of striatal circuits during the acquisition and consolidation of a skill
Yin, H. H., Mulcare, S. P., Hilário, M. R. F., Clouse, E., Holloway, T., Davis, M. I., Hansson, A. C., Lovinger, D. M., & Costa, R. M. (2009) · Nature Neuroscience · doi:10.1038/nn.2261 · Cited by 818 · see citing works
Exercise-enhanced neuroplasticity targeting motor and cognitive circuitry in Parkinson's disease
Petzinger, G. M., Fisher, B. E., McEwen, S., Beeler, J. A., Walsh, J. P., & Jakowec, M. W. (2013) · The Lancet Neurology · doi:10.1016/s1474-4422(13)70123-6 · Cited by 798 · see citing works
Targeting the endocannabinoid system: to enhance or reduce?
Marzo, V. D. (2008) · Nature Reviews Drug Discovery · doi:10.1038/nrd2553 · Cited by 798 · see citing works
Dopaminergic modulation of synaptic transmission in cortex and striatum
Tritsch, N. X., & Sabatini, B. L. (2012) · Neuron · doi:10.1016/j.neuron.2012.09.023 · Cited by 756 · see citing works
Dendritic Excitability and Synaptic Plasticity
Sjöström, P. J., Rancz, E. A., Roth, A., & Häusser, M. (2008) · Physiological Reviews · doi:10.1152/physrev.00016.2007 · Cited by 721 · see citing works
Shen, W., Plotkin, J. L., Francardo, V., Ko, W. K. D., Xie, Z., Li, Q., Fieblinger, T., Wess, J., Neubig, R. R., Lindsley, C. W., et al. (2015) · Neuron · doi:10.1016/j.neuron.2015.10.039 · Cited by 713 · see citing works
Functional organization of the basal ganglia: Therapeutic implications for Parkinson's disease
Obeso, J. A., Rodríguez-Oroz, M. C., Benítez‐Temiño, B., Blesa, F. J., Guridi, J., Marı́n, C., & Rodrı́guez, M. (2008) · Movement Disorders · doi:10.1002/mds.22062 · Cited by 669 · see citing works
Genetic triple dissociation reveals multiple roles for dopamine in reinforcement learning
Frank, M. J., Moustafa, A. A., Haughey, H. M., Curran, T., & Hutchison, K. E. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0706111104 · Cited by 669 · see citing works
Updating dopamine reward signals
Schultz, W. (2013) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2012.11.012 · Cited by 651 · see citing works
Lüscher, C., & Huber, K. M. (2010) · Neuron · doi:10.1016/j.neuron.2010.01.016 · Cited by 627 · see citing works
Bertran‐Gonzalez, J., Bosch‐Bouju, C., Maroteaux, M. J., Matamales, M., Hervé, D., Valjent, E., & Girault, J. (2008) · Journal of Neuroscience · doi:10.1523/jneurosci.1039-08.2008 · Cited by 606 · see citing works
Endocannabinoid signaling as a synaptic circuit breaker in neurological disease
Katona, I., & Freund, T. F. (2008) · Nature Medicine · doi:10.1038/nm.f.1869 · Cited by 579 · see citing works
Physiology and pharmacology of striatal neurons
Kreitzer, A. C. (2009) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.051508.135422 · Cited by 530 · see citing works
Self-citationHigh-throughput electrophysiology: an emerging paradigm for ion-channel screening and physiology
Dunlop, J., Bowlby, M. R., Peri, R., Vasilyev, D. K., & Arias, R. L. (2008) · Nature Reviews Drug Discovery · doi:10.1038/nrd2552 · Cited by 500 · see citing works
Neurotransmitter roles in synaptic modulation, plasticity and learning in the dorsal striatum
Lovinger, D. M. (2010) · Neuropharmacology · doi:10.1016/j.neuropharm.2010.01.008 · Cited by 488 · see citing works
Endocannabinoid Signaling and Long-Term Synaptic Plasticity
Heifets, B. D., & Castillo, P. E. (2009) · Annual Review of Physiology · doi:10.1146/annurev.physiol.010908.163149 · Cited by 488 · see citing works
