Abstract
To examine how functional circuits are established in the brain, we studied excitatory transmission in early postnatal hippocampus. Spontaneous neural activity was sufficient to selectively deliver GluR4-containing AMPA receptors (AMPA-Rs) into synapses. This delivery allowed non-functional connections to transmit at resting potentials and required NMDA receptors (NMDA-Rs) but not CaMKII activation. Subsequently, these delivered receptors were exchanged with non-synaptic GluR2-containing AMPA-Rs in a manner requiring little neuronal activity. The enhanced transmission resulting from this delivery and subsequent exchange was maintained for at least several days and required an interaction between GluR2 and NSF. Thus, this sequence of subunit-specific trafficking events triggered by spontaneous activity in early postnatal development may be crucial for initial establishment of long-lasting functional circuitry.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$209.00 per year
only $17.42 per issue
Rent or buy this article
Prices vary by article type
from$1.95
to$39.95
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Ramon y Cajal, S. Histologie du System Nerveux de l'Homme et Vertebres (Instituto Ramon y Cajal, Madrid, 1911).
Goodman, C. S. & Shatz, C. J. Developmental mechanisms that generate precise patterns of neuronal connectivity. Cell 72 Suppl., 77–98 (1993).
O'Brien, R. J. et al. Synaptic clustering of AMPA receptors by the extracellular immediate-early gene product Narp. Neuron 23, 309–323 (1999).
Scheiffele, P., Fan, J., Choih, J., Fetter, R. & Serafini, T. Neuroligin expressed in nonneuronal cells triggers presynaptic development in contacting axons. Cell 101, 657–669 (2000).
Cline, H. T., Wu, G. Y. & Malinow, R. In vivo development of neuronal structure and function . Cold Spring Harb. Symp. Quant. Biol. 61, 95–104 (1996).
Dingledine, R., Borges, K., Bowie, D. & Traynelis, S. F. The glutamate receptor ion channels. Pharmacol. Rev. 51, 7–61 (1999).
Petralia, R. S. et al. Selective acquisition of AMPA receptors over postnatal development suggests a molecular basis for silent synapses. Nat. Neurosci. 2, 31–36 (1999 ).
Liao, D., Zhang, X., O'Brien, R., Ehlers, M. D. & Huganir, R. L. Regulation of morphological postsynaptic silent synapses in developing hippocampal neurons. Nat. Neurosci. 2 , 37–43 (1999).
Wu, G., Malinow, R. & Cline, H. T. Maturation of a central glutamatergic synapse. Science 274, 972–976 ( 1996).
Durand, G. M., Kovalchuk, Y. & Konnerth, A. Long-term potentiation and functional synapse induction in developing hippocampus. Nature 381, 71 –75 (1996).
Isaac, J. T., Crair, M. C., Nicoll, R. A. & Malenka, R. C. Silent synapses during development of thalamocortical inputs. Neuron 18, 269–280 ( 1997).
Shi, S. H. et al. Rapid spine delivery and redistribution of AMPA receptors after synaptic NMDA receptor activation. Science 284 , 1811–1816 (1999).
Hayashi, Y. et al. Driving AMPA receptors into synapses by LTP and CaMKII: requirement for GluR1 and PDZ domain interaction. Science 287, 2262–2267 (2000).
Constantine-Paton, M. & Cline, H. T. LTP and activity-dependent synaptogenesis: the more alike they are, the more different they become. Curr. Opin. Neurobiol. 8, 139–148 (1998).
Nishimune, A. et al. NSF binding to GluR2 regulates synaptic transmission. Neuron 21, 87–97 ( 1998).
Osten, P. et al. The AMPA receptor GluR2 C terminus can mediate a reversible, ATP- dependent interaction with NSF and alpha- and beta-SNAPs. Neuron 21, 99–110 ( 1998).
Song, I. et al. Interaction of the N-ethylmaleimide-sensitive factor with AMPA receptors. Neuron 21, 393– 400 (1998).
Luthi, A. et al. Hippocampal LTD expression involves a pool of AMPARs regulated by the NSF-GluR2 interaction. Neuron 24, 389–399 (1999).
Luscher, C. et al. Role of AMPA receptor cycling in synaptic transmission and plasticity. Neuron 24, 649– 658 (1999).
Malinow, R. et al. in Imaging Neurons: A Laboratory Manual (eds. Yuste, R., Lanni, F. & Konnerth, A) 58.1–58.8 (Cold Spring Harbor Laboratory Press, Cold Spring Harbor, New York, 1999).
Verdoorn, T. A., Burnashev, N., Monyer, H., Seeburg, P. H. & Sakmann, B. Structural determinants of ion flow through recombinant glutamate receptor channels. Science 252, 1715–1718 (1991).
Hestrin, S., Nicoll, R. A., Perkel, D. J. & Sah, P. Analysis of excitatory synaptic action in pyramidal cells using whole-cell recording from rat hippocampal slices. J. Physiol. (Lond.) 422, 203–225 (1990).
Ben-Ari, Y., Cherubini, E., Corradetti, R. & Gaiarsa, J. L. Giant synaptic potentials in immature rat CA3 hippocampal neurones. J. Physiol. (Lond.) 416, 303–325 (1989).
Garaschuk, O., Hanse, E. & Konnerth, A. Developmental profile and synaptic origin of early network oscillations in the CA1 region of rat neonatal hippocampus. J. Physiol. (Lond.) 507, 219–236 (1998).
