Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.


Sci. STKE, 10 October 2006
Vol. 2006, Issue 356, p. re11
[DOI: 10.1126/stke.3562006re11]


A Unified Model of the Presynaptic and Postsynaptic Changes During LTP at CA1 Synapses

John Lisman1* and Sridhar Raghavachari2*

1Department of Biology, Brandeis University, Waltham, MA 02454, USA.
2Box 3209, Department of Neurobiology, Duke University Medical Center, Durham, NC 27710, USA.

Abstract: Long-term potentiation (LTP) has been studied extensively at CA1 synapses of the hippocampus, and there is evidence implicating both postsynaptic and presynaptic changes in this process. These changes include (i) addition of AMPA channels to the extrasynaptic membrane and diffusional equilibrium of extrasynaptic receptors with synaptic receptors, (ii) sudden addition of AMPA channels to the synapse in large groups, (iii) a change in the mode of glutamate release (presumably from kiss-and-run to full fusion), and (iv) a delayed increase in the number of vesicles released. However, it remains unclear whether (or how) these changes work together. We have incorporated all of these processes into a structural model of the synapse. We propose that the synapse is composed of transsynaptic modules that function quasi-independently in AMPA-mediated transmission. Under basal conditions, synapses are partially silent; some modules are AMPA-silent (but contribute to NMDA-mediated transmission), whereas others are functional (and contribute to both AMPA- and NMDA-mediated transmission). During LTP, there is both a rapid change in the mode of vesicle fusion and a rapid insertion of a postsynaptic complex (a hyperslot) containing many proteins (slots) capable of binding AMPA channels. The combined effect of these pre- and postsynaptic changes is to convert AMPA-silent modules into functional modules. Slot filling is transiently enhanced by a rapid increase in extrasynaptic GluR1, a form of the AMPA-type receptor. A slower transsynaptic growth process adds AMPA-silent modules to the synapse, enhancing the number of vesicles released and thereby enhancing the NMDA response. This model accounts for a broad range of data, including the LTP-induced changes in quantal parameters. The model also provides a coherent explanation for the diverse effects of GluR1 knockout on basal transmission, LTP, and distance-dependent scaling.

*Corresponding author. E-mail, lisman{at}; sri{at}

Citation: J. Lisman, S. Raghavachari, A Unified Model of the Presynaptic and Postsynaptic Changes During LTP at CA1 Synapses. Sci. STKE 2006, re11 (2006).

