Mechanisms underlying induction of homosynaptic long-term depression in area CA1 of the hippocampus
Abstract
The mechanisms responsible for long-lasting, activity-dependent decreases in synaptic efficacy are not well understood. We have examined the initial steps required for the induction of long-term depression (LTD) in CA1 pyramidal cells by repetitive low frequency (1 Hz) synaptic stimulation. This form of LTD was synapse specific, was saturable, and required activation of post-synaptic NMDA receptors. Loading CA1 cells with the Ca2+ chelator BAPTA prevented LTD, whereas lowering extracellular Ca2+ resulted in the induction of LTD by stimulation that previously elicited long-term potentiation. Following LTD, synaptic strength could be increased to its original maximal level, indicating that LTD is reversible and not due to deterioration of individual synapses. Induction of homosynaptic LTD therefore requires an NMDA receptor-dependent change in postsynaptic Ca2+ which may be distinct from that required for long-term potentiation.
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Low-frequency prolonged synaptic stimulation evokes an NMDAR-dependent LTD.
“Low-frequency prolonged synaptic stimulation evokes an NMDAR-dependent LTD (374, 393), and blockade of phosphatases by Calyculin A enhances AMPAR responses but not NMDAR responses (Ref. 394, but see Ref. 395).”
From Synaptic memory and CaMKII (2023) · cites this paper as [393]
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Background
- Authors
- Mulkey, R. M., & Malenka, R. C.
- Affiliations
- University of California, San Francisco (US)
- ORCID
- Malenka, Robert C.
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 1992-11
- Volume
- 9
- Issue
- 5
- Pages
- 967-975
- ISSN
- 0896-6273 (ISSN-L)
- OpenAlex
- W2046388858
- Cited by
- 1,113
- References
- 2
- Citations by year
- 2026: 7 · 2025: 22 · 2024: 19 · 2023: 19 · 2022: 22 · 2021: 22 · 2020: 22 · 2019: 23 · 2018: 28 · 2017: 16 · 2016: 32 · 2015: 28 · 2014: 22 · 2013: 36 · 2012: 30
- FWCI
- 19.56
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r29mh045334-05)
- National Institute of Mental Health (MH45334, MH00942)
- National Institute of Neurological Disorders and Stroke (T32NS007067, NS 07067)
- 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
- CA1 pyramidal neurons, hippocampus, NMDA receptor, calcium signaling, BAPTA, extracellular calcium, long-term potentiation, synaptic plasticity
- MeSH terms
- Animals, Calcium, Chelating Agents, Electric Stimulation, Hippocampus, Membrane Potentials, Synapses, Receptors, N-Methyl-D-Aspartate, Rats, Sprague-Dawley, Rats
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