Dichotomous Anatomical Properties of Adult Striatal Medium Spiny Neurons
Gertler, T. S., Chan, C. S., & Surmeier, D. J. (2008) · Journal of Neuroscience · doi:10.1523/jneurosci.2660-08.2008 · Cited by 469 · see citing works
Habenula: crossroad between the basal ganglia and the limbic system
Hikosaka, O., Sesack, S. R., Lecourtier, L., & Shepard, P. D. (2008) · The Journal of Neuroscience · doi:10.1523/jneurosci.3463-08.2008 · Cited by 432 · see citing works
The ins and outs of the striatum: Role in drug addiction
Yager, L. M., Garcia, A. F., Wunsch, A. M., & Ferguson, S. M. (2015) · Neuroscience · doi:10.1016/j.neuroscience.2015.06.033 · Cited by 421 · see citing works
Dopaminergic dysfunction in schizophrenia: Salience attribution revisited
Heinz, A., & Schlagenhauf, F. (2010) · Schizophrenia Bulletin · doi:10.1093/schbul/sbq031 · Cited by 412 · see citing works
Taverna, S., Ilijic, E., & Surmeier, D. J. (2008) · The Journal of Neuroscience · doi:10.1523/jneurosci.5493-07.2008 · Cited by 399 · see citing works
Microglial CB2 cannabinoid receptors are neuroprotective in Huntington's disease excitotoxicity
Palazuelos, J., Aguado, T., Pazos, M. R., Julien, B., Carrasco, C., Resel, E., Sagredo, O., Benito, C., Romero, J., Azcoitia, I., et al. (2009) · Brain · doi:10.1093/brain/awp239 · Cited by 382 · see citing works
Lobo, M. K., & Nestler, E. J. (2011) · Frontiers in Neuroanatomy · doi:10.3389/fnana.2011.00041 · Cited by 371 · see citing works
Distinct Roles of GABAergic Interneurons in the Regulation of Striatal Output Pathways
Gittis, A. H., Nelson, A., Thwin, M. T., Palop, J. J., & Kreitzer, A. C. (2010) · Journal of Neuroscience · doi:10.1523/jneurosci.4870-09.2010 · Cited by 364 · see citing works
Self-citationThe basal ganglia in Parkinson's disease: Current concepts and unexplained observations
Obeso, J. A., Marin, C., Rodriguez-Oroz, C., Blesa, J., Benitez-Temiño, B., Mena-Segovia, J., Rodríguez, M., & Olanow, C. W. (2009) · Annals of Neurology · doi:10.1002/ana.21481 · Cited by 359 · see citing works
Postsynaptic TRPV1 triggers cell type–specific long-term depression in the nucleus accumbens
Grueter, B. A., Brasnjo, G., & Malenka, R. C. (2010) · Nature Neuroscience · doi:10.1038/nn.2685 · Cited by 353 · see citing works
Self-citationDeep Brain Stimulation for Neurologic and Neuropsychiatric Disorders
Wichmann, T., & DeLong, M. R. (2006) · Neuron · doi:10.1016/j.neuron.2006.09.022 · Cited by 331 · see citing works
Raymond, L. A., André, V. M., Cepeda, C., Gladding, C. M., Milnerwood, A. J., & Levine, M. S. (2011) · Neuroscience · doi:10.1016/j.neuroscience.2011.08.052 · Cited by 319 · see citing works
Cannabis, the mind and society: the hash realities
Murray, R. M., Morrison, P. D., Henquet, C., & Forti, M. D. (2007) · Nature reviews. Neuroscience · doi:10.1038/nrn2253 · Cited by 319 · see citing works
Circuit-specific signaling in astrocyte-neuron networks in basal ganglia pathways
Martín, R., Bajo-Grañeras, R., Moratalla, R., Perea, G., & Araque, A. (2015) · Science · doi:10.1126/science.aaa7945 · Cited by 312 · see citing works
D2R striatopallidal neurons inhibit both locomotor and drug reward processes
Durieux, P. F., Bearzatto, B., Guiducci, S., Buch, T., Waisman, A., Zoli, M., Schiffmann, S. N., & de Kerchove d'Exaerde, A. (2009) · Nature Neuroscience · doi:10.1038/nn.2286 · Cited by 297 · see citing works
