Cited by 740Alzheimer's disease research and treatmentsNeuroscience and Neuropharmacology ResearchMemory and Neural Mechanisms

Picomolar Amyloid-β Positively Modulates Synaptic Plasticity and Memory in Hippocampus

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Puzzo, Daniela, Privitera, Lucia, Leznik, Elena, Fà, Mauro, Staniszewski, Agnieszka, Palmeri, Agostino, Arancio, Ottavio·2008·The Journal of Neuroscience

Abstract

Amyloid-β (Aβ) peptides are produced in high amounts during Alzheimer's disease, causing synaptic and memory dysfunction. However, they are also released in lower amounts in normal brains throughout life during synaptic activity. Here we show that low picomolar concentrations of a preparation containing both Aβ 42 monomers and oligomers cause a marked increase of hippocampal long-term potentiation, whereas high nanomolar concentrations lead to the well established reduction of potentiation. Picomolar levels of Aβ 42 also produce a pronounced enhancement of both reference and contextual fear memory. The mechanism of action of picomolar Aβ 42 on both synaptic plasticity and memory involves α7-containing nicotinic acetylcholine receptors. These findings strongly support a model for Aβ effects in which low concentrations play a novel positive, modulatory role on neurotransmission and memory, whereas high concentrations play the well known detrimental effect culminating in dementia.

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Crossref · 10.1523/jneurosci.2692-08.2008

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  • Aβ plays a role in synaptic transmission and is involved in learning and memory formation.

    “studies that shed light on the physiological role of Aβ in non-diseased brains show that Aβ plays a role in synaptic transmission and is involved in learning and memory formation [18–22].”
  • Other studies injected picomolar concentrations of Aβ peptides into mice, which also significantly enhanced synaptic plasticity and memory formation.

    “To address this concern, other studies injected picomolar concentrations of Aβ peptides into the mice, which also significantly enhanced synaptic plasticity and memory formation.394”
  • At sub-nanomolar doses, Aβ markedly enhances LTP, an effect that occurs over a narrow range of concentrations and is associated with presynaptic activation of alpha7 nicotinic receptors.

    “Remarkably, at sub-nanomolar doses, the effect on LTP is reversed, and Aβ markedly enhances LTP. Discovered by Arancio and colleagues in a detailed analysis (Puzzo et al., 2008), enhancement occurs over a narrow range of concentrations and is associated with presynaptic activation of alpha7 nicotinic receptors.”

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  1. Dewachter I Ris L Croes S Borghgraef P Voets T Nilius B Godaux E Van Leuven F Differential affects of presenilin-1 deficiency and mutant presenilin-1 on synaptic activity Alzheimer's Association 10th International Conference on Alzheimer's Disease and Related Disorders 2006 S58 Madrid, Spain O53-03-08

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Authors
Puzzo, D., Privitera, L., Leznik, E., Fà, M., Staniszewski, A., Palmeri, A., & Arancio, O.
Affiliations
  • Columbia University Irving Medical Center (US)
  • University of Catania (IT)
  • Columbia University (US)
Corresponding author
Arancio, Ottavio
Venue
The Journal of Neuroscience
Published
2008-12-31
Volume
28
Issue
53
Pages
14537-14545
ISSN
  • 0270-6474 (ISSN-L)
  • 1529-2401
OpenAlex
W2078917784
Cited by
740
References
56
Citations by year
2026: 17 · 2025: 23 · 2024: 41 · 2023: 38 · 2022: 40 · 2021: 45 · 2020: 49 · 2019: 44 · 2018: 38 · 2017: 46 · 2016: 46 · 2015: 50 · 2014: 51 · 2013: 42 · 2012: 44
FWCI
28.04
Type
journal article
Language
en
Open access
Locations
  • Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • UNICA IRIS Institutional Research Information System (University of Cagliari) (submittedVersion)
Funders
  • Alzheimer's Association (NIRG-07-59597)
  • National Institutes of Health
  • National Institute of Neurological Disorders and Stroke (R01NS040045, R01NS049442, NS049442)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
Keywords
amyloid-beta, synaptic plasticity, long-term potentiation, hippocampus, memory, fear memory, contextual fear, alpha7 nicotinic acetylcholine receptor, Alzheimer's disease, amyloid-beta oligomers, neurotransmission
MeSH terms
Analysis of Variance, Animals, Bungarotoxins, Dose-Response Relationship, Drug, Electric Stimulation, Hippocampus, Humans, Male, Mecamylamine, Memory, Mice, Inbred C57BL, Neuronal Plasticity, Peptide Fragments, Receptors, Nicotinic, Synapses, 2-Amino-5-phosphonovalerate, Amyloid beta-Peptides, Mice, Knockout, Patch-Clamp Techniques, Excitatory Amino Acid Antagonists, Nicotinic Antagonists, Maze Learning, Excitatory Postsynaptic Potentials, Mice, alpha7 Nicotinic Acetylcholine Receptor, In Vitro Techniques

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