Insulin receptor signaling regulates synapse number, dendritic plasticity, and circuit function in vivo
Open accessAbstract
Insulin receptor signaling has been postulated to play a role in synaptic plasticity; however, the function of the insulin receptor in CNS is not clear. To test whether insulin receptor signaling affects visual system function, we recorded light-evoked responses in optic tectal neurons in living Xenopus tadpoles. Tectal neurons transfected with dominant-negative insulin receptor (dnIR), which reduces insulin receptor phosphorylation, or morpholino against insulin receptor, which reduces total insulin receptor protein level, have significantly smaller light-evoked responses than controls. dnIR-expressing neurons have reduced synapse density as assessed by EM, decreased AMPA mEPSC frequency, and altered experience-dependent dendritic arbor structural plasticity, although synaptic vesicle release probability, assessed by paired-pulse responses, synapse maturation, assessed by AMPA/NMDA ratio and ultrastructural criteria, are unaffected by dnIR expression. These data indicate that insulin receptor signaling regulates circuit function and plasticity by controlling synapse density.
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Neuronal insulin receptors are involved in diverse brain functions including synapse plasticity, learning and memory.
“Neuronal IRs are involved in diverse brain functions including synapse plasticity, learning and memory (Chiu et al., 2008; Craft et al., 1996; Kern et al., 2001; Lee et al., 2005; Park et al., 2000).”
From The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer’s disease (2011) · cites this paper as Chiu et al., 2008
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Cites
Normal Table of Xenopus Laevis (Daudin)
Nieuwkoop, P. D., & Faber, J. (1958) · Copeia · doi:10.2307/1439568 · Cited by 4,542 · see citing works
Normal table of Xenopus laevis (Daudin)
Gurdon, J. B. (1995) · Trends in Genetics · doi:10.1016/s0168-9525(00)89129-5 · Cited by 2,888 · see citing works
Long-term in vivo imaging of experience-dependent synaptic plasticity in adult cortex
Trachtenberg, J. T., Chen, B. E., Knott, G. W., Feng, G., Sanes, J. R., Welker, E., & Svoboda, K. (2002) · Nature · doi:10.1038/nature01273 · Cited by 1,927 · see citing works
Insulin receptors are widely distributed in the central nervous system of the rat
Havránková, J., Roth, J., & Brownstein, M. (1978) · Nature · doi:10.1038/272827a0 · Cited by 1,116 · see citing works
Regulation of AMPA receptor endocytosis by a signaling mechanism shared with LTD
Beattie, E. C., Carroll, R. C., Yu, X., Morishita, W., Yasuda, H., von Zastrow, M., & Malenka, R. C. (2000) · Nature Neuroscience · doi:10.1038/81823 · Cited by 745 · see citing works
Insulin signaling in health and disease
White, M. F. (2003) · Science · doi:10.1126/science.1092952 · Cited by 733 · cited 1× · see citing works
“The insulin receptor requires the formation of a disulfide-linked dimer to be a functional receptor (White, 2003).”
