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Title: Spred1 is required for synaptic plasticity and hippocampus-dependent learning
Authors: Denayer, Ellen
Ahmed, Tariq
Brems, Hilde
Van Woerden, Geeske
Zuiderveen-Borgesius, Nils
Callaerts-Vegh, Zsuzsanna
Yoshimura, Akihiko
Hartmann, Dieter
Elgersma, Ype
D'Hooge, Rudi
Legius, Eric ×
Balschun, Detlef #
Issue Date: Dec-2008
Publisher: The Society for Neuroscience
Series Title: Journal of Neuroscience vol:28 issue:53 pages:14443-14449
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 hippocampus-dependent learning and synaptic plasticity induced by SPRED1 deficiency are related to hyperactivation of the Ras/ERK pathway.
ISSN: 0270-6474
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory for Biological Psychology
Department of Human Genetics - miscellaneous
Molecular Genetics Section (-)
Clinical Genetics Section (-)
Laboratory for Neurofibromatosis Research
× corresponding author
# (joint) last author

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