Read the Full Text

The expression of long-term potentiation: reconciling the preists and the postivists.
M. J. MacDougall and A. Fine (2013)
Phil Trans R Soc B 369, 20130135
   Abstract »    Full Text »    PDF »
Two sides to long-term potentiation: a view towards reconciliation.
Z. Padamsey and N. Emptage (2013)
Phil Trans R Soc B 369, 20130154
   Abstract »    Full Text »    PDF »
ErbB4 reduces synaptic GABAA currents independent of its receptor tyrosine kinase activity.
R. M. Mitchell, M. J. Janssen, I. Karavanova, D. Vullhorst, K. Furth, A. Makusky, S. P. Markey, and A. Buonanno (2013)
PNAS 110, 19603-19608
   Abstract »    Full Text »    PDF »
How to Scale Down Postsynaptic Strength.
V. Tatavarty, Q. Sun, and G. G. Turrigiano (2013)
J. Neurosci. 33, 13179-13189
   Abstract »    Full Text »    PDF »
Super-Resolution Imaging Reveals That AMPA Receptors Inside Synapses Are Dynamically Organized in Nanodomains Regulated by PSD95.
D. Nair, E. Hosy, J. D. Petersen, A. Constals, G. Giannone, D. Choquet, and J.-B. Sibarita (2013)
J. Neurosci. 33, 13204-13224
   Abstract »    Full Text »    PDF »
Matched Pre- and Post-Synaptic Changes Underlie Synaptic Plasticity over Long Time Scales.
A. Loebel, J.-V. Le Be, M. J. E. Richardson, H. Markram, and A. V. M. Herz (2013)
J. Neurosci. 33, 6257-6266
   Abstract »    Full Text »    PDF »
Glutamate Receptor 1 Phosphorylation at Serine 831 and 845 Modulates Seizure Susceptibility and Hippocampal Hyperexcitability after Early Life Seizures.
S. N. Rakhade, E. F. Fitzgerald, P. M. Klein, C. Zhou, H. Sun, R. L. Huganir, and F. E. Jensen (2012)
J. Neurosci. 32, 17800-17812
   Abstract »    Full Text »    PDF »
Studying Signal Transduction in Single Dendritic Spines.
R. Yasuda (2012)
Cold Spring Harb Perspect Biol 4, a005611
   Abstract »    Full Text »    PDF »
Glutamate Dysfunction in Hippocampus: Relevance of Dentate Gyrus and CA3 Signaling.
C. A. Tamminga, S. Southcott, C. Sacco, A. D. Wagner, and S. Ghose (2012)
Schizophr Bull 38, 927-935
   Abstract »    Full Text »    PDF »
A role for {alpha}-adducin (ADD-1) in nematode and human memory.
V. Vukojevic, L. Gschwind, C. Vogler, P. Demougin, D. J.-F. de Quervain, A. Papassotiropoulos, and A. Stetak (2012)
EMBO J. 31, 1453-1466
   Abstract »    Full Text »    PDF »
Unified quantitative model of AMPA receptor trafficking at synapses.
K. Czondor, M. Mondin, M. Garcia, M. Heine, R. Frischknecht, D. Choquet, J.-B. Sibarita, and O. R. Thoumine (2012)
PNAS 109, 3522-3527
   Abstract »    Full Text »    PDF »
Trafficking of gap junction channels at a vertebrate electrical synapse in vivo.
C. E. Flores, S. Nannapaneni, K. G. V. Davidson, T. Yasumura, M. V. L. Bennett, J. E. Rash, and A. E. Pereda (2012)
PNAS 109, E573-E582
   Abstract »    Full Text »    PDF »
Presynaptic LTP and LTD of Excitatory and Inhibitory Synapses.
P. E. Castillo (2012)
Cold Spring Harb Perspect Biol 4, a005728
   Abstract »    Full Text »    PDF »
RNA Binding Proteins Accumulate at the Postsynaptic Density with Synaptic Activity.
G. Zhang, T. A. Neubert, and B. A. Jordan (2012)
J. Neurosci. 32, 599-609
   Abstract »    Full Text »    PDF »
Subsynaptic AMPA Receptor Distribution Is Acutely Regulated by Actin-Driven Reorganization of the Postsynaptic Density.
J. M. Kerr and T. A. Blanpied (2012)
J. Neurosci. 32, 658-673
   Abstract »    Full Text »    PDF »
PSD-95 Is Required to Sustain the Molecular Organization of the Postsynaptic Density.
X. Chen, C. D. Nelson, X. Li, C. A. Winters, R. Azzam, A. A. Sousa, R. D. Leapman, H. Gainer, M. Sheng, and T. S. Reese (2011)
J. Neurosci. 31, 6329-6338
   Abstract »    Full Text »    PDF »
Regulation of Neuronal Function by Ras-GRF Exchange Factors.
L. A. Feig (2011)
Genes & Cancer 2, 306-319
   Abstract »    Full Text »    PDF »
The h Current Is a Candidate Mechanism for Regulating the Sliding Modification Threshold in a BCM-Like Synaptic Learning Rule.
R. Narayanan and D. Johnston (2010)
J Neurophysiol 104, 1020-1033
   Abstract »    Full Text »    PDF »
Persistence of Coordinated Long-Term Potentiation and Dendritic Spine Enlargement at Mature Hippocampal CA1 Synapses Requires N-Cadherin.
O. Bozdagi, X.-b. Wang, J. S. Nikitczuk, T. R. Anderson, E. B. Bloss, G. L. Radice, Q. Zhou, D. L. Benson, and G. W. Huntley (2010)
J. Neurosci. 30, 9984-9989
   Abstract »    Full Text »    PDF »
Perisynaptic GluR2-lacking AMPA receptors control the reversibility of synaptic and spines modifications.
Y. Yang, X.-b. Wang, and Q. Zhou (2010)
PNAS 107, 11999-12004
   Abstract »    Full Text »    PDF »
Activity Pattern-Dependent Long-Term Potentiation in Neocortex and Hippocampus of GluA1 (GluR-A) Subunit-Deficient Mice.
M. C. Frey, R. Sprengel, and T. Nevian (2009)
J. Neurosci. 29, 5587-5596
   Abstract »    Full Text »    PDF »
Picomolar Amyloid-{beta} Positively Modulates Synaptic Plasticity and Memory in Hippocampus.
D. Puzzo, L. Privitera, E. Leznik, M. Fa, A. Staniszewski, A. Palmeri, and O. Arancio (2008)
J. Neurosci. 28, 14537-14545
   Abstract »    Full Text »    PDF »
Postsynaptic Action Potentials Are Required for Nitric-Oxide-Dependent Long-Term Potentiation in CA1 Neurons of Adult GluR1 Knock-Out and Wild-Type Mice.
K. G. Phillips, N. R. Hardingham, and K. Fox (2008)
J. Neurosci. 28, 14031-14041
   Abstract »    Full Text »    PDF »
Kalirin-7 Is Required for Synaptic Structure and Function.
X.-M. Ma, D. D. Kiraly, E. D. Gaier, Y. Wang, E.-J. Kim, E. S. Levine, B. A. Eipper, and R. E. Mains (2008)
J. Neurosci. 28, 12368-12382
   Abstract »    Full Text »    PDF »
Age-dependent requirement of AKAP150-anchored PKA and GluR2-lacking AMPA receptors in LTP.
Y. Lu, M. Allen, A. R. Halt, M. Weisenhaus, R. F. Dallapiazza, D. D. Hall, Y. M. Usachev, G. S. McKnight, and J. W. Hell (2007)
EMBO J. 26, 4879-4890
   Abstract »    Full Text »    PDF »
Slow Presynaptic and Fast Postsynaptic Components of Compound Long-Term Potentiation.
I. T. Bayazitov, R. J. Richardson, R. G. Fricke, and S. S. Zakharenko (2007)
J. Neurosci. 27, 11510-11521
   Abstract »    Full Text »    PDF »

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882