Selective acquisition of AMPA receptors over postnatal development suggests a molecular basis for silent synapses
Abstract
Early in postnatal development, glutamatergic synapses transmit primarily through NMDA receptors. As development progresses, synapses acquire AMPA receptor function. The molecular basis of these physiological observations is not known. Here we examined single excitatory synapses with immunogold electron-microscopic analysis of AMPA and NMDA receptors along with electrophysiological measurements. Early in postnatal development, a significant fraction of excitatory synapses had NMDA receptors and lacked AMPA receptors. As development progressed, synapses acquired AMPA receptors with little change in NMDA receptor number. Thus, synapses with NMDA receptors but no AMPA receptors can account for the electrophysiologically observed 'silent synapse'.
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These data conform with the development of AMPA receptor immunoreactivity in CA1 pyramidal neurons.
“These data conform with the development of AMPA receptor immunoreactivity in CA1 pyramidal neurons35.”
From Dendritic spine geometry is critical for AMPA receptor expression in hippocampal CA1 pyramidal neurons (2001) · cites this paper as [35]
In early development, many synapse types are morphologically intact and can release glutamate, but most glutamatergic postsynapses on excitatory neurons are not yet functional.
“While many synapse types are morphologically intact and capable of releasing glutamate, the majority of glutamaterigic post-synapses on excitatory neurons are not yet functional (Ashby and Isaac, 2011; Isaac et al., 1997; Petralia et al., 1999).”
From Pathogenic SYNGAP1 Mutations Impair Cognitive Development by Disrupting Maturation of Dendritic Spine Synapses (2012) · cites this paper as Petralia et al., 1999
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- Authors
- Petralia, R. S., Esteban, J. A., Wang, Y. –., Partridge, J. G., Zhao, H. –., Wenthold, R. J., & Malinow, R.
- Affiliations
- National Institutes of Health (US)
- Cold Spring Harbor Laboratory (US)
- Corresponding author
- Malinow, R.
- Venue
- Nature Neuroscience
- Published
- 1999-01
- Volume
- 2
- Issue
- 1
- Pages
- 31-36
- ISSN
- 1097-6256 (ISSN-L)
- 1546-1726
- DOI
- 10.1038/4532
- OpenAlex
- W2129766810
- Cited by
- 496
- References
- 32
- Citations by year
- 2025: 4 · 2024: 7 · 2023: 8 · 2022: 9 · 2021: 8 · 2020: 11 · 2019: 11 · 2018: 13 · 2017: 6 · 2016: 9 · 2015: 7 · 2014: 14 · 2013: 8 · 2012: 21
- FWCI
- 17.50
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Cold Spring Harbor Laboratory Institutional Repository (Cold Spring Harbor Laboratory) (acceptedVersion)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Keywords
- AMPA receptors, NMDA receptor, silent synapses, glutamatergic synapses, receptor trafficking, excitatory synapses, synapse maturation
- MeSH terms
- Aging, Animals, Animals, Newborn, Electrophysiology, Hippocampus, Immunohistochemistry, Male, Microscopy, Electron, Synapses, Receptors, N-Methyl-D-Aspartate, Rats, Sprague-Dawley, Receptors, AMPA, Rats
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