Localisation of ionotropic glutamate receptors in the central nervous system

Published on June 2, 2014   36 min

Other Talks in the Series: Synapses, Neurotransmitters and Receptor Channels

0:00
ELEK MOLNAR: Hello, my name is Elek Molnar. I'm Professor of Neuroscience at the School of Physiology and Pharmacology, University Bristol, in the United Kingdom. In this talk, I'm going to discuss different localization techniques for the investigation of ionotropic glutamate receptors in the central nervous system.
0:20
I will start with the introduction of the molecular organization and functional properties of glutamate receptors, then I will overview the main strategies you will use for the localization of endogenous glutamate receptors in the central nervous system. I will also discussed special challenges. Then, I will overview the various advantages and limitations of glutamate receptor localization strategies.
0:46
Glutamate is a single minus 8, which is responsible for most fast information transfer in the central nervous system. The excitatory neurotransmitter role of glutamate gradually emerged in the '50s and '60s. Early studies identified that glutamate was present in high concentration throughout the mammalian central nervous system. It Produced convulsions and excited single neurons. The development of increasingly specific pharmacological tools during the '70s started to reveal considerable functional diversity. The family of glutamate-activated cation channels, called ionotropic glutamate receptors, was classified into three major pharmacological families, defined by their most selective agonist, AMPA, Kainate, and NMDA. Radio ligands were produced, based on some of these subtype-specific agonists, which enabled the first ionotropic glutamate receptor localization studies, using gold radiography. In the mid '80s, a different type of glutamate receptor was identified. This glutamate receptor was directly couples to a second messenger system by GTP binding proteins and metabotropic glutamate receptors. However, ionotropic and metabotropic glutamate receptors remained elusive until the late '80s. The application of the newly emerging expression cloning approach led to a breakthrough, and provided original sequence information for the first ionotropic glutamate receptors, GluA1 and GluN1. Metabotrope Glutamate Receptor 1A, the first member of this family, was also discovered by expression cloning. Successive cloning by sequence homology led to the identification of additional ionotropic glutamate receptor subunits and various metabotropic glutamate receptor isoforms, plus various splice variants, were identified. The cloning of glutamate receptors provided a major stimulus for localization studies. In situ hybridization approach was used to map the expression profile of our messenger RNAs for various glutamate receptor subunits. The first antibodies for glutamate receptors started to appear in the early '90s. Subsequent immunolocalization studies started to reveal the subcellular distribution of various glutamate receptor proteins.
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Localisation of ionotropic glutamate receptors in the central nervous system

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