Fieblinger, T., Graves, S. M., Sebel, L. E., Alcacer, C., Plotkin, J. L., Gertler, T. S., Chan, C. S., Heiman, M., Greengard, P., Cenci, M. A., et al. (2014) · Nature Communications · doi:10.1038/ncomms6316 · Cited by 293 · see citing works
Corticostriatal and Thalamostriatal Synapses Have Distinctive Properties
Ding, J., Peterson, J. D., & Surmeier, D. J. (2008) · Journal of Neuroscience · doi:10.1523/jneurosci.0435-08.2008 · Cited by 288 · see citing works
Short latency cerebellar modulation of the basal ganglia
Chen, C. H., Fremont, R., Arteaga-Bracho, E. E., & Khodakhah, K. (2014) · Nature Neuroscience · doi:10.1038/nn.3868 · Cited by 286 · see citing works
Acetylcholine–dopamine balance hypothesis in the striatum: An update
Aosaki, T., Miura, M., Suzuki, T., Nishimura, K., & Masuda, M. (2010) · Geriatrics and gerontology international/Geriatrics & gerontology international · doi:10.1111/j.1447-0594.2010.00588.x · Cited by 276 · see citing works
Matamales, M., Bertran‐Gonzalez, J., Salomon, L., Degos, B., Deniau, J., Valjent, E., Hervé, D., & Girault, J. (2009) · PLoS ONE · doi:10.1371/journal.pone.0004770 · Cited by 275 · see citing works
Smith, R. J., Lobo, M. K., Spencer, S., & Kalivas, P. W. (2013) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2013.01.026 · Cited by 272 · see citing works
Competitive regulation of synaptic Ca2+ influx by D2 dopamine and A2A adenosine receptors
Higley, M. J., & Sabatini, B. L. (2010) · Nature Neuroscience · doi:10.1038/nn.2592 · Cited by 271 · see citing works
The Role of Lipids in Parkinson’s Disease
Xicoy, H., Wieringa, B., & Martens, G. J. M. (2019) · Cells · doi:10.3390/cells8010027 · Cited by 255 · see citing works
Seven problems on the basal ganglia
Nambu, A. (2008) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2008.11.001 · Cited by 252 · see citing works
Portmann, T., Yang, M., Mao, R., Panagiotakos, G., Ellegood, J., Dolen, G., Bader, P. L., Grueter, B. A., Goold, C., Fisher, E., et al. (2014) · Cell Reports · doi:10.1016/j.celrep.2014.03.036 · Cited by 245 · see citing works
Self-citationGenetic Dissection of Behavioural and Autonomic Effects of Δ9-Tetrahydrocannabinol in Mice
Monory, K., Blaudzun, H., Massa, F., Kaiser, N., Lemberger, T., Schütz, G., Wotjak, C. T., Lutz, B., & Marsicano, G. (2007) · PLoS Biology · doi:10.1371/journal.pbio.0050269 · Cited by 241 · see citing works
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 241 · see citing works
Synaptic functions of endocannabinoid signaling in health and disease
Araque, A., Castillo, P. E., Manzoni, O. J., & Tonini, R. (2017) · Neuropharmacology · doi:10.1016/j.neuropharm.2017.06.017 · Cited by 239 · see citing works
Neurocomputational models of basal ganglia function in learning, memory and choice
Cohen, M. X., & Frank, M. J. (2008) · Behavioural Brain Research · doi:10.1016/j.bbr.2008.09.029 · Cited by 238 · see citing works
Shuen, J. A., Chen, M., Gloss, B. R., & Calakos, N. (2008) · Journal of Neuroscience · doi:10.1523/jneurosci.5492-07.2008 · Cited by 231 · see citing works
Price, D. A., Martinez, A. A., Seillier, A., Koek, W., Acosta, Y. P. V., Fernández, E., Strong, R., Lutz, B., Marsicano, G., Roberts, J. L., et al. (2009) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2009.06764.x · Cited by 231 · see citing works
