The DOI matches its Crossref record; 28 of the 28 references it cites were found in a registry or an index.
Regulation of parkinsonian motor behaviours by optogenetic control of basal ganglia circuitry
Open accessAbstract
Neural circuits of the basal ganglia are critical for motor planning and action selection. Two parallel basal ganglia pathways have been described, and have been proposed to exert opposing influences on motor function. According to this classical model, activation of the 'direct' pathway facilitates movement and activation of the 'indirect' pathway inhibits movement. However, more recent anatomical and functional evidence has called into question the validity of this hypothesis. Because this model has never been empirically tested, the specific function of these circuits in behaving animals remains unknown. Here we report direct activation of basal ganglia circuitry in vivo, using optogenetic control of direct- and indirect-pathway medium spiny projection neurons (MSNs), achieved through Cre-dependent viral expression of channelrhodopsin-2 in the striatum of bacterial artificial chromosome transgenic mice expressing Cre recombinase under control of regulatory elements for the dopamine D1 or D2 receptor. Bilateral excitation of indirect-pathway MSNs elicited a parkinsonian state, distinguished by increased freezing, bradykinesia and decreased locomotor initiations. In contrast, activation of direct-pathway MSNs reduced freezing and increased locomotion. In a mouse model of Parkinson's disease, direct-pathway activation completely rescued deficits in freezing, bradykinesia and locomotor initiation. Taken together, our findings establish a critical role for basal ganglia circuitry in the bidirectional regulation of motor behaviour and indicate that modulation of direct-pathway circuitry may represent an effective therapeutic strategy for ameliorating parkinsonian motor deficits.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
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?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“the insula allocates over one-third of its projection to the striatum, particularly the dorsal region, underscoring its pivotal role in motor control and action selection [21][22][23][24].”
From The Insular Cortex: An Interface Between Sensation, Emotion and Cognition (2024) · cites this paper as [21]
Experimental — accuracy not yet measuredIn the citing paper
“In a simplified framework, these anatomically distinct pathways have been thought to oppose each other, resulting in net inhibition of thalamus and decrease of movement via activation of the indirect pathway, or net disinhibition (i.e. overall excitation) and increase of movement by activation of the direct pathway (Fig.1) 46,47.”
From DISSECTING OCD CIRCUITS: FROM ANIMAL MODELS TO TARGETED TREATMENTS: Review: Dissecting OCD Circuits: Animals to Treatments (2015) · cites this paper as [46]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
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
Millisecond-timescale, genetically targeted optical control of neural activity
Boyden, E. S., Zhang, F., Bamberg, E., Nagel, G., & Deisseroth, K. A. (2005) · Nature Neuroscience · doi:10.1038/nn1525 · Cited by 5,015
Self-citationFunctional 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
Primate models of movement disorders of basal ganglia origin
DeLong, M. R. (1990) · Trends in Neurosciences · doi:10.1016/0166-2236(90)90110-v · Cited by 3,824
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
Parvalbumin neurons and gamma rhythms enhance cortical circuit performance
Sohal, V. S., Zhang, F., Yizhar, O., & Deisseroth, K. (2009) · Nature · doi:10.1038/nature07991 · Cited by 2,606
Self-citationDriving fast-spiking cells induces gamma rhythm and controls sensory responses
Cardin, J. A., Carlén, M., Meletis, K., Knoblich, U., Zhang, F., Deisseroth, K., Tsai, L.-H., & Moore, C. I. (2009) · Nature · doi:10.1038/nature08002 · Cited by 2,603
Self-citationThe role of the basal ganglia in habit formation
Yin, H. H., & Knowlton, B. J. (2006) · Nature Reviews Neuroscience · doi:10.1038/nrn1919 · Cited by 2,402
Reversal of experimental parkinsonism by lesions of the subthalamic nucleus.
