Abstract
Long-term memory and its putative synaptic correlates the late phases of both long-term potentiation and long-term depression require enhanced protein synthesis. On the basis of recent data on translation-dependent synaptic plasticity and on the supralinear effect of activation of nearby synapses on action potential generation, we propose a model for the formation of long-term memory engrams at the single neuron level. In this model, which we call clustered plasticity, local translational enhancement, along with synaptic tagging and capture, facilitates the formation of long-term memory engrams through bidirectional synaptic weight changes among synapses within a dendritic branch.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$189.00 per year
only $15.75 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Malenka, R. C. & Bear, M. F. LTP and LTD: an embarrassment of riches. Neuron 44, 5–21 (2004).
Davis, H. P. & Squire, L. R. Protein synthesis and memory: a review. Psychol. Bull. 96, 518–559 (1984).
Krug, M., Lossner, B. & Ott, T. Anisomycin blocks the late phase of long-term potentiation in the dentate gyrus of freely moving rats. Brain Res. Bull. 13, 39–42 (1984).
Frey, U., Krug, M., Reymann, K. G. & Matthies, H. Anisomycin, an inhibitor of protein synthesis, blocks late phases of LTP phenomena in the hippocampal CA1 region in vitro. Brain Res. 452, 57–65 (1988).
Frey, U. & Morris, R. G. Synaptic tagging and long-term potentiation. Nature 385, 533–536 (1997).
Huber, K. M., Kayser, M. S. & Bear, M. F. Role for rapid dendritic protein synthesis in hippocampal mGluR-dependent long-term depression. Science 288, 1254–1257 (2000).
Huber, K. M., Roder, J. C. & Bear, M. F. Chemical induction of mGluR5- and protein synthesis-dependent long-term depression in hippocampal area CA1. J. Neurophysiol. 86, 321–325 (2001).
Scharf, M. T. et al. Protein synthesis is required for the enhancement of long-term potentiation and long-term memory by spaced training. J. Neurophysiol. 87, 2770–2777 (2002).
Kelleher, R. J., Govindarajan, A. & Tonegawa, S. Translational regulatory mechanisms in persistent forms of synaptic plasticity. Neuron 44, 59–73 (2004).
Kelleher, R. J., Govindarajan, A., Jung, H. Y., Kang, H. & Tonegawa, S. Translational control by MAPK signaling in long-term synaptic plasticity and memory. Cell 116, 467–479 (2004).
Manahan-Vaughan, D., Kulla, A. & Frey, J. U. Requirement of translation but not transcription for the maintenance of long-term depression in the CA1 region of freely moving rats. J. Neurosci. 20, 8572–8576 (2000).
Otani, S., Marshall, C. J., Tate, W. P., Goddard, G. V. & Abraham, W. C. Maintenance of long-term potentiation in rat dentate gyrus requires protein synthesis but not messenger RNA synthesis immediately post-tetanization. Neuroscience 28, 519–526 (1989).
Nguyen, P. V., Abel, T. & Kandel, E. R. Requirement of a critical period of transcription for induction of a late phase of LTP. Science 265, 1104–1107 (1994).
Frey, U., Frey, S., Schollmeier, F. & Krug, M. Influence of actinomycin D, a RNA synthesis inhibitor, on long-term potentiation in rat hippocampal neurons in vivo and in vitro. J. Physiol. (London) 490, 703–711 (1996).
Kauderer, B. S. & Kandel, E. R. Capture of a protein synthesis-dependent component of long-term depression. Proc. Natl Acad. Sci. USA 97, 13342–13347 (2000).
Sajikumar, S. & Frey, J. U. Late-associativity, synaptic tagging, and the role of dopamine during LTP and LTD. Neurobiol. Learn. Mem. 82, 12–25 (2004).
Yuste, R. & Urban, R. Dendritic spines and linear networks. J. Physiol. (Paris) 98, 479–486 (2004).
Frey, J. U. Long-lasting hippocampal plasticity: cellular model for memory consolidation? Results Probl. Cell Differ. 34, 27–40 (2001).
Poirazi, P., Brannon, T. & Mel, B. W. Pyramidal neuron as two-layer neural network. Neuron 37, 989–999 (2003).
Poirazi, P., Brannon, T. & Mel, B. W. Arithmetic of subthreshold synaptic summation in a model CA1 pyramidal cell. Neuron 37, 977–987 (2003).
