Spred1 is required for synaptic plasticity and hippocampus-dependent learning

Ellen Denayer, Tariq Ahmed, Hilde Brems, Geeske Van Woerden, Nils Zuiderveen Borgesius, Zsuzsanna Callaerts-Vegh, Akihiko Yoshimura, Dieter Hartmann, Ype Elgersma, Rudi D'Hooge, Eric Legius, Detlef Balschun

Research output: Contribution to journalArticle

64 Citations (Scopus)

Abstract

Germline mutations in SPRED1, a negative regulator of Ras, have been described in a neurofibromatosis type 1 (NF1)-like syndrome (NFLS) that included learning difficulties in some affected individuals. NFLS belongs to the group of phenotypically overlapping neurocardio-facial-cutaneous syndromes that are all caused by germ line mutations in genes of the Ras/mitogen-activated protein kinase extracellular signal-regulated kinase (ERK) pathway and that present with some degree of learning difficulties or mental retardation. We investigated hippocampus-dependent learning and memory as well as synaptic plasticity in Spred1-/- mice, an animal model of this newly discovered human syndrome. Spred1-/- mice show decreased learning and memory performance in the Morris water maze and visual-discrimination T-maze, but normal basic neuromotor and sensory abilities. Electrophysiological recordings on brain slices from these animals identified defects in short- and long-term synaptic hippocampal plasticity, including a disequilibrium between long-term potentiation (LTP) and long-term depression in CA1 region. Biochemical analysis, 4 h after LTP induction, demonstrated increased ERK-phosphorylation in Spred1-/- slices compared with those of wild-type littermates. This indicates that deficits in hippocampusdependent learning and synaptic plasticity induced by SPRED1 deficiency are related to hyperactivation of the Ras/ERK pathway.

Original languageEnglish
Pages (from-to)14443-14449
Number of pages7
JournalJournal of Neuroscience
Volume28
Issue number53
DOIs
Publication statusPublished - 31 Dec 2008
Externally publishedYes

Fingerprint

Neuronal Plasticity
Hippocampus
Learning
Extracellular Signal-Regulated MAP Kinases
Germ-Line Mutation
Long-Term Potentiation
Aptitude
ras Genes
Mitogen-Activated Protein Kinases
Intellectual Disability
Animal Models
Phosphorylation
Depression
Skin
Water
Brain

Keywords

  • Hippocampus
  • Learning
  • LTD
  • LTP
  • Morris water maze
  • Spred1
  • Synaptic plasticity

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Denayer, E., Ahmed, T., Brems, H., Van Woerden, G., Borgesius, N. Z., Callaerts-Vegh, Z., ... Balschun, D. (2008). Spred1 is required for synaptic plasticity and hippocampus-dependent learning. Journal of Neuroscience, 28(53), 14443-14449. https://doi.org/10.1523/JNEUROSCI.4698-08.2008

Spred1 is required for synaptic plasticity and hippocampus-dependent learning. / Denayer, Ellen; Ahmed, Tariq; Brems, Hilde; Van Woerden, Geeske; Borgesius, Nils Zuiderveen; Callaerts-Vegh, Zsuzsanna; Yoshimura, Akihiko; Hartmann, Dieter; Elgersma, Ype; D'Hooge, Rudi; Legius, Eric; Balschun, Detlef.

In: Journal of Neuroscience, Vol. 28, No. 53, 31.12.2008, p. 14443-14449.

Research output: Contribution to journalArticle

Denayer, E, Ahmed, T, Brems, H, Van Woerden, G, Borgesius, NZ, Callaerts-Vegh, Z, Yoshimura, A, Hartmann, D, Elgersma, Y, D'Hooge, R, Legius, E & Balschun, D 2008, 'Spred1 is required for synaptic plasticity and hippocampus-dependent learning', Journal of Neuroscience, vol. 28, no. 53, pp. 14443-14449. https://doi.org/10.1523/JNEUROSCI.4698-08.2008
Denayer E, Ahmed T, Brems H, Van Woerden G, Borgesius NZ, Callaerts-Vegh Z et al. Spred1 is required for synaptic plasticity and hippocampus-dependent learning. Journal of Neuroscience. 2008 Dec 31;28(53):14443-14449. https://doi.org/10.1523/JNEUROSCI.4698-08.2008
Denayer, Ellen ; Ahmed, Tariq ; Brems, Hilde ; Van Woerden, Geeske ; Borgesius, Nils Zuiderveen ; Callaerts-Vegh, Zsuzsanna ; Yoshimura, Akihiko ; Hartmann, Dieter ; Elgersma, Ype ; D'Hooge, Rudi ; Legius, Eric ; Balschun, Detlef. / Spred1 is required for synaptic plasticity and hippocampus-dependent learning. In: Journal of Neuroscience. 2008 ; Vol. 28, No. 53. pp. 14443-14449.
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