Man, H., Lin, J., Ju, W. H., Ahmadian, G., Liu, L., Becker, L. E., Sheng, M., & Wang, Y. T. (2000) · Neuron · doi:10.1016/s0896-6273(00)81067-3 · Cited by 698 · see citing works
Subunit-specific temporal and spatial patterns of AMPA receptor exocytosis in hippocampal neurons
Passafaro, M., Piëch, V., & Sheng, M. (2001) · Nature Neuroscience · doi:10.1038/nn0901-917 · Cited by 655 · see citing works
IRSp53 is an essential intermediate between Rac and WAVE in the regulation of membrane ruffling
Miki, H., Yamaguchi, H., Suetsugu, S., & Takenawa, T. (2000) · Nature · doi:10.1038/35047107 · Cited by 557 · see citing works
Maturation of a Central Glutamatergic Synapse
Wu, G.-Y., Malinow, R., & Cline, H. T. (1996) · Science · doi:10.1126/science.274.5289.972 · Cited by 546 · see citing works
Self-citationRecruitment of functional GABAA receptors to postsynaptic domains by insulin
Wan, Q., Xiong, Z., Man, H., Ackerley, C., Braunton, J., Lu, W. Y., Becker, L. E., MacDonald, J. F., & Wang, Y. T. (1997) · Nature · doi:10.1038/41792 · Cited by 537 · see citing works
Brain Insulin Receptors and Spatial Memory
Zhao, W., Chen, H., Xu, H., Moore, E., Meiri, N., Quon, M. J., & Alkon, D. L. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.49.34893 · Cited by 535 · see citing works
In vivo imaging of synapse formation on a growing dendritic arbor
Niell, C. M., Meyer, M. P., & Smith, S. J. (2004) · Nature Neuroscience · doi:10.1038/nn1191 · Cited by 441 · see citing works
Dendrite growth increased by visual activity requires NMDA receptor and Rho GTPases
Sin, W. C., Haas, K. Z., Ruthazer, E. S., & Cline, H. T. (2002) · Nature · doi:10.1038/nature00987 · Cited by 433 · see citing works
Self-citationCdc42 induces filopodia by promoting the formation of an IRSp53:Mena complex
Vermeren, S., Jordens, I., Gevaert, K., Driessens, M. H. E., Vandekerckhove, J. S., & Hall, A. (2001) · Current Biology · doi:10.1016/s0960-9822(01)00506-1 · Cited by 420 · see citing works
Ebina, Y., Araki, E., Taira, M., Shimada, F., Mori, M., Craik, C. S., Siddle, K., Pierce, S. B., Roth, R. A., & Rutter, W. J. (1987) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.84.3.704 · Cited by 390 · see citing works
Abbott, M.-A., Wells, D. G., & Fallon, J. R. (1999) · The Journal of Neuroscience · doi:10.1523/jneurosci.19-17-07300.1999 · Cited by 327 · see citing works
Skeberdis, V. A., Lan, J.-Y., Zheng, X., Zukin, R. S., & Bennett, M. V. L. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.051634698 · Cited by 303 · see citing works
Ahmadian, G., Ju, W., Liu, L., Wyszynski, M., Lee, S. H., Dunah, A. W., Taghibiglou, C., Wang, Y., Lu, J., Wong, T. P., et al. (2004) · The EMBO Journal · doi:10.1038/sj.emboj.7600126 · Cited by 296 · see citing works
Distribution of insulin receptor-like immunoreactivity in the rat forebrain
Unger, J. W., McNeill, T. H., Moxley, R. T., White, M. F., Moss, A., & Livingston, J. N. (1989) · Neuroscience · doi:10.1016/0306-4522(89)90036-5 · Cited by 294 · see citing works
Choi, J., Ko, J., Rácz, B., Burette, A., Lee, J.-R., Kim, S.-H., Na, M., Lee, H. W., Kim, K., Weinberg, R. J., et al. (2005) · Journal of Neuroscience · doi:10.1523/jneurosci.3212-04.2005 · Cited by 224 · see citing works
Insulin receptor signaling in long-term memory consolidation following spatial learningPreprint
Dou, J., Chen, M., Dufour, F., Alkon, D. L., & Zhao, W. (2005) · Learning & Memory · doi:10.1101/lm.88005 · Cited by 217 · see citing works
Lee, C.-C., Huang, C., Wu, M.-Y., & Hsu, K. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m414112200 · Cited by 199 · see citing works