Doig, N. M., Moss, J., & Bolam, J. P. (2010) · Journal of Neuroscience · doi:10.1523/jneurosci.1623-10.2010 · Cited by 230 · see citing works
Cannabinoids in health and disease
Kogan, N. M., & Mechoulam, R. (2007) · Dialogues in Clinical Neuroscience · doi:10.31887/dcns.2007.9.4/nkogan · Cited by 227 · see citing works
Advances in the pharmacological treatment of Parkinson's disease: targeting neurotransmitter systems
Brichta, L., Greengard, P., & Flajolet, M. (2013) · Trends in Neurosciences · doi:10.1016/j.tins.2013.06.003 · Cited by 224 · see citing works
Shen, C.-J., Zheng, D., Li, K., Yang, J., Pan, H., Yu, X.-D., Fu, J., Zhu, Y., Sun, Q.-X., Tang, M., et al. (2019) · Nature Medicine · doi:10.1038/s41591-018-0299-9 · Cited by 223 · see citing works
The endocannabinoid system as a target for the treatment of motor dysfunction
Fernández‐Ruíz, J. (2009) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2008.00088.x · Cited by 218 · see citing works
Paparelli, A., di Forti, M., Morrison, P., & Murray, R. (2010) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2011.00001 · Cited by 176 · see citing works
Endocannabinoid system in neurodegenerative disorders
Basavarajappa, B. S., Shivakumar, M., Joshi, V., & Subbanna, S. (2017) · Journal of Neurochemistry · doi:10.1111/jnc.14098 · Cited by 212 · see citing works
Ahn, K., Johnson, D. S., & Cravatt, B. F. (2009) · Expert Opinion on Drug Discovery · doi:10.1517/17460440903018857 · Cited by 198 · see citing works
Szutorisz, H., DiNieri, J. A., Sweet, E. S., Egervári, G., Michaelides, M., Carter, J. M., Ren, Y., Miller, M. L., Blitzer, R. D., & Hurd, Y. L. (2014) · Neuropsychopharmacology · doi:10.1038/npp.2013.352 · Cited by 197 · see citing works
Corticostriatal projection neurons – dichotomous types and dichotomous functions
Reiner, A. J. (2010) · Frontiers in Neuroanatomy · doi:10.3389/fnana.2010.00142 · Cited by 196 · see citing works
Milestones in research on the pathophysiology of Parkinson's disease
Wichmann, T., DeLong, M. R., Guridi, J., & Obeso, J. A. (2011) · Movement Disorders · doi:10.1002/mds.23695 · Cited by 196 · see citing works
Morgese, M. G., Cassano, T., Cuomo, V., & Giuffrida, A. (2007) · Experimental Neurology · doi:10.1016/j.expneurol.2007.07.021 · Cited by 195 · see citing works
Cepeda, C., André, V. M., Yamazaki, I., Wu, N., Max Kleiman-weiner, A., & Levine, M. S. (2008) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2008.06038.x · Cited by 195 · see citing works
Russo, E. B. (2016) · Cannabis and Cannabinoid Research · doi:10.1089/can.2016.0009 · Cited by 193 · see citing works
The major central endocannabinoid directly acts at GABA A receptors
Sigel, E., Baur, R., Rácz, I., Marazzi, J., Smart, T. G., Zimmer, A., & Gertsch, J. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1113444108 · Cited by 187 · see citing works
Lerner, T. N., & Kreitzer, A. C. (2012) · Neuron · doi:10.1016/j.neuron.2011.11.015 · Cited by 185 · see citing works
Self-citationDopamine and synaptic plasticity in dorsal striatal circuits controlling action selection
Surmeier, D. J., Plotkin, J. L., & Shen, W. (2009) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2009.10.003 · Cited by 183 · see citing works
The endocannabinoid system as a target for the treatment of neurodegenerative disease
Scotter, E. L., Abood, M. E., & Glass, M. (2010) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2010.00735.x · Cited by 181 · see citing works
