Understanding activation of AMPA neuroreceptors in health and neurodevelopmental disorders

Ionotropic glutamate receptors are transmembrane proteins ubiquitous in the vertebrate brain. They are subdivided into four families: NMDA, AMPA, kainate and delta receptors. Together, these neuroreceptors mediate communication between neurons at excitatory synapses, with each of them performing a specialized role. AMPA receptors (AMPARs), the focus of this project, ensure the speed of synaptic transmission: they are the first ones to bind neurotransmitter glutamate released from the presynaptic neuron. Whenever AMPARs bind glutamate, they open their integral ion channels allowing influx of Na+ ions and depolarizing the synaptic membrane. Several mutations of AMPARs have been implicated in various neurological diseases, such as autism, schizophrenia, epilepsy and neurodevelopmental disorders. One mutation, Lurcher, has profound effects on the activity of AMPARs and the main aim of this project is to use the mutant to answer the question whether all subunits contribute equally to the activation of the receptor. In the next stage, I will examine whether the anti-epileptic drug Perampanel affects the Lurcher mutant.