cAMP contributes to mossy fiber LTP by initiating both a covalently mediated early phase and macromolecular synthesis-dependent late phase
Abstract
Memory storage has a short-term phase that depends on preexisting proteins and a long-term phase that requires new protein and RNA synthesis. Hippocampal long-term potentiation (LTP) is thought to contribute to memory storage. Consistent with this idea, a cellular representation of these phases has been demonstrated in NMDA receptor-dependent LTP. By contrast, little is known about the NMDA receptor-independent LTP of the mossy fiber pathway. We find that mossy fiber LTP also has phases. Only late phase is blocked by protein and RNA synthesis inhibitors, but both phases are blocked by inhibitors of cAMP-dependent protein kinase, and both are stimulated by forskolin and Sp-cAMPS. During early phase, paired-pulse facilitation is occluded. This occlusion decays with the onset of late phase, consistent with its using a different mechanism. Thus, although Schaffer collateral and mossy fiber pathways use very different mechanisms for early phase, both use a cAMP-mediated mechanism for late phase.
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Forskolin is a widely used adenylyl cyclase activator.
“To maximally activate the cAMP pathway, we applied forskolin, a widely used AC activator [28–31,33,48].”
From Presynaptic cAMP-PKA-mediated potentiation induces reconfiguration of synaptic vesicle pools and channel-vesicle coupling at hippocampal mossy fiber boutons (2024) · cites this paper as [28]
High-frequency stimulation induces several cAMP-dependent forms of presynaptic plasticity.
“For example, high-frequency stimulation (HFS) induces several cyclic adenosine monophosphate (cAMP)-dependent forms of presynaptic plasticity [21,28–33].”
From Presynaptic cAMP-PKA-mediated potentiation induces reconfiguration of synaptic vesicle pools and channel-vesicle coupling at hippocampal mossy fiber boutons (2024) · cites this paper as [28]
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“For example, high-frequency stimulation (HFS) induces several cyclic adenosine monophosphate (cAMP)-dependent forms of presynaptic plasticity [21,28–33].”
- Authors
- Huang, Y.-Y., Li, X.-C., & Kandel, E. R.
- Affiliations
- Howard Hughes Medical Institute (US)
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 1994-10
- Volume
- 79
- Issue
- 1
- Pages
- 69-79
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2008792865
- Cited by
- 490
- References
- 5
- Citations by year
- 2026: 1 · 2025: 5 · 2024: 6 · 2023: 4 · 2022: 6 · 2021: 8 · 2020: 3 · 2019: 9 · 2018: 6 · 2017: 9 · 2016: 8 · 2015: 12 · 2014: 9 · 2013: 12 · 2012: 12
- FWCI
- 11.75
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5p01gm032099-14)
- National Institute of General Medical Sciences (GM 32099)
- 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
- cyclic AMP, protein kinase A, late-phase LTP, paired-pulse facilitation, protein synthesis, RNA synthesis, hippocampus, memory storage, forskolin
- MeSH terms
- Cyclic AMP, Animals, Anisomycin, Dactinomycin, Electric Stimulation, Colforsin, Hippocampus, Nerve Fibers, Nerve Tissue Proteins, Retention, Psychology, RNA, Messenger, Thionucleotides, Second Messenger Systems, Receptors, N-Methyl-D-Aspartate, Rats, Sprague-Dawley, Long-Term Potentiation, Protein Kinase Inhibitors, Rats
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