Glutamate receptor function

Development of glutamate receptor function in immature synapses and x-linked mental retardation

PhD student: Vacancy, for further information please send an e-mail to: maaike.leusden@neurosciencecampus-amsterdam.nl

Home Institute: Neuroscience Campus Amsterdam; Principle Investigator; Huibert Mansvelder and Rhiannon Meredith,
Host Institute: Bordeaux Neurosciences Institute; Principle Investigator: Daniel Choquet

Executive Summary
Early development of excitatory synapses requires expression of glutamate receptors for both synapse formation and plasticity. Excitatory ionotropic (iGluRs) and metabotropic glutamate receptors (mGluRs) are expressed prenatally and are important for neuronal migration, synaptic circuit formation and plasticity during brain development. IGluRs are highly mobile during different stages of synaptic development, and receptor motility is linked to synaptic plasticity. In mental retardation, which affects 2-3% of the worldwide population, neuronal and synaptic development is compromised and changes in glutamatergic plasticity and receptor signalling occur. A unifying pathological feature across many forms of mental retardation is the abnormal shape of synaptic spines. Early stages of the formation of glutamatergic synapses and signalling mechanisms prior to abnormal spine pathology are poorly understood.

The main aim of the project is to investigate the functional development of glutamate receptors at single synapses and synaptic networks during early brain development and in mental retardation, and to study by what mechanisms mGluR activation affects glutamate receptor mobility and spine stabilization at single synapses.

We will take a multi-disciplinary approach using electrophysiology, imaging and pharmacological intervention to focus directly on dendritic spines at individual synapses. Experiments will be carried out in neuronal cultures made from hippocampus and prefrontal cortical networks of transgenic and wild type mice. Synaptic and extra synaptic mobility of iGluRs and mGluRs will be tracked using PALM microscopy on different types of spines.