Poirazi, P. & Mel, B. W. Impact of active dendrites and structural plasticity on the memory capacity of neural tissue. Neuron 29, 779–796 (2001).
Klann, E. & Dever, T. E. Biochemical mechanisms for translational regulation in synaptic plasticity. Nature Rev. Neurosci. 5, 931–942 (2004).
Takei, N., Kawamura, M., Hara, K., Yonezawa, K. & Nawa, H. Brain-derived neurotrophic factor enhances neuronal translation by activating multiple initiation processes: comparison with the effects of insulin. J. Biol. Chem. 276, 42818–42825 (2001).
Takei, N. et al. Brain-derived neurotrophic factor induces mammalian target of rapamycin-dependent local activation of translation machinery and protein synthesis in neuronal dendrites. J. Neurosci. 24, 9760–9769 (2004).
Banko, J. L., Hou, L. & Klann, E. NMDA receptor activation results in PKA- and ERK-dependent Mnk1 activation and increased eIF4E phosphorylation in hippocampal area CA1. J. Neurochem. 91, 462–470 (2004).
Banko, J. L. et al. The translation repressor 4E-BP2 is critical for eIF4F complex formation, synaptic plasticity, and memory in the hippocampus. J. Neurosci. 25, 9581–9590 (2005).
Banko, J. L., Hou, L., Poulin, F., Sonenberg, N. & Klann, E. Regulation of eukaryotic initiation factor 4E by converging signaling pathways during metabotropic glutamate receptor-dependent long-term depression. J. Neurosci. 26, 2167–2173 (2006).
Tsokas, P. et al. Local protein synthesis mediates a rapid increase in dendritic elongation factor 1A after induction of late long-term potentiation. J. Neurosci. 25, 5833–5843 (2005).
Huang, F., Chotiner, J. K. & Steward, O. The mRNA for elongation factor 1α is localized in dendrites and translated in response to treatments that induce long-term depression. J. Neurosci. 25, 7199–7209 (2005).
English, J. D. & Sweatt, J. D. Activation of p42 mitogen-activated protein kinase in hippocampal long term potentiation. J. Biol. Chem. 271, 24329–24332 (1996).
English, J. D. & Sweatt, J. D. A requirement for the mitogen-activated protein kinase cascade in hippocampal long term potentiation. J. Biol. Chem. 272, 19103–19106 (1997).
Tang, S. J. et al. A rapamycin-sensitive signaling pathway contributes to long-term synaptic plasticity in the hippocampus. Proc. Natl Acad. Sci. USA 99, 467–472 (2002).
Hou, L. & Klann, E. Activation of the phosphoinositide 3-kinase-Akt-mammalian target of rapamycin signaling pathway is required for metabotropic glutamate receptor-dependent long-term depression. J. Neurosci. 24, 6352–6361 (2004).
Gallagher, S. M., Daly, C. A., Bear, M. F. & Huber, K. M. Extracellular signal-regulated protein kinase activation is required for metabotropic glutamate receptor-dependent long-term depression in hippocampal area CA1. J. Neurosci. 24, 4859–4864 (2004).
Gong, R., Park, C. S., Rezaei Abbassi, N. & Tang, S. J. Roles of glutamate receptors and the mTOR signaling pathway in activity-dependent dendritic protein synthesis in hippocampal neurons. J. Biol. Chem. 1 May 2006 [epub ahead of print].
Cammalleri, M. et al. Time-restricted role for dendritic activation of the mTOR-p70S6K pathway in the induction of late-phase long-term potentiation in the CA1. Proc. Natl Acad. Sci. USA 100, 14368–14373 (2003).
Steward, O. & Levy, W. B. Preferential localization of polyribosomes under the base of dendritic spines in granule cells of the dentate gyrus. J. Neurosci. 2, 284–291 (1982).
Steward, O. & Fass, B. Polyribosomes associated with dendritic spines in the denervated dentate gyrus: evidence for local regulation of protein synthesis during reinnervation. Prog. Brain Res. 58, 131–136 (1983).
Rao, A. & Steward, O. Evidence that protein constituents of postsynaptic membrane specializations are locally synthesized: analysis of proteins synthesized within synaptosomes. J. Neurosci. 11, 2881–2895 (1991).
