Cited by 357Neuroscience and Neuropharmacology ResearchMemory and Neural MechanismsNitric Oxide and Endothelin Effects

Nitric Oxide Acts Directly in the Presynaptic Neuron to Produce Long-Term Potentiationin Cultured Hippocampal Neurons

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Arancio, Ottavio, Kiebler, Michael, Lee, C.Justin, Lev-Ram, Varda, Tsien, Roger Y, Kandel, Eric R, Hawkins, Robert D·1996·Cell

Abstract

Nitric oxide (NO) has been proposed to act as a retrograde messenger during long-term potentiation (LTP) in the CA1 region of hippocampus, but the inaccessibility of the presynaptic terminal has prevented a definitive test of this hypothesis. Because both sides of the synapse are accessible in cultured hippocampal neurons, we have used this preparation to investigate the role of NO. We examined LTP following intra- or extracellular application of an NO scavenger, an inhibitor of NO synthase, and a membrane-impermeant NO donor that releases NO only upon photolysis with UV light. Our results indicate that NO is produced in the postsynaptic neuron, travels through the extracellular space, and acts directly in the presynaptic neuron to produce long-term potentiation, supporting the hypothesis that NO acts as a retrograde messenger during LTP.

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Crossref · 10.1016/s0092-8674(00)81797-3

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  • Diverse mechanisms like retrograde signals using cannabinoids, or rapidly-diffusing gases such as nitric oxide, are among many that could enable learning rules that go beyond conventional conceptions of backpropagation.

    “Beyond dendritic computation, diverse mechanisms (Marblestone and Boyden, 2014) like retrograde (post-synaptic to pre-synaptic) signals using cannabinoids (Wilson and Nicoll, 2001), or rapidly-diffusing gases such as nitric oxide (Arancio et al., 1996), are among many that could enable learning rules that go beyond conventional conceptions of backpropagation.”

    From Toward an integration of deep learning and neuroscience (2016) · cites this paper as Arancio et al., 1996

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Authors
Arancio, O., Kiebler, M., Lee, C. J., Lev-Ram, V., Tsien, R. Y., Kandel, E. R., & Hawkins, R. D.
Affiliations
  • Columbia University (US)
  • Howard Hughes Medical Institute (US)
  • New York State Psychiatric Institute (US)
Corresponding author
Hawkins, Robert D
Venue
Cell
Publisher
Elsevier BV
Published
1996-12
Volume
87
Issue
6
Pages
1025-1035
ISSN
0092-8674 (ISSN-L)
OpenAlex
W2102133195
Cited by
357
References
30
Citations by year
2026: 5 · 2025: 3 · 2024: 7 · 2023: 8 · 2022: 10 · 2021: 7 · 2020: 8 · 2019: 8 · 2018: 7 · 2017: 7 · 2016: 6 · 2015: 5 · 2014: 14 · 2013: 13 · 2012: 11
FWCI
8.37
Type
journal article
Language
en
Open access
Locations
  • Cell (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
Funders
National Institute of Mental Health (P50MH050733, MH-50733)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
  • Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
Keywords
nitric oxide, long-term potentiation, retrograde signaling, presynaptic neurons, hippocampal neurons, NO synthase inhibition, NO scavenger, CA1 region
MeSH terms
Animals, Cells, Cultured, Extracellular Space, Fluorescent Antibody Technique, Hippocampus, Membrane Potentials, Methemoglobin, Microinjections, Myoglobin, Neurons, Nitric Oxide, Photolysis, Tetanus Toxin, Ultraviolet Rays, Rats, Sprague-Dawley, Presynaptic Terminals, Long-Term Potentiation, Neurotransmitter Agents, Nitric Oxide Synthase, Rats

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