Presynaptic cAMP-PKA-mediated potentiation induces reconfiguration of synaptic vesicle pools and channel-vesicle coupling at hippocampal mossy fiber boutons

It is widely believed that information storage in neuronal circuits involves nanoscopic structural changes at synapses, resulting in the formation of synaptic engrams. However, direct evidence for this hypothesis is lacking. To test this conjecture, we combined chemical potentiation, functional anal...

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Published in:PLoS biology Vol. 22; no. 11; p. e3002879
Main Authors: Kim, Olena, Okamoto, Yuji, Kaufmann, Walter A., Brose, Nils, Shigemoto, Ryuichi, Jonas, Peter
Format: Journal Article
Language:English
Published: United States Public Library of Science 18.11.2024
Public Library of Science (PLoS)
Subjects:
Adenosine
Animals
Biology and Life Sciences
Brain research
Calcium channels
Calcium channels (voltage-gated)
Calcium Channels, N-Type - metabolism
Calcium ions
Cerebrospinal fluid
Colforsin - pharmacology
Coupling
Cyclic adenylic acid
Cyclic AMP - metabolism
Cyclic AMP-Dependent Protein Kinases - metabolism
Electron microscopy
Forskolin
Freeze-fracture
Functional analysis
Funding
Health aspects
Hippocampus
Hippocampus (Brain)
Hippocampus - cytology
Hippocampus - metabolism
Hippocampus - physiology
Human information processing
Information storage
Information storage and retrieval
Male
Medicine and Health Sciences
Mice
Microscopy
Mossy Fibers, Hippocampal - metabolism
Mossy Fibers, Hippocampal - physiology
Mossy Fibers, Hippocampal - ultrastructure
Nerve Tissue Proteins - metabolism
Neural circuitry
Neuronal Plasticity - physiology
Physical Sciences
Physiological aspects
Plastic memory
Potentiation
Presynapse
Presynaptic plasticity
Presynaptic Terminals - metabolism
Presynaptic Terminals - physiology
Protein kinase A
Protein kinases
Psychological aspects
Rats
Reconfiguration
Structural analysis
Synapses
Synaptic transmission
Synaptic Transmission - physiology
Synaptic Vesicles - metabolism
Synaptic Vesicles - physiology
Synaptic Vesicles - ultrastructure
Synaptogenesis
Vesicles
Germany
Puerto Rico
ISSN:1545-7885, 1544-9173, 1545-7885
Online Access:Get full text
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Summary:It is widely believed that information storage in neuronal circuits involves nanoscopic structural changes at synapses, resulting in the formation of synaptic engrams. However, direct evidence for this hypothesis is lacking. To test this conjecture, we combined chemical potentiation, functional analysis by paired pre-postsynaptic recordings, and structural analysis by electron microscopy (EM) and freeze-fracture replica labeling (FRL) at the rodent hippocampal mossy fiber synapse, a key synapse in the trisynaptic circuit of the hippocampus. Biophysical analysis of synaptic transmission revealed that forskolin-induced chemical potentiation increased the readily releasable vesicle pool size and vesicular release probability by 146% and 49%, respectively. Structural analysis of mossy fiber synapses by EM and FRL demonstrated an increase in the number of vesicles close to the plasma membrane and the number of clusters of the priming protein Munc13-1, indicating an increase in the number of both docked and primed vesicles. Furthermore, FRL analysis revealed a significant reduction of the distance between Munc13-1 and Ca V 2.1 Ca 2+ channels, suggesting reconfiguration of the channel-vesicle coupling nanotopography. Our results indicate that presynaptic plasticity is associated with structural reorganization of active zones. We propose that changes in potential nanoscopic organization at synaptic vesicle release sites may be correlates of learning and memory at a plastic central synapse.
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Current address: Institute of Molecular Biotechnology of the Austrian Academy of Science (IMBA), Vienna, Austria
Current address: Department of Cell Physiology, Graduate School of Medicine, Akita University, Akita, Japan
The authors have declared that no competing interests exist.
ISSN:1545-7885
1544-9173
1545-7885
DOI:10.1371/journal.pbio.3002879