Evidence for silent synapses: Implications for the expression of LTP
Open accessAbstract
Recent work has suggested that some proportion of excitatory synapses on hippocampal CA1 pyramidal cells that express NMDA receptors (NMDARs) may not express functional AMPA receptors (AMPARs), thus making these synapses silent at the resting membrane potential. In agreement with this hypothesis, we demonstrate here that it is possible to stimulate synapses that yield no detectable excitatory postsynaptic currents (EPSCs) when the cell is held at -60 mV; yet at positive holding potentials (+30 to +60 mV), EPSCs can be elicited that are completely blocked by the NMDAR antagonist, D-APV. When these functionally silent synapses are subjected to an LTP induction protocol, EPSCs mediated by AMPARs appear and remain for the duration of the experiment. This conversion of silent synapses to functional synapses is blocked by D-APV. These results suggest that LTP may involve modification of AMPARs that, prior to LTP, were either not present in the postsynaptic membrane or electrophysiologically silent. This mechanism may account for several experimental results previously attributed to presynaptic changes in quantal content.
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After application of an LTP induction protocol, silent synapses become functional because of the insertion of AMPARs into their postsynaptic membrane.
“After the application of an LTP induction protocol, these synapses “wake up” and become functional because of the insertion of AMPARs into their postsynaptic membrane (Isaac et al. 1995;Liao et al. 1995).”
From NMDA receptor-dependent long-term potentiation and long-term depression (LTP/LTD). (2012) · cites this paper as Isaac et al. 1995
LTP-producing stimuli cause rapid accumulation of AMPARs at silent synapses, referred to as unsilencing.
“LTP-producing stimuli cause a rapid accumulation of AMPARs referred to as “unsilencing” (238–241).”
From Synaptic memory and CaMKII (2023) · cites this paper as [238]
There is a population of synapses that lack AMPARs but have a normal complement of NMDARs, referred to as silent synapses.
“First, there is a population of synapses that lack AMPARs but have a normal complement of NMDARs and are referred to as “silent synapses.””
From Synaptic memory and CaMKII (2023) · cites this paper as [238]
LTP-induced unsilencing of synapses indicates that LTP can be all or none.
“The LTP-induced unsilencing of synapses (238–240) certainly indicates that LTP can be all or none.”
From Synaptic memory and CaMKII (2023) · cites this paper as [238]
Synapses with few, if any, AMPARs, referred to as silent synapses, form a distinct anatomical class referred to as filopodial synapses, in contrast to classical spine synapses.
“Recent work has shown that synapses with few, if any, AMPARs, referred to as silent synapses (238, 239), form a distinct anatomical class referred to as filopodial synapses, in contrast to classical spine synapses (240).”
From Synaptic memory and CaMKII (2023) · cites this paper as [238]
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- Authors
- Isaac, J. T. R., Nicoll, R. A., & Malenka, R. C.
- Affiliations
- University of California, San Francisco (US)
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 1995-08
- Volume
- 15
- Issue
- 2
- Pages
- 427-434
- ISSN
- 0896-6273 (ISSN-L)
- OpenAlex
- W2106414999
- Cited by
- 1,233
- References
- 3
- Citations by year
- 2026: 13 · 2025: 16 · 2024: 20 · 2023: 20 · 2022: 20 · 2021: 30 · 2020: 38 · 2019: 23 · 2018: 32 · 2017: 34 · 2016: 35 · 2015: 38 · 2014: 35 · 2013: 38 · 2012: 39
- FWCI
- 29.18
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Keywords
- silent synapses, long-term potentiation, AMPA receptors, NMDA receptor, CA1 pyramidal neurons, excitatory postsynaptic currents, D-APV, holding potential, synaptic plasticity
- MeSH terms
- Action Potentials, Animals, Hippocampus, Models, Neurological, Synapses, 2-Amino-5-phosphonovalerate, Receptors, N-Methyl-D-Aspartate, Rats, Sprague-Dawley, Long-Term Potentiation, Receptors, AMPA, Rats
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