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Long-term potentiation (LTP), an increase in synaptic efficacy following high-frequencystimulation, is widely considered a mechanism of learning. LTP involves local remodeling ofdendritic spines and synapses. Smooth endoplasmic reticulum (SER) and endosomal compartmentscould provide local stores of membrane and proteins, bypassing the distant Golgi apparatus. Totest this hypothesis, effects of LTP were compared to control stimulation in rat hippocampal areaCA1 at postnatal day 15 (P15). By two hours, small spines lacking SER increased after LTP, whereaslarge spines did not change in frequency, size, or SER content. Total SER volume decreased afterLTP consistent with transfer of membrane to the added spines. Shaft SER remained more abundantin spiny than aspiny dendritic regions, apparently supporting the added spines. Recyclingendosomes were elevated specifically in small spines after LTP. These findings suggest localsecretory trafficking contributes to LTP-induced synaptogenesis and primes the new spines forfuture plasticity.
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Synapse-specific structural plasticity that protects and refines local circuits during LTP and LTD
Synapses form trillions of connections in the brain. Long-term potentiation (LTP) and long-term depression (LTD) are cellular mechanisms vital for learning that modify the strength and structure of synapses. Three-dimensional reconstruction from serial section electron microscopy reveals three distinct pre- to post-synaptic arrangements: strong active zones (AZs) with tightly docked vesicles, weak AZs with loose or non-docked vesicles, and nascent zones (NZs) with a postsynaptic density but no presynaptic vesicles. Importantly, LTP can be temporarily saturated preventing further increases in synaptic strength. At the onset of LTP, vesicles are recruited to NZs, converting them to AZs. During recovery of LTP from saturation (1–4 h), new NZs form, especially on spines where AZs are most enlarged by LTP. Sentinel spines contain smooth endoplasmic reticulum (SER), have the largest synapses and form clusters with smaller spines lacking SER after LTP recovers. We propose a model whereby NZ plasticity provides synapse-specific AZ expansion during LTP and loss of weak AZs that drive synapse shrinkage during LTD. Spine clusters become functionally engaged during LTP or disassembled during LTD. Saturation of LTP or LTD probably acts to protect recently formed memories from ongoing plasticity and may account for the advantage of spaced over massed learning. This article is part of a discussion meeting issue ‘Long-term potentiation: 50 years on’.
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- Award ID(s):
- 2219979
- PAR ID:
- 10541430
- Publisher / Repository:
- Philosophical Transactions of the Royal Society B
- Date Published:
- Journal Name:
- Philosophical Transactions of the Royal Society B: Biological Sciences
- Volume:
- 379
- Issue:
- 1906
- ISSN:
- 0962-8436
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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- Free Publicly Accessible Full Text
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Accepted Manuscript
- Journal Article:
- https://doi.org/10.1098/rstb.2023.0224
