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Molecular and cellular mechanisms underlying learning and mental retardation disorders

Principal investigator: Prof. dr. Ype Elgersma

Our lab seeks to get insight in the molecular and cellular basis of learning and memory formation. Central to our approach is the use of genetically engineered mice as a tool to dissect these mechanisms. We are particularly interested in hippocampal plasticity and hippocampus dependent learning. Mutation-induced changes that occur in this brain region are analyzed at the biochemical, cellular and behavioral level. By analyzing the mutant mice at all these levels we hope to understand the specific function of these genes and proteins in synaptic plasticity, and to get insight in the molecular mechanisms underlying learning and memory. This knowledge is essential to develop treatments for patients with (genetic) diseases that affect normal brain function. To translate our findings to the patients, we are closely collaborating with the Sophia Children’s Hospital (the CoRe (Cognitive Research) team). The genes and proteins that we focus on are CaMKII, Ube3a and proteins belonging to the RAS-ERK-MTOR signaling pathway. The associated diseases are Angelman Syndrome, Neurofibromatosis (NF1), Noonan syndrome, Costello syndrome, Cowden disease and Tuberous Sclerosis (TSC).

Selected publications

  • Van Woerden et al. Beta-CaMKII controls the direction of plasticity at parallel-Purkinje cell synapses. Nature Neurosci, 2009, 12, 823-825 (pubmed)
  • Krab et al. Effect of simvastatin on cognitive functioning in children with Neurofibromatosis type 1: a randomized controlled trial. JAMA 2008, 300:287-294 (pubmed)
  • Goorden et al. Cognitive deficits in Tsc1 mice in the absence of cerebral lesions and seizures. Ann Neurol 2007, 62, 648-655 (pubmed)
  • Hojjati et al. Kinase activity is not required for alphaCaMK2-dependent presynaptic plasticity at hippocampal CA3-CA1 synapses. Nature Neurosci. 2007, 10, 1125-1127 (pubmed)
  • Van Woerden et al. Rescue of neurological deficits in a mouse model for Angelman syndrome by reduction of alphaCaMKII inhibitory phosphorylation. Nature Neurosci 2007, 10, 280-282.(pubmed)
  • Hansel et al. AlphaCaMK2 Is essential for Cerebellar LTD and motor learning. Neuron 2006, 51, 835-843 (pubmed)
  • Elgersma et al. Mouse genetic approaches to investigating calcium/calmodulin-dependent protein kinase II function in plasticity and cognition. J Neurosci 2004, 24:8410-8415. (pubmed)
  • Elgersma et al. Inhibitory autophosphorylation of CaMKII controls PSD association, plasticity, and learning. Neuron 2002, 36:493-505 (pubmed)

Vacancies

  • Postdoc position available to study the molecular and cellular mechanisms underlying hippocampal learning and mental retardation. Applicants are expected to have extensive experience in molecular biology and/or stem cell research.
  • Postdoc position available to study the molecular and cellular mechanisms underlying hippocampal learning and mental retardation. Applicants are expected to have extensive experience in whole-cell electrophysiology.
  • PhD position available to study the molecular and cellular mechanisms underlying hippocampal learning and mental retardation.