Learning binds new inputs into functional synaptic clusters via spinogenesis.
Journal
Nature neuroscience
ISSN: 1546-1726
Titre abrégé: Nat Neurosci
Pays: United States
ID NLM: 9809671
Informations de publication
Date de publication:
06 2022
06 2022
Historique:
received:
26
01
2021
accepted:
26
04
2022
pubmed:
3
6
2022
medline:
10
6
2022
entrez:
2
6
2022
Statut:
ppublish
Résumé
Learning induces the formation of new excitatory synapses in the form of dendritic spines, but their functional properties remain unknown. Here, using longitudinal in vivo two-photon imaging and correlated electron microscopy of dendritic spines in the motor cortex of mice during motor learning, we describe a framework for the formation, survival and resulting function of new, learning-related spines. Specifically, our data indicate that the formation of new spines during learning is guided by the potentiation of functionally clustered preexisting spines exhibiting task-related activity during earlier sessions of learning. We present evidence that this clustered potentiation induces the local outgrowth of multiple filopodia from the nearby dendrite, locally sampling the adjacent neuropil for potential axonal partners, likely via targeting preexisting presynaptic boutons. Successful connections are then selected for survival based on co-activity with nearby task-related spines, ensuring that the new spine preserves functional clustering. The resulting locally coherent activity of new spines signals the learned movement. Furthermore, we found that a majority of new spines synapse with axons previously unrepresented in these dendritic domains. Thus, learning involves the binding of new information streams into functional synaptic clusters to subserve learned behaviors.
Identifiants
pubmed: 35654957
doi: 10.1038/s41593-022-01086-6
pii: 10.1038/s41593-022-01086-6
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
726-737Subventions
Organisme : NEI NIH HHS
ID : R01 EY025349
Pays : United States
Organisme : NIDCD NIH HHS
ID : R01 DC014690
Pays : United States
Organisme : NEI NIH HHS
ID : P30 EY022589
Pays : United States
Organisme : NINDS NIH HHS
ID : F32 NS103267
Pays : United States
Organisme : NINDS NIH HHS
ID : U24 NS120055
Pays : United States
Organisme : NIDA NIH HHS
ID : R01 DA049787
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM082949
Pays : United States
Organisme : NINDS NIH HHS
ID : K99 NS114175
Pays : United States
Organisme : NINDS NIH HHS
ID : R21 NS112750
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS091010
Pays : United States
Organisme : NIMH NIH HHS
ID : U01 MH114829
Pays : United States
Organisme : NIGMS NIH HHS
ID : R24 GM137200
Pays : United States
Organisme : NINDS NIH HHS
ID : R21 NS109722
Pays : United States
Organisme : NIDA NIH HHS
ID : R01 DA038896
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS121231
Pays : United States
Informations de copyright
© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.
Références
Makino, H., Hwang, E. J., Hedrick, N. G. & Komiyama, T. Circuit mechanisms of sensorimotor learning. Neuron https://doi.org/10.1016/j.neuron.2016.10.029 (2016).
Hofer, S. B., Mrsic-Flogel, T. D., Bonhoeffer, T. & Hübener, M. Experience leaves a lasting structural trace in cortical circuits. Nature 457, 313–317 (2009).
doi: 10.1038/nature07487
pubmed: 19005470
Xu, T. et al. Rapid formation and selective stabilization of synapses for enduring motor memories. Nature 462, 915–919 (2009).
doi: 10.1038/nature08389
pubmed: 19946267
pmcid: 2844762
Fu, M., Yu, X., Lu, J. & Zuo, Y. Repetitive motor learning induces coordinated formation of clustered dendritic spines in vivo. Nature 483, 92–95 (2012).
doi: 10.1038/nature10844
pubmed: 22343892
pmcid: 3292711
Iacaruso, M. F., Gasler, I. T. & Hofer, S. B. Synaptic organization of visual space in primary visual cortex. Nature https://doi.org/10.1038/nature23019 (2017).