A fluorescent sensor for spatiotemporally resolved imaging of endocannabinoid dynamics in vivo
Dong, A., He, K., Dudok, B., Farrell, J. S., Guan, W., Liput, D. J., Puhl, H. L., Cai, R., Wang, H., Duan, J., et al. (2021) · Nature Biotechnology · doi:10.1038/s41587-021-01074-4 · Cited by 179 · see citing works
Distribution of the Endocannabinoid System in the Central Nervous System
Hu, S. S., & Mackie, K. (2015) · Handbook of experimental pharmacology · doi:10.1007/978-3-319-20825-1_3 · Cited by 177 · see citing works
Acute and chronic effects of ethanol on learning-related synaptic plasticity
Zorumski, C. F., Mennerick, S. J., & Izumi, Y. (2013) · Alcohol · doi:10.1016/j.alcohol.2013.09.045 · Cited by 177 · see citing works
Striatopallidal dysfunction underlies repetitive behavior in Shank3-deficient model of autism
Wang, W., Li, C., Chen, Q., van der Goes, M.-S. H., Hawrot, J., Yao, A. Y., Gao, X., Lu, C., Zang, Y., Zhang, Q., et al. (2017) · Journal of Clinical Investigation · doi:10.1172/jci87997 · Cited by 177 · see citing works
Rapid Target-Specific Remodeling of Fast-Spiking Inhibitory Circuits after Loss of Dopamine
Gittis, A. H., Hang, G. B., LaDow, E., Shoenfeld, L. R., Atallah, B. V., Finkbeiner, S. M., & Kreitzer, A. C. (2011) · Neuron · doi:10.1016/j.neuron.2011.06.035 · Cited by 176 · see citing works
Self-citationAde, K. K., Wan, Y., Chen, M., Gloss, B. R., & Calakos, N. (2011) · Frontiers in Systems Neuroscience · doi:10.3389/fnsys.2011.00032 · Cited by 175 · see citing works
Dopamine imbalance in Huntington's disease: a mechanism for the lack of behavioral flexibility
Chen, J., Wang, E. A., Cepeda, C., & Levine, M. S. (2013) · Frontiers in Neuroscience · doi:10.3389/fnins.2013.00114 · Cited by 175 · see citing works
Monday, H. R., Younts, T. J., & Castillo, P. E. (2018) · Annual Review of Neuroscience · doi:10.1146/annurev-neuro-080317-062155 · Cited by 175 · see citing works
Reversing cocaine-induced synaptic potentiation provides enduring protection from relapse
Moussawi, K., Zhou, W., Shen, H., Reichel, C. M., See, R. E., Carr, D. B., & Kalivas, P. W. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1011265108 · Cited by 174 · see citing works
What is the degree of segregation between striatonigral and striatopallidal projections?
Bertran‐Gonzalez, J. (2010) · Frontiers in Neuroanatomy · doi:10.3389/fnana.2010.00136 · Cited by 173 · see citing works
Presynaptic LTP and LTD of Excitatory and Inhibitory SynapsesPreprint
Castillo, P. E. (2011) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a005728 · Cited by 169 · see citing works
Paillé, V., Picconi, B., Bagetta, V., Ghiglieri, V., Sgobio, C., Filippo, M. D., Viscomi, M. T., Giampà, C., Fusco, F. R., Gardoni, F., et al. (2010) · Journal of Neuroscience · doi:10.1523/jneurosci.2149-10.2010 · Cited by 168 · see citing works
Joshi, P. R., Wu, N.-P., André, V. M., Cummings, D. M., Cepeda, C., Joyce, J. A., Carroll, J. B., Leavitt, B. R., Hayden, M. R., Levine, M. S., et al. (2009) · Journal of Neuroscience · doi:10.1523/jneurosci.5687-08.2009 · Cited by 166 · see citing works
Differential Tonic GABA Conductances in Striatal Medium Spiny Neurons
Ade, K. K., Janssen, M. J., Ortinski, P. I., & Vicini, S. (2008) · Journal of Neuroscience · doi:10.1523/jneurosci.3908-07.2008 · Cited by 164 · see citing works
