Cited by 174Down syndrome and intellectual disability researchNeuroscience and Neuropharmacology ResearchMemory and Neural Mechanisms

Deficits in hippocampal CA1 LTP induced by TBS but not HFS in the Ts65Dn mouse: a model of down syndrome.

Costa, Alberto C.S., Grybko, Michael J.·2005·Neuroscience Letters

Abstract

Down syndrome (DS) is the most common genetically defined cause of intellectual disabilities. Both hippocampal function and volume seem to be disproportionally reduced in individuals with DS and in at least one aneuploid murine model of DS, the Ts65Dn mouse. Two previous studies by one research group have reported deficits in long-term potentiation (LTP) induced by in vitro high-frequency stimulation (HFS) of hippocampal CA1 synapses of adult Ts65Dn mice. Here, we report on the results of our own investigation on LTP in Ts65Dn mice. This study was designed to confirm the previous findings and possibly shed some light onto potential mechanisms underlying the reported deficit in this important form of long-term synaptic plasticity in a mouse model of DS. LTP was induced in area CA1 with either theta burst stimulation (TBS) or HFS. Contrary to the previous reports, our results showed no significant difference in HFS-induced LTP between Ts65Dn and euploid littermate mice. We have found, however, a significant reduction of the amount of TBS-induced LTP in Ts65Dn mice compared to euploid controls. Because this specific LTP deficit can be rescued by bath application of picrotoxin (10 microM), we hypothesize that an increase in GABA(A)-mediated inhibition or in plasticity of the inhibitory circuitry in Ts65Dn mice may underlie the observed deficits. However, future experiments to examine the state of hippocampus CA1 GABAergic inhibition in Ts65Dn mice will be necessary to further exp…

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Crossref · 10.1016/j.neulet.2005.03.031

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  • In Ts65Dn hippocampus, long-term potentiation (LTP) induction fails due to excessive GABA-mediated inhibition.

    “A seminal study in the field found failure of induction of long-term potentiation (LTP) in the Ts65Dn hippocampus due to excessive GABA-mediated inhibition and a wide array of following studies have confirmed this finding (Siarey et al., 1997, 1999; Kleschevnikov et al., 2004; Costa and Grybko, 2005; Fernandez et al., 2007).”

    From Neurodevelopment in Down syndrome: Concordance in humans and models (2022) · cites this paper as Costa and Grybko, 2005

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Authors
Costa, A. C. S., & Grybko, M. J.
Affiliations
University of Denver (US)
Corresponding author
Costa, Alberto C.S.
Venue
Neuroscience Letters
Publisher
Elsevier BV
Published
2005-07
Volume
382
Issue
3
Pages
317-322
ISSN
0304-3940 (ISSN-L)
OpenAlex
W2082869264
Cited by
174
References
25
Citations by year
2026: 2 · 2025: 8 · 2024: 3 · 2023: 3 · 2022: 5 · 2021: 13 · 2020: 7 · 2019: 11 · 2018: 8 · 2017: 9 · 2016: 6 · 2015: 7 · 2014: 7 · 2013: 12 · 2012: 14
FWCI
7.69
Type
journal article
Language
en
Open access
closed
Locations
  • Neuroscience Letters (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD037424, R01HD037113, HD-24605, HD37424, P01HD024605, HD37113)
Topics
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Down syndrome and intellectual disability research
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
Keywords
Down syndrome, Ts65Dn mouse model, hippocampal CA1, long-term potentiation, theta burst stimulation, high-frequency stimulation, picrotoxin, GABAA inhibition, synaptic plasticity, intellectual disability, aneuploidy
MeSH terms
Animals, Disease Models, Animal, Down Syndrome, Electric Stimulation, Hippocampus, Male, Synaptic Transmission, Organ Culture Techniques, Picrotoxin, Long-Term Potentiation, GABA Antagonists, Excitatory Postsynaptic Potentials, Mice

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