Wilson, D. E., Whitney, D. E., Scholl, B. & Fitzpatrick, D. Orientation selectivity and the functional clustering of synaptic inputs in primary visual cortex. Nat. Neurosci. 19, 1003–1009 (2016).
doi: 10.1038/nn.4323
pubmed: 27294510
pmcid: 5240628
Scholl, B., Wilson, D. E. & Fitzpatrick, D. Local order within global disorder: synaptic architecture of visual space. Neuron https://doi.org/10.1016/j.neuron.2017.10.017 (2017).
Kerlin, A. et al. Functional clustering of dendritic activity during decision-making. Elife https://doi.org/10.7554/eLife.46966 (2019).
Peters, A. J., Chen, S. X. & Komiyama, T. Emergence of reproducible spatiotemporal activity during motor learning. Nature 510, 263–267 (2014).
doi: 10.1038/nature13235
pubmed: 24805237
Chen, S. X., Kim, A. N., Peters, A. J. & Komiyama, T. Subtype-specific plasticity of inhibitory circuits in motor cortex during motor learning. Nat. Neurosci. 18, 1109–1115 (2015).
doi: 10.1038/nn.4049
pubmed: 26098758
pmcid: 4519436
Marvin, J. S. et al. An optimized fluorescent probe for visualizing glutamate neurotransmission. Nat. Methods https://doi.org/10.1038/nmeth.2333 (2013).
Marvin, J. S. et al. Stability, affinity, and chromatic variants of the glutamate sensor iGluSnFR. Nat. Methods https://doi.org/10.1038/s41592-018-0171-3 (2018).
Hires, S. A., Zhu, Y. & Tsien, R. Y. Optical measurement of synaptic glutamate spillover and reuptake by linker optimized glutamate-sensitive fluorescent reporters. Proc. Natl. Acad. Sci. USA https://doi.org/10.1073/pnas.0712008105 (2008).
Chen, T.-W. et al. Ultrasensitive fluorescent proteins for imaging neuronal activity. Nature 499, 295–300 (2013).
doi: 10.1038/nature12354
pubmed: 23868258
pmcid: 3777791
Kerlin, A. et al. Functional clustering of dendritic activity during decision-making. eLife https://doi.org/10.7554/eLife.46966 (2018).
Peters, A. J., Lee, J., Hedrick, N. G., O’Neil, K. & Komiyama, T. Reorganization of corticospinal output during motor learning. Nat. Neurosci. 20, 1133–1141 (2017).
doi: 10.1038/nn.4596
pubmed: 28671694
pmcid: 5656286
Takahashi, N. et al. Locally synchronized synaptic inputs. Science 335, 353–356 (2012).
doi: 10.1126/science.1210362
pubmed: 22267814
De Roo, M., Klauser, P. & Muller, D. LTP promotes a selective long-term stabilization and clustering of dendritic spines. PLoS Biol. https://doi.org/10.1371/journal.pbio.0060219 (2008).
Kastellakis, G., Cai, D. J., Mednick, S. C., Silva, A. J. & Poirazi, P. Synaptic clustering within dendrites: an emerging theory of memory formation. Prog. Neurobiol. 126, 19–35 (2015).
Kleindienst, T., Winnubst, J., Roth-Alpermann, C., Bonhoeffer, T. & Lohmann, C. Activity-dependent clustering of functional synaptic inputs on developing hippocampal dendrites. Neuron https://doi.org/10.1016/j.neuron.2011.10.015 (2011).
Makino, H. & Malinow, R. AMPA receptor incorporation into synapses during LTP: the role of lateral movement and exocytosis. Neuron 64, 381–390 (2009).
doi: 10.1016/j.neuron.2009.08.035
pubmed: 19914186
pmcid: 2999463
Makino, H. & Malinow, R. Compartmentalized versus global synaptic plasticity on dendrites controlled by experience. Neuron https://doi.org/10.1016/j.neuron.2011.09.036 (2011).
