Cited by 46Neuroscience and Neuropharmacology ResearchMemory and Neural MechanismsProtein Kinase Regulation and GTPase Signaling

cAMP-Dependent Synaptic Plasticity at the Hippocampal Mossy Fiber Terminal

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Shahoha, Meishar, Cohen, Ronni, Ben-Simon, Yoav, Ashery, Uri·2022·Frontiers in Synaptic Neuroscience

Abstract

Cyclic adenosine monophosphate (cAMP) is a crucial second messenger involved in both pre- and postsynaptic plasticity in many neuronal types across species. In the hippocampal mossy fiber (MF) synapse, cAMP mediates presynaptic long-term potentiation and depression. The main cAMP-dependent signaling pathway linked to MF synaptic plasticity acts via the activation of the protein kinase A (PKA) molecular cascade. Accordingly, various downstream putative synaptic PKA target proteins have been linked to cAMP-dependent MF synaptic plasticity, such as synapsin, rabphilin, synaptotagmin-12, RIM1a, tomosyn, and P/Q-type calcium channels. Regulating the expression of some of these proteins alters synaptic release probability and calcium channel clustering, resulting in short- and long-term changes to synaptic efficacy. However, despite decades of research, the exact molecular mechanisms by which cAMP and PKA exert their influences in MF terminals remain largely unknown. Here, we review current knowledge of different cAMP catalysts and potential downstream PKA-dependent molecular cascades, in addition to non-canonical cAMP-dependent but PKA-independent cascades, which might serve as alternative, compensatory or competing pathways to the canonical PKA cascade. Since several other central synapses share a similar form of presynaptic plasticity with the MF, a better description of the molecular mechanisms governing MF plasticity could be key to understanding the relationship between the transcriptional and computational levels across brain regions.

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Crossref · 10.3389/fnsyn.2022.861215

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  • PKA is thought to phosphorylate several presynaptic target proteins, including synaptotagmin 12, tomosyn, rabphilins, SNAP 25, and RIMs.

    “PKA is thought to phosphorylate several presynaptic target proteins, including synaptotagmin 12, tomosyn, rabphilins, SNAP 25 (synaptosomal-associated protein of 25 kDa), and RIMs [92].”

    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 [92]

    The Molecular Mechanisms section identifies synaptotagmin-12, tomosyn-1, rabphilin and RIM1a as PKA targets or putative targets. It describes SNAP-25 as a protein that interacts with rabphilin, but does not say PKA phosphorylates SNAP-25. No page numbers are provided in our copy. (LLM, conf=0.88)

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Authors
Shahoha, M., Cohen, R., Ben-Simon, Y., & Ashery, U.
Affiliations
Tel Aviv University (IL)
Corresponding author
Ashery, Uri
Venue
Frontiers in Synaptic Neuroscience
Published
2022-04-04
Volume
14
Pages
861215-861215
ISSN
1663-3563 (ISSN-L)
OpenAlex
W4226264088
Cited by
46
References
186
Citations by year
2026: 7 · 2025: 9 · 2024: 19 · 2023: 9 · 2022: 2
FWCI
1.39
Type
journal article
Language
en
Open access
Locations
  • Frontiers in Synaptic Neuroscience (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders
Israel Science Foundation (2141/20)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
Keywords
cAMP signaling, protein kinase A, mossy fiber synapses, presynaptic plasticity, long-term potentiation, long-term depression, synapsin, tomosyn, P/Q-type calcium channels, hippocampus

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