Torre, E. R. & Steward, O. Demonstration of local protein synthesis within dendrites using a new cell culture system that permits the isolation of living axons and dendrites from their cell bodies. J. Neurosci. 12, 762–772 (1992).
Torre, E. R. & Steward, O. Protein synthesis within dendrites: glycosylation of newly synthesized proteins in dendrites of hippocampal neurons in culture. J. Neurosci. 16, 5967–5978 (1996).
Burgin, K. E. et al. In situ hybridization histochemistry of Ca2+/calmodulin-dependent protein kinase in developing rat brain. J. Neurosci. 10, 1788–1798 (1990).
Lowenstein, P. R. et al. Polarized distribution of the trans-Golgi network marker TGN38 during the in vitro development of neocortical neurons: effects of nocodazole and brefeldin A. Eur. J. Neurosci. 6, 1453–1465 (1994).
Tiedge, H. & Brosius, J. Translational machinery in dendrites of hippocampal neurons in culture. J. Neurosci. 16, 7171–7181 (1996).
Gardiol, A., Racca, C. & Triller, A. Dendritic and postsynaptic protein synthetic machinery. J. Neurosci. 19, 168–179 (1999).
Job, C. & Eberwine, J. Identification of sites for exponential translation in living dendrites. Proc. Natl Acad. Sci. USA 98, 13037–13042 (2001).
Steward, O. & Schuman, E. M. Protein synthesis at synaptic sites on dendrites. Annu. Rev. Neurosci. 24, 299–325 (2001).
Kang, H. & Schuman, E. M. A requirement for local protein synthesis in neurotrophin-induced hippocampal synaptic plasticity. Science 273, 1402–1406 (1996).
Kacharmina, J. E., Job, C., Crino, P. & Eberwine, J. Stimulation of glutamate receptor protein synthesis and membrane insertion within isolated neuronal dendrites. Proc. Natl Acad. Sci. USA 97, 11545–11550 (2000).
Aakalu, G., Smith, W. B., Nguyen, N., Jiang, C. & Schuman, E. M. Dynamic visualization of local protein synthesis in hippocampal neurons. Neuron 30, 489–502 (2001).
Martin, K. C. & Kosik, K. S. Synaptic tagging — who's it? Nature Rev. Neurosci. 3, 813–820 (2002).
Ju, W. et al. Activity-dependent regulation of dendritic synthesis and trafficking of AMPA receptors. Nature Neurosci. 7, 244–253 (2004).
Bradshaw, K. D., Emptage, N. J. & Bliss, T. V. A role for dendritic protein synthesis in hippocampal late LTP. Eur. J. Neurosci. 18, 3150–3152 (2003).
Vickers, C. A., Dickson, K. S. & Wyllie, D. J. Induction and maintenance of late-phase long-term potentiation in isolated dendrites of rat hippocampal CA1 pyramidal neurones. J. Physiol. (London) 568, 803–813 (2005).
Smith, W. B., Starck, S. R., Roberts, R. W. & Schuman, E. M. Dopaminergic stimulation of local protein synthesis enhances surface expression of GluR1 and synaptic transmission in hippocampal neurons. Neuron 45, 765–779 (2005).
Augustine, G. J., Santamaria, F. & Tanaka, K. Local calcium signaling in neurons. Neuron 40, 331–346 (2003).
Sawano, A., Takayama, S., Matsuda, M. & Miyawaki, A. Lateral propagation of EGF signaling after local stimulation is dependent on receptor density. Dev. Cell 3, 245–257 (2002).
Dudek, S. M. & Fields, R. D. Mitogen-activated protein kinase/extracellular signal-regulated kinase activation in somatodendritic compartments: roles of action potentials, frequency, and mode of calcium entry. J. Neurosci. 21, RC122 (2001).
Dudek, S. M. & Fields, R. D. Somatic action potentials are sufficient for late-phase LTP-related cell signaling. Proc. Natl Acad. Sci. USA 99, 3962–3967 (2002).
Selcher, J. C. et al. A role for ERK MAP kinase in physiologic temporal integration in hippocampal area CA1. Learn. Mem. 10, 26–39 (2003).
Wu, G. Y., Deisseroth, K. & Tsien, R. W. Spaced stimuli stabilize MAPK pathway activation and its effects on dendritic morphology. Nature Neurosci. 4, 151–158 (2001).