Palva, J. M. et al. Fast network oscillations in the newborn rat hippocampus in vitro. J. Neurosci. 20, 1170– 1178 (2000).
Margrie, T. W., Rostas, J. A. & Sah, P. Presynaptic long-term depression at a central glutamatergic synapse: a role for CaMKII. Nat. Neurosci. 1, 378–383 (1998).
Lisman, J., Malenka, R. C., Nicoll, R. A. & Malinow, R. Learning mechanisms: the case for CaM-KII. Science 276, 2001–2002 (1997).
Liao, D. & Malinow, R. Deficiency in induction but not expression of LTP in hippocampal slices from young rats. Learn. Mem. 3, 138–149 ( 1996).
Liao, D., Hessler, N. A. & Malinow, R. Activation of postsynaptically silent synapses during pairing-induced LTP in CA1 region of hippocampal slice. Nature 375, 400–404 ( 1995).
O'Brien, R. J., Lau, L. F. & Huganir, R. L. Molecular mechanisms of glutamate receptor clustering at excitatory synapses. Curr. Opin. Neurobiol. 8, 364–369 (1998).
Katz, L. C. & Shatz, C. J. Synaptic activity and the construction of cortical circuits. Science 274, 1133– 1138 (1996).
Ruthazer, E. S. & Stryker, M. P. The role of activity in the development of long-range horizontal connections in area 17 of the ferret. J. Neurosci. 16, 7253– 7269 (1996).
Kim, H. G., Fox, K. & Connors, B. W. Properties of excitatory synaptic events in neurons of primary somatosensory cortex of neonatal rats. Cereb. Cortex 5, 148–157 ( 1995).
Isaac, J. T., Nicoll, R. A. & Malenka, R. C. Evidence for silent synapses: implications for the expression of LTP. Neuron 15, 427– 434 (1995).
Galli, L. & Maffei, L. Spontaneous impulse activity of rat retinal ganglion cells in prenatal life. Science 242 , 90–91 (1988).
Weliky, M. & Katz, L. C. Correlational structure of spontaneous neuronal activity in the developing lateral geniculate nucleus in vivo. Science 285, 599–604 ( 1999).
Bliss, T. V. & Collingridge, G. L. A synaptic model of memory: long-term potentiation in the hippocampus. Nature 361 , 31–39 (1993).
Zamanillo, D. et al. Importance of AMPA receptors for hippocampal synaptic plasticity but not for spatial learning. Science 284, 1805–1811 (1999).
Rao, A. & Craig, A. M. Activity regulates the synaptic localization of the NMDA receptor in hippocampal neurons. Neuron 19, 801–812 ( 1997).
Turrigiano, G. G., Leslie, K. R., Desai, N. S., Rutherford, L. C. & Nelson, S. B. Activity-dependent scaling of quantal amplitude in neocortical neurons. Nature 391 , 892–896 (1998).
Lissin, D. V. et al. Activity differentially regulates the surface expression of synaptic AMPA and NMDA glutamate receptors. Proc. Natl. Acad. Sci. USA 95, 7097–7102 ( 1998).
Gomperts, S. N., Carroll, R., Malenka, R. C. & Nicoll, R. A. Distinct roles for ionotropic and metabotropic glutamate receptors in the maturation of excitatory synapses. J. Neurosci. 20, 2229–2237 (2000).
Bekkers, J. M. & Stevens, C. F. Presynaptic mechanism for long-term potentiation in the hippocampus. Nature 346, 724–729 ( 1990).
Liu, S. Q. & Cull-Candy, S. G. Synaptic activity at calcium-permeable AMPA receptors induces a switch in receptor subtype. Nature 405, 454–458 (2000).
Zhu, J. J. Maturation of layer 5 neocortical pyramidal neurons: amplifying salient layer 1 and layer 4 inputs by Ca2+ action potentials in adult rat tuft dendrites. J. Physiol. (Lond.) 526, 571–587 (2000).
Acknowledgements
We thank Song-Hai Shi for help in cloning GluR2-GFP and GluR3-GFP constructs, Nancy Dawkins-Pisani and Tamara Howard for technical assistance, and H. Cline, J. Huang, Z. Mainen, E. Ruthazer and members of the Malinow laboratory for comments and discussions. This study was supported by the NIH, the Alzheimer's Association and the NARSAD Foundation.
Author information
Authors and Affiliations
Corresponding author
Supplementary information
Rights and permissions
About this article
Cite this article
Zhu, J., Esteban, J., Hayashi, Y. et al. Postnatal synaptic potentiation: Delivery of GluR4-containing AMPA receptors by spontaneous activity. Nat Neurosci 3, 1098–1106 (2000). https://doi.org/10.1038/80614
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/80614
This article is cited by
-
Aß Pathology and Neuron–Glia Interactions: A Synaptocentric View
Neurochemical Research (2023)
-
Filopodia are a structural substrate for silent synapses in adult neocortex
Nature (2022)
-
Magnesium Acts as a Second Messenger in the Regulation of NMDA Receptor-Mediated CREB Signaling in Neurons
Molecular Neurobiology (2020)
-
Stargazin and γ4 slow the channel opening and closing rates of GluA4 AMPA receptors
Scientific Reports (2019)
-
Palmitoylation-mediated synaptic regulation of AMPA receptor trafficking and function
Archives of Pharmacal Research (2019)