Title: Poster session: Spred1 is required for synaptic plasticity and hippocampus-dependent learning
Authors: Ahmed, Tariq
Denayer, E.
Yoshimura, A.
Balschun, Detlef
D'Hooge, Rudi #
Issue Date: Jul-2008
Host Document: FENS abstract vol:4
Conference: FENS forum of European Neuroscience edition:6 location:Geneva, Switserland date:12-16 July 2008
Article number: 219.1
Abstract: Spred proteins belong to a novel family of evolutionary conserved, negative regulators of the Ras/mitogen-activated protein kinase (MAPK) signal transduction pathway. Germline mutations in SPRED1 were recently shown to cause a neurofibromatosis type 1 (NF1) -like syndrome in children that included learning difficulties, suggesting SPRED1 to be involved in neural and behavioural plasticity. We investigated hippocampus-dependent learning and memory as well as synaptic plasticity in Spred1 knock-out mice, an animal model of this newly discovered human syndrome.
Spred1 knockout mice showed decreased performance in the hidden version of the Morris water maze, but normal basic neuromotor and sensory abilities. When examined for synaptic plasticity in the hippocampal CA1 region in vitro, Spred1 knockout mice displayed decremental long-term potentiation (LTP) after a single theta-burst stimulation (TBS) returning to baseline values after 55 min. LTP in WT littermates, however, was robust and maintained for at least 4 h. In contrast, LTD induced by a long-train of low-frequency stimulation (2 Hz, 15 min) was very robust in Spred1 knockout mice but only transient in WT mice. The observed imbalance between LTP and LTD in Spred1 knockout mice is likely to be caused by a “pathophysiological” hyperactivation of the Ras-MAPK pathway. Thus, delineating this pathway in cognition and synaptic plasticity may open up new therapeutic approaches for NF1-like human disorders.
Publication status: published
KU Leuven publication type: IMa
Appears in Collections:Laboratory for Biological Psychology
# (joint) last author

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