Bergman, H., Wichmann, T., & Delong, M. (1990) · Science · doi:10.1126/science.2402638 · Cited by 2,003
The primate subthalamic nucleus. II. Neuronal activity in the MPTP model of parkinsonism
Bergman, H., Wichmann, T., Karmon, B., & DeLong, M. R. (1994) · Journal of Neurophysiology · doi:10.1152/jn.1994.72.2.507 · Cited by 1,366
Neural substrates of awakening probed with optogenetic control of hypocretin neurons
Adamantidis, A. R., Zhang, F., Aravanis, A. M., Deisseroth, K., & de Lecea, L. (2007) · Nature · doi:10.1038/nature06310 · Cited by 1,341
Self-citationRole of the Basal Ganglia in the Control of Purposive Saccadic Eye Movements
Hikosaka, O., Takikawa, Y., & Kawagoe, R. (2000) · Physiological Reviews · doi:10.1152/physrev.2000.80.3.953 · Cited by 1,334
The Basal Ganglia and Adaptive Motor Control
Graybiel, A. M., Aosaki, T., Flaherty, A. W., & Kimura, M. (1994) · Science · doi:10.1126/science.8091209 · Cited by 1,324
Gong, S., Doughty, M., Harbaugh, C. R., Cummins, A., Hatten, M. E., Heintz, N., & Gerfen, C. R. (2007) · The Journal of Neuroscience · doi:10.1523/jneurosci.2707-07.2007 · Cited by 977
Smith, Y., Bevan, M. D., Shink, É., & Bolam, J. P. (1998) · Neuroscience · doi:10.1016/s0306-4522(98)00004-9 · Cited by 961
Arenkiel, B. R., Peca, J., Davison, I. G., Feliciano, C., Deisseroth, K., Augustine, G. J., Ehlers, M. D., & Feng, G. (2007) · Neuron · doi:10.1016/j.neuron.2007.03.005 · Cited by 755
Self-citationEndocannabinoid-mediated rescue of striatal LTD and motor deficits in Parkinson's disease models
Kreitzer, A. C., & Malenka, R. C. (2007) · Nature · doi:10.1038/nature05506 · Cited by 735
Self-citationProjection subtypes of rat neostriatal matrix cells revealed by intracellular injection of biocytin
Kawaguchi, Y., Wilson, C. J., & Emson, P. C. (1990) · Journal of Neuroscience · doi:10.1523/jneurosci.10-10-03421.1990 · Cited by 569
Sparse optical microstimulation in barrel cortex drives learned behaviour in freely moving mice
Huber, D., Petreanu, L., Ghitani, N., Ranade, S., Hromádka, T., Mainen, Z., & Svoboda, K. (2008) · Nature · doi:10.1038/nature06445 · Cited by 539
Physiology and pharmacology of striatal neurons
Kreitzer, A. C. (2009) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.051508.135422 · Cited by 530
Self-citationFunctional diversity and specificity of neostriatal interneurons
Tepper, J. M., & Bolam, J. P. (2004) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2004.10.003 · Cited by 526
Targeting and Readout Strategies for Fast Optical Neural ControlIn VitroandIn Vivo
Gradinaru, V., Thompson, K. R., Zhang, F., Mogri, M., Kay, K., Schneider, M. B., & Deisseroth, K. A. (2007) · Journal of Neuroscience · doi:10.1523/jneurosci.3578-07.2007 · Cited by 482
Self-citationMallet, N. P., Ballion, B., Moine, C. L., & Gonon, F. (2006) · Journal of Neuroscience · doi:10.1523/jneurosci.4439-05.2006 · Cited by 413
Schwarting, R. K. W., & Huston, J. P. (1996) · Progress in Neurobiology · doi:10.1016/s0301-0082(96)00015-9 · Cited by 356
Behavioural assessment of mice lacking D1A dopamine receptors
Smith, D., Striplin, C. D., Geller, A. M., Mailman, R. B., Drago, J., Lawler, C. P., & Gallagher, M. (1998) · Neuroscience · doi:10.1016/s0306-4522(97)00608-8 · Cited by 334
Oscillations in the basal ganglia under normal conditions and in movement disorders
Gatev, P., Darbin, O., & Wichmann, T. (2006) · Movement Disorders · doi:10.1002/mds.21033 · Cited by 327
Quantitative immunocytochemistry of DARPP-32-expressing neurons in the rat caudatoputamen
Ouimet, C. C., Langley-Gullion, K. C., & Greengard, P. (1998) · Brain Research · doi:10.1016/s0006-8993(98)00724-0 · Cited by 165
Autonomous pacemakers in the basal ganglia: who needs excitatory synapses anyway?