Wu, G. Y., Deisseroth, K. & Tsien, R. W. Activity-dependent CREB phosphorylation: convergence of a fast, sensitive calmodulin kinase pathway and a slow, less sensitive mitogen-activated protein kinase pathway. Proc. Natl Acad. Sci. USA 98, 2808–2813 (2001).
Rhodes, P. A. in Cerebral Cortex (eds Ulinski, P., Jones, E. G. & Peters, A.) 139–200 (Plenum, New York, 1999).
Golding, N. L., Staff, N. P. & Spruston, N. Dendritic spikes as a mechanism for cooperative long-term potentiation. Nature 418, 326–331 (2002).
Gasparini, S., Migliore, M. & Magee, J. C. On the initiation and propagation of dendritic spikes in CA1 pyramidal neurons. J. Neurosci. 24, 11046–11056 (2004).
Sweatt, J. D. Mitogen-activated protein kinases in synaptic plasticity and memory. Curr. Opin. Neurobiol. 14, 311–317 (2004).
Gelinas, J. N. & Nguyen, P. V. β-Adrenergic receptor activation facilitates induction of a protein synthesis-dependent late phase of long-term potentiation. J. Neurosci. 25, 3294–3303 (2005).
Huang, Y. Y. & Kandel, E. R. D1/D5 receptor agonists induce a protein synthesis-dependent late potentiation in the CA1 region of the hippocampus. Proc. Natl Acad. Sci. USA 92, 2446–2450 (1995).
Mockett, B. G., Brooks, W. M., Tate, W. P. & Abraham, W. C. Dopamine D1/D5 receptor activation fails to initiate an activity-independent late-phase LTP in rat hippocampus. Brain Res. 1021, 92–100 (2004).
Frey, U., Matthies, H., Reymann, K. G. & Matthies, H. The effect of dopaminergic D1 receptor blockade during tetanization on the expression of long-term potentiation in the rat CA1 region in vitro. Neurosci. Lett. 129, 111–114 (1991).
Frey, U., Schroeder, H. & Matthies, H. Dopaminergic antagonists prevent long-term maintenance of posttetanic LTP in the CA1 region of rat hippocampal slices. Brain Res. 522, 69–75 (1990).
Schultz, W. & Dickinson, A. Neuronal coding of prediction errors. Annu. Rev. Neurosci. 23, 473–500 (2000).
Otmakhova, N. A. & Lisman, J. E. D1/D5 dopamine receptor activation increases the magnitude of early long-term potentiation at CA1 hippocampal synapses. J. Neurosci. 16, 7478–7486 (1996).
Swanson-Park, J. L. et al. A double dissociation within the hippocampus of dopamine D1/D5 receptor and β-adrenergic receptor contributions to the persistence of long-term potentiation. Neuroscience 92, 485–497 (1999).
Lee, K. S. Cooperativity among afferents for the induction of long-term potentiation in the CA1 region of the hippocampus. J. Neurosci. 3, 1369–1372 (1983).
Bennett, M. R. The concept of long term potentiation of transmission at synapses. Prog. Neurobiol. 60, 109–137 (2000).
Bear, M. F. A synaptic basis for memory storage in the cerebral cortex. Proc. Natl Acad. Sci. USA 93, 13453–13459 (1996).
Frey, U. & Morris, R. G. Weak before strong: dissociating synaptic tagging and plasticity-factor accounts of late-LTP. Neuropharmacology 37, 545–552 (1998).
O'Carroll, C. M. & Morris, R. G. Heterosynaptic co-activation of glutamatergic and dopaminergic afferents is required to induce persistent long-term potentiation. Neuropharmacology 47, 324–332 (2004).
Fonseca, R., Nagerl, U. V., Morris, R. G. & Bonhoeffer, T. Competing for memory; hippocampal LTP under regimes of reduced protein synthesis. Neuron 44, 1011–1020 (2004).
Frey, U. & Morris, R. G. Synaptic tagging: implications for late maintenance of hippocampal long-term potentiation. Trends Neurosci. 21, 181–188 (1998).
Washbourne, P., Bennett, J. E. & McAllister, A. K. Rapid recruitment of NMDA receptor transport packets to nascent synapses. Nature Neurosci. 5, 751–759 (2002).
Bannister, N. J. & Larkman, A. U. Dendritic morphology of CA1 pyramidal neurones from the rat hippocampus: I. Branching patterns. J. Comp. Neurol. 360, 150–160 (1995).