Hedrick, N. et al. Rho GTPase complementation underlies BDNF-dependent homo- and heterosynaptic plasticity. Nature 538, 104–108 (2016).
doi: 10.1038/nature19784
pubmed: 27680697
pmcid: 5361895
Kwon, H.-B. & Sabatini, B. L. Glutamate induces de novo growth of functional spines in developing cortex. Nature 474, 100–104 (2011).
doi: 10.1038/nature09986
pubmed: 21552280
pmcid: 3107907
Matsuzaki, M., Honkura, N., Ellis-Davies, G. C. R. & Kasai, H. Structural basis of long-term potentiation in single dendritic spines. Nature 429, 761–766 (2004).
doi: 10.1038/nature02617
pubmed: 15190253
pmcid: 4158816
Cichon, J. & Gan, W.-B. Branch-specific dendritic Ca
doi: 10.1038/nature14251
pubmed: 25822789
pmcid: 4476301
Murakoshi, H., Wang, H. & Yasuda, R. Local, persistent activation of Rho GTPases during plasticity of single dendritic spines. Nature 472, 100–104 (2011).
doi: 10.1038/nature09823
pubmed: 21423166
pmcid: 3105377
Spacek, J. & Harris, K. M. Three-dimensional organization of smooth endoplasmic reticulum in hippocampal CA1 dendrites and dendritic spines of the immature and mature rat. J. Neurosci. https://doi.org/10.1523/jneurosci.17-01-00190.1997 (1997).
Deller, T. et al. Synaptopodin-deficient mice lack a spine apparatus and show deficits in synaptic plasticity. Proc. Natl. Acad. Sci. USA https://doi.org/10.1073/pnas.1832384100 (2003).
Hwang, E. J. et al. Disengagement of motor cortex from movement control during long-term learning. Sci. Adv. https://doi.org/10.1126/sciadv.aay0001 (2019).
Conner, J. M., Culberson, A., Packowski, C., Chiba, A. A. & Tuszynski, M. H. Lesions of the basal forebrain cholinergic system impair task acquisition and abolish cortical plasticity associated with motor skill learning. Neuron 38, 819–829 (2003).
doi: 10.1016/S0896-6273(03)00288-5
pubmed: 12797965
Kawai, R. et al. Motor cortex is required for learning but not for executing a motor skill. Neuron 86, 800–812 (2015).
doi: 10.1016/j.neuron.2015.03.024
pubmed: 25892304
pmcid: 5939934
Losonczy, A. & Magee, J. C. Integrative properties of radial oblique dendrites in hippocampal CA1 pyramidal neurons. Neuron 50, 291–307 (2006).
doi: 10.1016/j.neuron.2006.03.016
pubmed: 16630839
Niell, C. M., Meyer, M. P. & Smith, S. J. In vivo imaging of synapse formation on a growing dendritic arbor. Nat. Neurosci. https://doi.org/10.1038/nn1191 (2004).
Ziv, N. E. & Smith, S. J. Evidence for a role of dendritic filopodia in synaptogenesis and spine formation. Neuron https://doi.org/10.1016/S0896-6273(00)80283-4 (1996).
Toni, N. et al. Synapse formation on neurons born in the adult hippocampus. Nat. Neurosci. https://doi.org/10.1038/nn1908 (2007).
Dailey, M. E. & Smith, S. J. The dynamics of dendritic structure in developing hippocampal slices. J. Neurosci. https://doi.org/10.1523/jneurosci.16-09-02983.1996 (1996).
Lendvai, B., Stern, E. A., Chen, B. & Svoboda, K. Experience-dependent plasticity of dendritic spines in the developing rat barrel cortex in vivo. Nature 404, 876–881 (2000).
doi: 10.1038/35009107
pubmed: 10786794
Zuo, Y., Lin, A., Chang, P. & Gan, W. -B. Development of long-term dendritic spine stability in diverse regions of cerebral cortex. Neuron 46, 181–189 (2005).