Surmeier, D. J., Mercer, J. N., & Chan, C. S. (2005) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2005.05.007 · Cited by 128
Flagged first, then by citations
Cited by
Sorted by citations
The physiology, signaling, and pharmacology of dopamine receptors
Beaulieu, J.-M., & Gainetdinov, R. R. (2011) · Pharmacological Reviews · doi:10.1124/pr.110.002642 · Cited by 2,763
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
Optogenetics in neural systems
Yizhar, O., Fenno, L. E., Davidson, T. J., Mogri, M., & Deisseroth, K. (2011) · Neuron · doi:10.1016/j.neuron.2011.06.004 · Cited by 1,881
Self-citationMolecular diversity and specializations among the cells of the adult mouse brain
Saunders, A., Macosko, E. Z., Wysoker, A., Goldman, M., Krienen, F. M., de Rivera, H., Bien, E., Baum, M., Bortolin, L., Wang, S., et al. (2018) · Cell · doi:10.1016/j.cell.2018.07.028 · Cited by 1,531
The development and application of optogenetics
Fenno, L., Yizhar, O., & Deisseroth, K. (2011) · Annual Review of Neuroscience · doi:10.1146/annurev-neuro-061010-113817 · Cited by 1,822
Self-citation
Metadata
- Authors
- Kravitz, A. V., Freeze, B. S., Parker, P. R. L., Kay, K., Thwin, M. T., Deisseroth, K., & Kreitzer, A. C.
- Affiliations
- Gladstone Institutes (US)
- Stanford University (US)
- Corresponding author
- Kreitzer, Anatol C.
- ORCID
- Venue
- Nature
- Published
- 2010-07
- Volume
- 466
- Issue
- 7306
- Pages
- 622-626
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC3552484
- OpenAlex
- W1971797700
- Cited by
- 1,885
- References
- 28
- Citations by year
- 2026: 76 · 2025: 110 · 2024: 138 · 2023: 110 · 2022: 96 · 2021: 120 · 2020: 118 · 2019: 119 · 2018: 137 · 2017: 133 · 2016: 128 · 2015: 138 · 2014: 133 · 2013: 112 · 2012: 100
- FWCI
- 62.12
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- W. M. Keck Foundation
- McKnight Foundation
- National Institutes of Health
- University of California, San Francisco
- National Institute of Neurological Disorders and Stroke (R01NS064984)
- Topics
- Health Sciences › Medicine › Clinical Neurology › Deep Brain Stimulation and Movement Disorders
- Health Sciences › Medicine › Clinical Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Neuroscience › Cognitive Neuroscience › Motor Control and Adaptation
- Keywords
- basal ganglia, Parkinson's disease, direct pathway, indirect pathway, medium spiny neurons, striatum, optogenetics, channelrhodopsin-2, dopamine D1 receptor, dopamine D2 receptor, locomotion, bradykinesia, freezing behavior, motor control, functional connectivity, mouse model of Parkinson's disease, viral gene expression, Cre recombinase
- MeSH terms
- Channelrhodopsins, Animals, Basal Ganglia, Disease Models, Animal, Gait, Mice, Transgenic, Models, Neurological, Motor Activity, Neural Pathways, Neurons, Parkinson Disease, Psychomotor Performance, Receptors, Dopamine, Oxidopamine, Neostriatum, Hypokinesia, Integrases, Chromosomes, Artificial, Bacterial, 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