Trommald, M., Jensen, V. & Andersen, P. Analysis of dendritic spines in rat CA1 pyramidal cells intracellularly filled with a fluorescent dye. J. Comp. Neurol. 353, 260–274 (1995).
Alarcon, J. M., Barco, A. & Kandel, E. R. Capture of the late phase of long-term potentiation within and across the apical and basilar dendritic compartments of CA1 pyramidal neurons: synaptic tagging is compartment restricted. J. Neurosci. 26, 256–264 (2006).
Martin, S. J. & Morris, R. G. New life in an old idea: the synaptic plasticity and memory hypothesis revisited. Hippocampus 12, 609–636 (2002).
Gasparini, S. & Magee, J. C. State-dependent dendritic computation in hippocampal CA1 pyramidal neurons. J. Neurosci. 26, 2088–2100 (2006).
Polsky, A., Mel, B. W. & Schiller, J. Computational subunits in thin dendrites of pyramidal cells. Nature Neurosci. 7, 621–627 (2004).
Losonczy, A. & Magee, J. C. Integrative properties of radial oblique dendrites in hippocampal CA1 pyramidal neurons. Neuron 50, 291–307 (2006).
Mehta, M. R. Cooperative LTP can map memory sequences on dendritic branches. Trends Neurosci. 27, 69–72 (2004).
Wilson, M. A. & McNaughton, B. L. Dynamics of the hippocampal ensemble code for space. Science 261, 1055–1058 (1993).
Nakazawa, K., McHugh, T. J., Wilson, M. A. & Tonegawa, S. NMDA receptors, place cells and hippocampal spatial memory. Nature Rev. Neurosci. 5, 361–372 (2004).
Otto, T., Eichenbaum, H., Wiener, S. I. & Wible, C. G. Learning-related patterns of CA1 spike trains parallel stimulation parameters optimal for inducing hippocampal long-term potentiation. Hippocampus 1, 181–192 (1991).
Stewart, M., Luo, Y. & Fox, S. E. Effects of atropine on hippocampal theta cells and complex-spike cells. Brain Res. 591, 122–128 (1992).
Jeffery, K. J., Donnett, J. G. & O'Keefe, J. Medial septal control of theta-correlated unit firing in the entorhinal cortex of awake rats. Neuroreport 6, 2166–2170 (1995).
Holscher, C. Synaptic plasticity and learning and memory: LTP and beyond. J. Neurosci. Res. 58, 62–75 (1999).
Petersen, C. C., Malenka, R. C., Nicoll, R. A. & Hopfield, J. J. All-or-none potentiation at CA3–CA1 synapses. Proc. Natl Acad. Sci. USA 95, 4732–4737 (1998).
O'Neill, J., Senior, T. & Csicsvari, J. Place-selective firing of CA1 pyramidal cells during sharp wave/ripple network patterns in exploratory behavior. Neuron 49, 143–155 (2006).
Foster, D. J. & Wilson, M. A. Reverse replay of behavioural sequences in hippocampal place cells during the awake state. Nature 440, 680–683 (2006).
Guzowski, J. F., McNaughton, B. L., Barnes, C. A. & Worley, P. F. Environment-specific expression of the immediate-early gene Arc in hippocampal neuronal ensembles. Nature Neurosci. 2, 1120–1124 (1999).
Tsien, R. Y. Imagining imaging's future. Nature Rev. Mol. Cell Biol. 4 (Suppl.), SS16–SS21 (2003).
Brecht, M. et al. Novel approaches to monitor and manipulate single neurons in vivo. J. Neurosci. 24, 9223–9227 (2004).
Mehta, A. D., Jung, J. C., Flusberg, B. A. & Schnitzer, M. J. Fiber optic in vivo imaging in the mammalian nervous system. Curr. Opin. Neurobiol. 14, 617–628 (2004).
Miyawaki, A. Innovations in the imaging of brain functions using fluorescent proteins. Neuron 48, 189–199 (2005).
Barco, A., Alarcon, J. M. & Kandel, E. R. Expression of constitutively active CREB protein facilitates the late phase of long-term potentiation by enhancing synaptic capture. Cell 108, 689–703 (2002).
Woo, N. H. & Nguyen, P. V. 'Silent' metaplasticity of the late phase of long-term potentiation requires protein phosphatases. Learn. Mem. 9, 202–213 (2002).
