A presynaptic locus for long-term potentiation of elementary synaptic transmission at mossy fiber synapses in culture.
Open accessAbstract
The complex circuitry of the CA3 region and the abundance of collateral connections has made it difficult to study the mossy fiber pathway in hippocampal slices and therefore to establish the site of expression of long-term potentiation at these synapses. Using a novel cell culture system, we have produced long-term potentiation of the elementary synaptic connections on single CA3 pyramidal neurons following tetanic stimulation of individual dentate gyrus granule cells. As is the case for the hippocampal slice, this potentiation was independent of N-methyl-D-aspartate receptor activation, was simulated by application of forskolin, and its induction did not require any modulatory input. The increase in synaptic strength was accompanied by a reduction in the number of failures of transmission and by an increase in the coefficient of variation of the responses and was prevented by presynaptic injection of an inhibitor of protein kinase A. These findings show that mossy fiber long-term potentiation has a presynaptic locus and that its expression is dependent on protein kinase A.
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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 [31]
The Abstract reports applying forskolin to simulate mossy-fiber potentiation and links that potentiation to protein kinase A. It does not identify forskolin as an adenylyl cyclase activator or say that its use is widespread; searches for those terms found no supporting passage in our copy. (LLM, conf=0.78)
Experimental — accuracy not yet measuredHigh-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 [31]
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“To maximally activate the cAMP pathway, we applied forskolin, a widely used AC activator [28–31 ,33 ,48 To determine the locus of chemical potentiation, we analyzed the paired-pulse ratio (PPR; EPSC 2 /EPSC 1 ; Fig 1D).”
- Authors
- López-García, J. C., Arancio, O., Kandel, E. R., & Baranes, D.
- Affiliations
- Howard Hughes Medical Institute, College of Physicians and Surgeons of Columbia University, NY 10032, USA.
- Howard Hughes Medical Institute (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 1996-05-14
- Volume
- 93
- Issue
- 10
- Pages
- 4712-4717
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC39344
- OpenAlex
- W2030749284
- Cited by
- 36
- References
- 2
- Citations by year
- 2024: 1 · 2023: 1 · 2021: 1 · 2016: 1 · 2014: 1 · 2012: 2
- FWCI
- 0.81
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Howard Hughes Medical Institute
- National Institute of General Medical Sciences (GM30299)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural dynamics and brain function
- Keywords
- long-term potentiation, mossy fiber synapses, presynaptic plasticity, CA3 pyramidal cells, dentate gyrus granule cells, protein kinase A, forskolin, coefficient of variation, hippocampus
- MeSH terms
- Animals, Cells, Cultured, Dynorphins, Electrophysiology, Glutamine, Hippocampus, Synaptic Transmission, Synapses, Receptors, N-Methyl-D-Aspartate, Long-Term Potentiation, Pyramidal Cells, Dentate Gyrus, Rats
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