Activation of postsynaptically silent synapses during pairing-induced LTP in CA1 region of hippocampal slice
Abstract
Long-term potentiation (LTP) is an enhancement of synaptic strength that can be produced by pairing of presynaptic activity with postsynaptic depolarization. LTP in the hippocampus has been extensively studied as a cellular model of learning and memory, but the nature of the underlying synaptic modification remains elusive, partly because our knowledge of central synapses is still limited. One proposal is that the modification is postsynaptic, and that synapses expressing only NMDA (N-methyl-D-aspartate) receptors before potentiation are induced by LTP to express functional AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazoleproprionate) receptors. Here we report that a high proportion of synapses in hippocampal area CA1 transmit with NMDA receptors but not AMPA receptors, making these synapses effectively non-functional at normal resting potentials. These silent synapses acquire AMPA-type responses following LTP induction. Our findings challenge the view that LTP in CA1 involves a presynaptic modification, and suggest instead a simple postsynaptic mechanism for both induction and expression of LTP.
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Expression of AMPARs on the postsynaptic membrane is induced by NMDAR-mediated long term potentiation (LTP).
“Expression of AMPARs on the postsynaptic membrane is induced by NMDAR-mediated long term potentiation (LTP), the same mechanism originally described in hippocampus for learning and memory.73, 74, 75, 76”
From A role for synaptic plasticity in the adolescent development of executive function (2013) · cites this paper as [75]
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 Liao 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 [239]
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 [239]
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 [239]
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 [239]
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- Authors
- Liao, D., Hessler, N. A., & Malinow, R.
- Affiliations
- Cold Spring Harbor Laboratory (US)
- University of Iowa (US)
- Venue
- Nature
- Published
- 1995-06
- Volume
- 375
- Issue
- 6530
- Pages
- 400-404
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2051378734
- Cited by
- 1,365
- References
- 31
- Citations by year
- 2026: 11 · 2025: 18 · 2024: 27 · 2023: 26 · 2022: 23 · 2021: 25 · 2020: 36 · 2019: 29 · 2018: 36 · 2017: 35 · 2016: 29 · 2015: 35 · 2014: 31 · 2013: 42 · 2012: 37
- FWCI
- 35.49
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Cold Spring Harbor Laboratory Institutional Repository (Cold Spring Harbor Laboratory) (acceptedVersion)
- Funders
- National Institutes of Health (5r29mh049159-06)
- National Institute of Mental Health (R29MH49159)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural dynamics and brain function
- Keywords
- long-term potentiation, silent synapses, NMDA receptor, AMPA receptors, hippocampal CA1, paired-pulse stimulation, synaptic transmission, learning and memory
- MeSH terms
- Animals, Electric Stimulation, Hippocampus, Synapses, Receptors, N-Methyl-D-Aspartate, Long-Term Potentiation, Receptors, AMPA, Neurotransmitter Agents, Patch-Clamp Techniques, Rats, In Vitro Techniques
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