Kinetics of Releasable Synaptic Vesicles and Their Plastic Changes at Hippocampal Mossy Fiber Synapses
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Hippocampal mossy fiber boutons (hMFBs) are presynaptic terminals displaying various forms of synaptic plasticity. The presynaptic mechanisms underlying synaptic plasticity still remain poorly understood. Here, we have combined high temporal resolution measurements of presynaptic capacitance and excitatory postsynaptic currents (EPSCs) to measure the kinetics of exocytosis. In addition, total internal reflection fluorescence (TIRF) microscopy was employed to directly visualize dynamics of single synaptic vesicles adjacent to the plasma membrane at high spatial resolution. Readily releasable vesicles mostly consisted of already-tethered vesicles in the TIRF field. Vesicle replenishment had fast and slow phases, and TIRF imaging suggests that the fast phase depends on vesicle priming from already-tethered vesicles. Application of cyclic AMP (cAMP), a molecule crucial for LTP, mainly increases the vesicular release probability rather than the number of readily releasable vesicles or their replenishment rate, likely by changing the coupling between Ca 2+ channels and synaptic vesicles. Thus, we revealed dynamic properties of synaptic vesicles at hMFBs.
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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 [33]
Forskolin, an adenylyl cyclase activator, leads to marked chemical potentiation.
“Similarly, forskolin, an adenylyl cyclase (AC) activator, leads to marked chemical potentiation [29,32,33].”
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 [33]
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 [33]
Capacitance measurements from hippocampal mossy fiber terminals suggest that long depolarizing pulses release approximately 500-1,400 vesicles, corresponding to 17 to 48 vesicles per AZ.
“Capacitance measurements from hippocampal mossy fiber terminals suggest that long depolarizing pulses release approximately 500–1,400 vesicles, corresponding to 17 to 48 vesicles per AZ [33,86].”
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 [33]
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References 43 · Cited by 71
- Authors
- Midorikawa, M., & Sakaba, T.
- Affiliations
- Doshisha University (JP)
- Corresponding author
- Midorikawa, Mitsuharu
- Sakaba, Takeshi
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2017-12
- Volume
- 96
- Issue
- 5
- Pages
- 1033-1040.e3
- ISSN
- 0896-6273 (ISSN-L)
- OpenAlex
- W2766011755
- Cited by
- 71
- References
- 43
- Citations by year
- 2026: 4 · 2025: 5 · 2024: 10 · 2023: 13 · 2022: 8 · 2021: 7 · 2020: 8 · 2019: 9 · 2018: 6 · 2017: 1
- FWCI
- 3.21
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- Funders
- JSPS/MEXT KAKENHI (15K18346, 17K19466, 17H03548, 15K14321, 15H0426, 1, 17H05753)
- Takeda Science Foundation
- JSPS
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
- Keywords
- synaptic vesicle exocytosis, readily releasable vesicles, vesicle replenishment, vesicle tethering, vesicle priming, synaptic plasticity, long-term potentiation, cyclic AMP, excitatory postsynaptic currents, mossy fiber synapses, hippocampus, total internal reflection fluorescence microscopy
- MeSH terms
- Cyclic AMP, Animals, Exocytosis, Kinetics, Male, Synaptic Transmission, Neuronal Plasticity, Synapses, Synaptic Vesicles, Calcium Channels, Rats, Wistar, Pyramidal Cells, Patch-Clamp Techniques, Mossy Fibers, Hippocampal, Excitatory Postsynaptic Potentials, Rats
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