Postnatal synaptic potentiation: delivery of GluR4-containing AMPA receptors by spontaneous activity
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.
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GRIA4 encodes an AMPA-sensitive glutamate receptor that functions as a ligand-gated ion channel and mediates synaptic transmission and neuroplasticity.
“For instance, GRIA4 encodes an AMPA-sensitive glutamate receptor that functions as a ligand-gated ion channel and mediates synaptic transmission and neuroplasticity (Zhu et al. 2000).”
From Genomic Analyses Unveil Helmeted Guinea Fowl (<i>Numida meleagris</i>) Domestication in West Africa (2021) · cites this paper as Zhu et al. 2000
NMDARs are localized very early to the postsynaptic membrane, but transition to a more mature synapse state is characterized by recruitment of AMPARs to the synapse.
“N-methyl-D-aspartate receptors (NMDAR) are localized very early to the postsynaptic membrane, but transition to a more mature synapse state is characterized by recruitment of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors (AMPAR) to the synapse.71, 72, 73, 74”
From A role for synaptic plasticity in the adolescent development of executive function (2013) · cites this paper as [74]
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 [74]
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- Authors
- Zhu, J. J., Esteban, J. A., Hayashi, Y., & Malinow, R.
- Affiliations
- Cold Spring Harbor Laboratory (US)
- Massachusetts Institute of Technology (US)
- Corresponding author
- Malinow, Roberto
- Venue
- Nature Neuroscience
- Published
- 2000-11
- Volume
- 3
- Issue
- 11
- Pages
- 1098-1106
- ISSN
- 1097-6256 (ISSN-L)
- 1546-1726
- OpenAlex
- W1544008935
- Cited by
- 437
- References
- 43
- Citations by year
- 2026: 3 · 2025: 10 · 2024: 9 · 2023: 5 · 2022: 9 · 2021: 14 · 2020: 15 · 2019: 8 · 2018: 18 · 2017: 11 · 2016: 10 · 2015: 13 · 2014: 16 · 2013: 12 · 2012: 16
- FWCI
- 8.51
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Nature Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Cold Spring Harbor Laboratory Institutional Repository (Cold Spring Harbor Laboratory) (acceptedVersion)
- DIGITAL.CSIC (Spanish National Research Council (CSIC)) (submittedVersion)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Keywords
- GluR4, GluR2, AMPA receptor trafficking, spontaneous neuronal activity, hippocampus, NMDA receptor, CaMKII, NSF, synaptic transmission, circuit formation
- MeSH terms
- Animals, Cell Line, Hippocampus, Synaptic Transmission, Synapses, Receptors, AMPA, Excitatory Postsynaptic Potentials, Rats
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