mGluR in DUM neuronen of Locusta migratoria.

By Daniel Janssen 

Most of the excitatory synapses in the central nervous system (CNS) use glutamate as a chemical messenger. The activity of the glutamate receptor (GluR) plays a key role in the modulation of a number of neuronal channels including voltage-sensitive Ca2+ and K+ channels, G protein-regulated inward rectifier K+ channels, GABA receptors and ionotropic receptors (iGluR). The focus of this study will be the metabotropic glutamate receptors (mGluR). The mGluR can be classified into three groups based on their sequence homology, transduction mechanisme and pharmacology. Group I stimulate phospholipase C, resulting in a Ca2+ release from internal stores. Group II and III are negatively coupled to adenylyl cyclase via pertussis toxin-sensitive G proteins. The modulatory effects of the ligand-receptor binding can either be potentiation or inhibition of Glu-mediated transmission, and the consequence can be as diverse as neuronal death, neuronal development, control of movements and olfactory memory. The discovery of this multiplicity of mGluR and their crucial role in the modulation of neurotransmission, appears therefore as a great hope in the development of new drugs able to control excitatory transmission in the CNS. 

In this specific study, mGluR in median unpaired dorsal (DUM) neurons, isolated out of the Locusta migratoria will be characterized and identified by means of immunohistochemical and molecular techniques (RT-PCR). Their electrophysical properties will be studied with the help of the Patch Clamp technique in “whole cell’ configuration. The effects of glutamate on different ionchannels will be investigated, also other specific agonists, antagonist and invertebrate toxins will be tested. These effects will be described in a attempt to define the exact transduction mechanisms, functional and physiological roles of mGluR in DUM neurones. It will become apparent that mGluR are the excellent targests for the testing and development of drugs that modulate excitatory synaptic transmission. Such drugs could be useful in treating numerous diseases involving deregulation of Glu transmission and also in agriculture, mGluR specific drugs can be used as pesticides.

 Isolated efferente DUM neurons (A&B) of the metathoracic ganglion of Locusta migratoria (C).   

  A glas-pipette is sealed on the cell surface (A&B) and suction was applied in the pipette to obtain the whole cell configuration (C&D)