Cruz-Martín, A., Crespo, M. & Portera-Cailliau, C. Delayed stabilization of dendritic spines in fragile X mice. J. Neurosci. 30, 7793–7803 (2010).
doi: 10.1523/JNEUROSCI.0577-10.2010
pubmed: 20534828
pmcid: 2903441
Holtmaat, A. J. G. D. et al. Transient and persistent dendritic spines in the neocortex in vivo. Neuron 45, 279–291 (2005).
doi: 10.1016/j.neuron.2005.01.003
pubmed: 15664179
Frank, A. C. et al. Hotspots of dendritic spine turnover facilitate clustered spine addition and learning and memory. Nat. Commun. https://doi.org/10.1038/s41467-017-02751-2 (2018).
Knott, G. W., Holtmaat, A., Wilbrecht, L., Welker, E. & Svoboda, K. Spine growth precedes synapse formation in the adult neocortex in vivo. Nat. Neurosci. 9, 1117–1124 (2006).
doi: 10.1038/nn1747
pubmed: 16892056
Yang, Y. et al. Selective synaptic remodeling of amygdalocortical connections associated with fear memory. Nat. Neurosci. https://doi.org/10.1038/nn.4370 (2016).
Lee, K. J. et al. Motor skill training induces coordinated strengthening and weakening between neighboring synapses. J. Neurosci. https://doi.org/10.1523/JNEUROSCI.0848-12.2013 (2013).
Toni, N., Buchs, P. A., Nikonenko, I., Bron, C. R. & Muller, D. LTP promotes formation of multiple spine synapses between a single axon terminal and a dendrite. Nature https://doi.org/10.1038/46574 (1999).
Niculescu, D. et al. A BDNF-mediated push–pull plasticity mechanism for synaptic clustering. Cell Rep. https://doi.org/10.1016/j.celrep.2018.07.073 (2018).
Bloss, E. B. et al. Single excitatory axons form clustered synapses onto CA1 pyramidal cell dendrites. Nat. Neurosci. https://doi.org/10.1038/s41593-018-0084-6 (2018).
Chicurel, M. E. & Harris, K. M. Three‐dimensional analysis of the structure and composition of CA3 branched dendritic spines and their synaptic relationships with mossy fiber boutons in the rat hippocampus. J. Comp. Neurol. https://doi.org/10.1002/cne.903250204 (1992).
Kasthuri, N. et al. Saturated reconstruction of a volume of nocortex. Cell https://doi.org/10.1016/j.cell.2015.06.054 (2015).
Govindarajan, A., Kelleher, R. J. & Tonegawa, S. A clustered plasticity model of long-term memory engrams. Nat. Rev. Neurosci. 7, 575–583 (2006).
doi: 10.1038/nrn1937
pubmed: 16791146
Poirazi, P. & Mel, B. W. Impact of active dendrites and structural plasticity on the memory capacity of neural tissue. Neuron 29, 779–796 (2001).
doi: 10.1016/S0896-6273(01)00252-5
pubmed: 11301036
Tjia, M., Yu, X., Jammu, L. S., Lu, J. & Zuo, Y. Pyramidal neurons in different cortical layers exhibit distinct dynamics and plasticity of apical dendritic spines. Front. Neural Circuits 11, 43 (2017).
doi: 10.3389/fncir.2017.00043
pubmed: 28674487
pmcid: 5474458
Mitani, A. & Komiyama, T. Real-time processing of two-photon calcium imaging data including lateral motion artifact correction. Front. Neuroinform. https://doi.org/10.3389/fninf.2018.00098 (2018).
Kremer, J. R., Mastronarde, D. N. & McIntosh, J. R. R. Computer visualization of three-dimensional image data using IMOD. J. Struct. Biol. 116, 71–76 (1996).
doi: 10.1006/jsbi.1996.0013
pubmed: 8742726