Akerman, C. J., & Cline, H. T. (2006) · Journal of Neuroscience · doi:10.1523/jneurosci.0319-06.2006 · Cited by 189 · see citing works
Self-citationAMPA receptors regulate experience-dependent dendritic arbor growth <i>in</i> <i>vivo</i>
Haas, K., Li, J., & Cline, H. T. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0602670103 · Cited by 174 · see citing works
Self-citationInsulin Is Released from Rat Brain Neuronal Cells in Culture
Clarke, D. W., Mudd, L. M., Boyd, F. T., Fields, M. J., & Raizada, M. K. (1986) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1986.tb00686.x · Cited by 173 · see citing works
Targeted electroporation in Xenopus tadpoles in vivo – from single cells to the entire brain
Haas, K. Z., Jensen, K., Sin, W. C., et al. (2002) · Differentiation · doi:10.1046/j.1432-0436.2002.700404.x · Cited by 164 · see citing works
Govind, S., Kozma, R., Monfries, C. A. L., Lim, L., & Ahmed, S. (2001) · The Journal of Cell Biology · doi:10.1083/jcb.152.3.579 · Cited by 162 · see citing works
Axons Guided by Insulin Receptor in Drosophila Visual System
Song, J., Wu, L., Chen, Z., Kohanski, R. A., & Pick, L. (2003) · Science · doi:10.1126/science.1081203 · Cited by 146 · see citing works
Moving visual stimuli rapidly induce direction sensitivity of developing tectal neurons
Engert, F., Tao, H. W., Zhang, L. I., & Poo, M. (2002) · Nature · doi:10.1038/nature00988 · Cited by 144 · see citing works
Visual input induces long-term potentiation of developing retinotectal synapses
Zhang, L. I., Tao, H. W., & Poo, M. (2000) · Nature Neuroscience · doi:10.1038/76665 · Cited by 124 · see citing works
Presynaptic Modulation of the Retinogeniculate Synapse
Chen, C., & Regehr, W. G. (2003) · Journal of Neuroscience · doi:10.1523/jneurosci.23-08-03130.2003 · Cited by 107 · see citing works
Self-citationThe Insulin Receptor Substrate IRSp53 Links Postsynaptic shank1 to the Small G-Protein cdc42
Soltau, M. (2002) · Molecular and Cellular Neuroscience · doi:10.1006/mcne.2002.1201 · Cited by 96 · see citing works
In vivo single-cell electroporation for transfer of DNA and macromolecules
Bestman, J. E., Ewald, R. C., Chiu, S., et al. (2006) · Nature Protocols · doi:10.1038/nprot.2006.186 · Cited by 92 · see citing works
Self-citationBDNF increases synapse density in dendrites of developing tectal neurons in vivo
Sanchez, A. L., Matthews, B. J., Meynard, M. M., Hu, B., Javed, S., & Cohen‐Cory, S. (2006) · Development · doi:10.1242/dev.02409 · Cited by 87 · see citing works
Enhanced visual activity in vivo forms nascent synapses in the developing retinotectal projection.
Aizenman, C. D., & Cline, H. (2007) · Journal of Neurophysiology · doi:10.1152/jn.00452.2006 · Cited by 71 · see citing works
Self-citationValenciano, A. I., Corrochano, S., de Pablo, F., de la Villa, P., & de la Rosa, E. J. (2006) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2006.04043.x · Cited by 55 · see citing works
The insulin receptor activation process involves localized conformational changes
Baron, V. T., Kaliman, P., Gautier, N., et al. (1992) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)50089-2 · Cited by 54 · see citing works
Hori, K., Yasuda, H., Konno, D., Maruoka, H., Tsumoto, T., & Sobue, K. (2005) · Journal of Neuroscience · doi:10.1523/jneurosci.3638-04.2005 · Cited by 44 · see citing works
Ruthazer, E. S., & Cline, H. T. (2002) · Real-Time Imaging · doi:10.1006/rtim.2002.0284 · Cited by 36 · see citing works
Self-citationcDNA Sequence Analysis of the Human Brain Insulin Receptor
Kenner, K. A., Kusari, J., & Heidenreich, K. A. (1995) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1995.2778 · Cited by 21 · see citing works
