Cited by 84Alzheimer's disease research and treatmentsNeuroscience and Neuropharmacology ResearchMemory and Neural Mechanisms

Dopaminergic neurotransmission dysfunction induced by amyloid-β transforms cortical long-term potentiation into long-term depression and produces memory impairment

Moreno-Castilla, Perla, Rodriguez-Duran, Luis F., Guzman-Ramos, Kioko, Barcenas-Femat, Alejandro, Escobar, Martha L., Bermudez-Rattoni, Federico·2016·Neurobiology of Aging

Abstract

Alzheimer's disease (AD) is a neurodegenerative condition manifested by synaptic dysfunction and memory loss, but the mechanisms underlying synaptic failure are not entirely understood. Although dopamine is a key modulator of synaptic plasticity, dopaminergic neurotransmission dysfunction in AD has mostly been associated to noncognitive symptoms. Thus, we aimed to study the relationship between dopaminergic neurotransmission and synaptic plasticity in AD models. We used a transgenic model of AD (triple-transgenic mouse model of AD) and the administration of exogenous amyloid-β (Aβ) oligomers into wild type mice. We found that Aβ decreased cortical dopamine levels and converted in vivo long-term potentiation (LTP) into long-term depression (LTD) after high-frequency stimulation delivered at basolateral amygdaloid nucleus-insular cortex projection, which led to impaired recognition memory. Remarkably, increasing cortical dopamine and norepinephrine levels rescued both high-frequency stimulation -induced LTP and memory, whereas depletion of catecholaminergic levels mimicked the Aβ-induced shift from LTP to LTD. Our results suggest that Aβ-induced dopamine depletion is a core mechanism underlying the early synaptopathy and memory alterations observed in AD models and acts by modifying the threshold for the induction of cortical LTP and/or LTD.

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Crossref · 10.1016/j.neurobiolaging.2016.02.021

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Authors
Moreno-Castilla, P., Rodriguez-Duran, L. F., Guzman-Ramos, K., Barcenas-Femat, A., Escobar, M. L., & Bermudez-Rattoni, F.
Affiliations
Universidad Nacional Autónoma de México (MX)
Venue
Neurobiology of Aging
Publisher
Elsevier BV
Published
2016-05
Volume
41
Pages
187-199
ISSN
0197-4580 (ISSN-L)
OpenAlex
W2288964146
Cited by
84
References
69
Citations by year
2026: 5 · 2025: 11 · 2024: 7 · 2023: 8 · 2022: 10 · 2021: 11 · 2020: 8 · 2019: 6 · 2018: 9 · 2017: 8 · 2016: 1
FWCI
6.45
Type
journal article
Language
en
Open access
closed
Locations
  • Neurobiology of Aging (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • CONACYT (155242 and CB 250870)
  • PAPIIT-UNAM (IN209413, IN208616, IN215816)
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
Alzheimer's disease, amyloid-beta oligomers, dopamine signaling, dopamine depletion, long-term potentiation, long-term depression, synaptic plasticity, recognition memory impairment, norepinephrine, synaptopathy, triple transgenic mouse model
MeSH terms
Alzheimer Disease, Animals, Cerebral Cortex, Disease Models, Animal, Dopamine, Male, Memory Disorders, Mice, Transgenic, Synaptic Transmission, Neuronal Plasticity, Amyloid beta-Peptides, Long-Term Potentiation, Long-Term Synaptic Depression, Mice, Dopaminergic Neurons

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