Woo, N. H. & Nguyen, P. V. Protein synthesis is required for synaptic immunity to depotentiation. J. Neurosci. 23, 1125–1132 (2003).
Fiala, J. C. & Harris, K. M. in Dendrites (eds Stuart, G., Spruston, N. & Häusser, M.) 376 (Oxford Univ. Press, New York, 1999).
Acknowledgements
We thank C. Stevens, M. Wilson and members of the Tonegawa laboratory for helpful discussions, and critical reading of and comments on the manuscript. Research was supported by the RIKEN-MIT Neuroscience Research Center, Howard Hughes Medical Institute and grants from the National Institutes of Health (S.T. and R.J.K).
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Competing interests
The authors declare no competing financial interests.
Glossary
- Antidromic
-
Conduction of an action potential in the opposite direction to normal — that is, towards the cell soma.
- Associativity
-
When stimulation at one synapse is too weak to induce LTP, the simultaneous strong stimulation of another synapse can be sufficient to trigger LTP at both.
- Cooperativity
-
When multiple synaptic inputs that are individually insufficient to induce LTP (or LTD) can collectively produce a postsynaptic depolarization that is sufficient to trigger LTP (or LTD).
- Dedepression
-
A reversal of LTD by high-frequency synaptic stimulation. Dedepression shares some characteristics with LTP — both are induced by high-frequency stimulation, and both require NMDAR and protein kinase activity. However, there is evidence that LTP and dedepression are different processes.
- Depotentiation
-
A reversal of LTP by low-frequency synaptic stimulation. Depotentiation shares some characteristics with LTD — both are induced by low-frequency stimulation, and both require NMDAR and protein phosphatase activity. However, there is evidence that LTD and depotentiation are different processes.
- Engram
-
A persistent change in the brain that is formed in response to a stimulus, and is the neuronal substrate for a memory (also known as a memory trace).
- Immediate-early gene
-
Genes that are induced within minutes of intense neuronal activity, even in the absence of protein synthesis. They are often induced by behavioural training. Examples include Zif268, c-fos and Arc.
- Mammalian target of rapamycin
-
(mTOR). An evolutionarily conserved kinase, originally found to be stimulated by nutrients, that is a component of one of two key pathways in general translational regulation.
- Mitogen-activated protein kinase
-
(MAPK). Any member of a family of evolutionarily conserved kinases (consisting of multiple isoforms of extracellular signal-regulated kinases, c-Jun N-terminal kinases, p38 MAPKs), originally found to be stimulated by growth factors, that are important in relaying signals from the cell membrane to various parts of a cell, including the nucleus, translational machinery, ion channels and cytoskeleton. The MAPK pathway is one of two key pathways in regulating general translation.
- Sharp waves
-
Large amplitude electroencephalogram potentials that are the result of coherent neuronal discharges observed in the hippocampus and are accompanied by high-frequency (∼200 Hz) oscillations during certain behavioural states.
- Synaptic tag
-
Stimulated synapses are tagged in a protein synthesis-independent manner to distinguish them from other synapses on the same neuron that have not been activated. This mechanism enables tagged synapses to capture proteins required for, and to express, late-phase forms of plasticity, even when they receive stimuli that would normally result in early-phase forms of plasticity.
- Synaptic weight
-
The relative amplitude of the postsynaptic response that is generated by the activity of the presynaptic neuron (also known as synaptic strength).
- Theta-burst stimulation
-
Rhythmic neural activity with a frequency of 4–8 Hz that is present in several parts of the brain during certain behavioural states.
Rights and permissions
About this article
Cite this article
Govindarajan, A., Kelleher, R. & Tonegawa, S. A clustered plasticity model of long-term memory engrams. Nat Rev Neurosci 7, 575–583 (2006). https://doi.org/10.1038/nrn1937
Issue Date:
DOI: https://doi.org/10.1038/nrn1937
This article is cited by
-
Generalized extinction of fear memory depends on co-allocation of synaptic plasticity in dendrites
Nature Communications (2023)
-
Learning binds new inputs into functional synaptic clusters via spinogenesis
Nature Neuroscience (2022)
-
Astrocytic microdomains from mouse cortex gain molecular control over long-term information storage and memory retention
Communications Biology (2021)
-
Dendritic spines are lost in clusters in Alzheimer’s disease
Scientific Reports (2021)