Kanezaki, Y., Obata, T., Matsushima, R., et al. (2004) · Endocrine Journal · doi:10.1507/endocrj.51.133 · Cited by 13 · see citing works
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Arnold, S. E., Arvanitakis, Z., Macauley-Rambach, S. L., Koenig, A. M., Wang, H.-Y., Ahima, R. S., Craft, S., Gandy, S., Buettner, C., Stoeckel, L. E., et al. (2018) · Nature Reviews Neurology · doi:10.1038/nrneurol.2017.185 · Cited by 1,597 · see citing works
Craft, S. (2012) · Archives of Neurology · doi:10.1001/archneurol.2011.233 · Cited by 1,253 · see citing works
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Lourenco, M. V., Frozza, R. L., de Freitas, G. B., Zhang, H., Kincheski, G. C., Ribeiro, F. C., Gonçalves, R. A., Clarke, J. R., Beckman, D., Staniszewski, A., et al. (2019) · Nature Medicine · doi:10.1038/s41591-018-0275-4 · Cited by 935 · see citing works
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Panza, F., Lozupone, M., Logroscino, G., & Imbimbo, B. P. (2019) · Nature Reviews Neurology · doi:10.1038/s41582-018-0116-6 · Cited by 965 · see citing works
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Fernandez, A. M., & Torres-Alemán, I. (2012) · Nature reviews. Neuroscience · doi:10.1038/nrn3209 · Cited by 872 · see citing works
Agrawal, M., Saraf, S., Saraf, S., Antimisiaris, S. G., Chougule, M. B., Shoyele, S. A., & Alexander, A. (2018) · Journal of Controlled Release · doi:10.1016/j.jconrel.2018.05.011 · Cited by 630 · see citing works
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Kleinridders, A., Cai, W., Cappellucci, L., Ghazarian, A., Collins, W. R., Vienberg, S. G., Pothos, E. N., & Kahn, C. R. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1500877112 · Cited by 486 · see citing works
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Gabbouj, S., Ryhänen, S., Marttinen, M., Wittrahm, R., Takalo, M., Kemppainen, S., Martiskainen, H., Tanila, H., Haapasalo, A., Hiltunen, M., et al. (2019) · Frontiers in Neuroscience · doi:10.3389/fnins.2019.00629 · Cited by 401 · see citing works
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- Authors
- Chiu, S.-L., Chen, C.-M., & Cline, H. T.
- Affiliations
- Cold Spring Harbor Laboratory (US)
- Corresponding author
- Cline, Hollis T.
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2008-06
- Volume
- 58
- Issue
- 5
- Pages
- 708-719
- ISSN
- 0896-6273 (ISSN-L)
- PMC
- PMC3057650
- OpenAlex
- W2163772343
- Cited by
- 425
- References
- 42
- Citations by year
- 2026: 15 · 2025: 11 · 2024: 22 · 2023: 20 · 2022: 23 · 2021: 32 · 2020: 37 · 2019: 29 · 2018: 42 · 2017: 16 · 2016: 26 · 2015: 31 · 2014: 27 · 2013: 26 · 2012: 24
- FWCI
- 6.21
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- Cold Spring Harbor Laboratory Institutional Repository (Cold Spring Harbor Laboratory) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (DP1OD000458)
- National Eye Institute (R01EY011261)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Keywords
- insulin receptor signaling, synaptic plasticity, synaptic density, dendritic plasticity, optic tectum, visual system, Xenopus tadpoles, light-evoked responses, synapse maturation, AMPA/NMDA ratio, morpholino knockdown, circuit function
- MeSH terms
- Animals, Chlorocebus aethiops, Dendrites, Models, Biological, Synaptic Transmission, Neuronal Plasticity, Neurons, Receptor, Insulin, Superior Colliculi, Synapses, Transfection, Xenopus laevis, Signal Transduction, alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid, Patch-Clamp Techniques, Excitatory Amino Acid Agonists, COS Cells, Microscopy, Electron, Transmission, Green Fluorescent Proteins
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