SUBSYNAPTIC SEGREGATION OF METABOTROPIC AND IONOTROPIC GLUTAMATE RECEPTORS AS REVEALED BY IMMUNOGOLD LOCALIZATION

Glutamate is a major neurotransmitter in the brain that acts both thro ugh fast ionotropic receptors and through slower metabotropic receptor s coupled to G proteins, Both receptors are present throughout the som atodendritic domain of neurons as shown by immunohistochemical(5,6,19, 20,24) and patch clamp recording studies.(8,9,16,28,37) Immunogold lab elling revealed a concentration of metabotropic receptors at the edge, but not within the main body of;anatomically defined synapses,(6) rai sing the possibility that ionotropic and metabotropic receptors are se gregated. We applied double immunogold labelling to study glutamatergi c parallel and climbing fibre synapses in the cerebellar cortex, The i onotropic AMPA type receptors occupy the membrane opposite the release site in the main body of the synaptic junction, whereas the metabotro pic receptors are located at the periphery of the same synapses. Furth ermore, immunoreactivity for AMPA receptors is at least twice as high in the parallel fibre synapses as in glutamatergic messy fibre synapse s. We suggest that the spatial segregation of ionotropic and metabotro pic glutamate receptors permits the differential activation of these r eceptors according to the amount of glutamate released presynaptically , whereas the different densities of the ionotropic receptor at distin ct synapses could allow the same amount of glutamate to evoke fast res ponses of different magnitude.