Striatal synapses, circuits, and Parkinson's disease
Zhai, S., Tanimura, A., Graves, S. M., Shen, W., & Surmeier, D. J. (2017) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2017.08.004 · Cited by 164 · see citing works
Cannabinoid–Dopamine Interaction in the Pathophysiology and Treatment of CNS Disorders
Fernández‐Ruíz, J., Hernández, M., & Ramos, J. A. (2010) · CNS Neuroscience & Therapeutics · doi:10.1111/j.1755-5949.2010.00144.x · Cited by 163 · see citing works
Di Filippo, M., Picconi, B., Tantucci, M., Ghiglieri, V., Bagetta, V., Sgobio, C., Tozzi, A., Parnetti, L., & Calabresi, P. (2009) · Behavioural Brain Research · doi:10.1016/j.bbr.2008.09.025 · Cited by 158 · see citing works
Dopaminergic modulation of striatal networks in health and Parkinson's disease
Surmeier, D. J., Graves, S. M., & Shen, W. (2014) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2014.07.008 · Cited by 154 · see citing works
Muscarinic modulation of striatal function and circuitry
Goldberg, J. A., Ding, J. B., & Surmeier, D. J. (2012) · Handbook of Experimental Pharmacology · doi:10.1007/978-3-642-23274-9_10 · Cited by 150 · see citing works
Extrastriatal dopaminergic circuits of the basal ganglia
Rommelfanger, K. S. (2010) · Frontiers in Neuroanatomy · doi:10.3389/fnana.2010.00139 · Cited by 150 · see citing works
Tozzi, A., de Iure, A., Filippo, M. D., Tantucci, M., Costa, C., Borsini, F., Ghiglieri, V., Giampà, C., Fusco, F. R., Picconi, B., et al. (2011) · Journal of Neuroscience · doi:10.1523/jneurosci.4082-10.2011 · Cited by 148 · see citing works
Promising cannabinoid-based therapies for Parkinson’s disease: motor symptoms to neuroprotection
More, S. V., & Choi, D. (2015) · Molecular Neurodegeneration · doi:10.1186/s13024-015-0012-0 · Cited by 145 · see citing works
- Authors
- Kreitzer, A. C., & Malenka, R. C.
- Affiliations
- Stanford Medicine (US)
- Corresponding author
- Malenka, Robert C.
- Venue
- Nature
- Published
- 2007-02
- Volume
- 445
- Issue
- 7128
- Pages
- 643-647
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2003314029
- Cited by
- 735
- References
- 35
- Citations by year
- 2026: 12 · 2025: 21 · 2024: 21 · 2023: 17 · 2022: 17 · 2021: 34 · 2020: 28 · 2019: 41 · 2018: 41 · 2017: 45 · 2016: 37 · 2015: 34 · 2014: 37 · 2013: 31 · 2012: 47
- FWCI
- 44.31
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Topics
- Health Sciences › Medicine › Pharmacology › Cannabis and Cannabinoid Research
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- striatum, indirect pathway, direct pathway, medium spiny neurons, dopamine D2 receptor, basal ganglia, motor impairment, synaptic plasticity, NMDA receptor currents, release probability, transgenic mouse model, therapeutic target, Huntington's disease, substantia nigra pars reticulata
- MeSH terms
- Animals, Benzamides, Carbamates, Disease Models, Animal, Dopamine, Mice, Transgenic, Morpholines, Naphthalenes, Neuronal Plasticity, Parkinson Disease, Piperidines, Psychomotor Performance, Pyrazoles, Reserpine, Synapses, Receptors, N-Methyl-D-Aspartate, Oxidopamine, Neostriatum, Receptors, Dopamine D2, Excitatory Postsynaptic Potentials, Long-Term Synaptic Depression, Receptor, Cannabinoid, CB1, Benzoxazines, Mice, Cannabinoid Receptor Modulators, Endocannabinoids, Dopamine D2 Receptor Antagonists, In Vitro Techniques
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