Subsynaptic segregation of metabotropic and ionotropic glutamate receptors as revealed by immunogold localization. 1994

Z Nusser, and E Mulvihill, and P Streit, and P Somogyi
Medical Research Council Anatomical Neuropharmacology Unit, University of Oxford, U.K.

Glutamate is a major neurotransmitter in the brain that acts both through fast ionotropic receptors and through slower metabotropic receptors coupled to G proteins. Both receptors are present throughout the somatodendritic domain of neurons as shown by immunohistochemical and patch clamp recording studies. Immunogold labelling revealed a concentration of metabotropic receptors at the edge, but not within the main body of anatomically defined synapses, raising the possibility that ionotropic and metabotropic receptors are segregated. We applied double immunogold labelling to study glutamatergic parallel and climbing fibre synapses in the cerebellar cortex. The ionotropic AMPA type receptors occupy the membrane opposite the release site in the main body of the synaptic junction, whereas the metabotropic receptors are located at the periphery of the same synapses. Furthermore, immunoreactivity for AMPA receptors is at least twice as high in the parallel fibre synapses as in glutamatergic mossy fibre synapses. We suggest that the spatial segregation of ionotropic and metabotropic glutamate receptors permits the differential activation of these receptors according to the amount of glutamate released presynaptically, whereas the different densities of the ionotropic receptor at distinct synapses could allow the same amount of glutamate to evoke fast responses of different magnitude.

UI MeSH Term Description Entries
D007150 Immunohistochemistry Histochemical localization of immunoreactive substances using labeled antibodies as reagents. Immunocytochemistry,Immunogold Techniques,Immunogold-Silver Techniques,Immunohistocytochemistry,Immunolabeling Techniques,Immunogold Technics,Immunogold-Silver Technics,Immunolabeling Technics,Immunogold Silver Technics,Immunogold Silver Techniques,Immunogold Technic,Immunogold Technique,Immunogold-Silver Technic,Immunogold-Silver Technique,Immunolabeling Technic,Immunolabeling Technique,Technic, Immunogold,Technic, Immunogold-Silver,Technic, Immunolabeling,Technics, Immunogold,Technics, Immunogold-Silver,Technics, Immunolabeling,Technique, Immunogold,Technique, Immunogold-Silver,Technique, Immunolabeling,Techniques, Immunogold,Techniques, Immunogold-Silver,Techniques, Immunolabeling
D008969 Molecular Sequence Data Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories. Sequence Data, Molecular,Molecular Sequencing Data,Data, Molecular Sequence,Data, Molecular Sequencing,Sequencing Data, Molecular
D002525 Cerebellar Cortex The superficial GRAY MATTER of the CEREBELLUM. It consists of two main layers, the stratum moleculare and the stratum granulosum. Cortex Cerebelli,Cerebelli, Cortex,Cerebellus, Cortex,Cortex Cerebellus,Cortex, Cerebellar
D000595 Amino Acid Sequence The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION. Protein Structure, Primary,Amino Acid Sequences,Sequence, Amino Acid,Sequences, Amino Acid,Primary Protein Structure,Primary Protein Structures,Protein Structures, Primary,Structure, Primary Protein,Structures, Primary Protein
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D013569 Synapses Specialized junctions at which a neuron communicates with a target cell. At classical synapses, a neuron's presynaptic terminal releases a chemical transmitter stored in synaptic vesicles which diffuses across a narrow synaptic cleft and activates receptors on the postsynaptic membrane of the target cell. The target may be a dendrite, cell body, or axon of another neuron, or a specialized region of a muscle or secretory cell. Neurons may also communicate via direct electrical coupling with ELECTRICAL SYNAPSES. Several other non-synaptic chemical or electric signal transmitting processes occur via extracellular mediated interactions. Synapse
D017470 Receptors, Glutamate Cell-surface proteins that bind glutamate and trigger changes which influence the behavior of cells. Glutamate receptors include ionotropic receptors (AMPA, kainate, and N-methyl-D-aspartate receptors), which directly control ion channels, and metabotropic receptors which act through second messenger systems. Glutamate receptors are the most common mediators of fast excitatory synaptic transmission in the central nervous system. They have also been implicated in the mechanisms of memory and of many diseases. Excitatory Amino Acid Receptors,Glutamate Receptors,Receptors, Excitatory Amino Acid,Excitatory Amino Acid Receptor,Glutamate Receptor,Receptor, Glutamate
D051381 Rats The common name for the genus Rattus. Rattus,Rats, Laboratory,Rats, Norway,Rattus norvegicus,Laboratory Rat,Laboratory Rats,Norway Rat,Norway Rats,Rat,Rat, Laboratory,Rat, Norway,norvegicus, Rattus
D018091 Receptors, AMPA A class of ionotropic glutamate receptors characterized by their affinity for the agonist AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid). AMPA Receptors,Quisqualate Receptors,AMPA Receptor,Quisqualate Receptor,Receptor, AMPA,Receptor, Quisqualate,Receptors, Quisqualate
D018094 Receptors, Metabotropic Glutamate Cell surface proteins that bind glutamate and act through G-proteins to influence second messenger systems. Several types of metabotropic glutamate receptors have been cloned. They differ in pharmacology, distribution, and mechanisms of action. Glutamate Receptors, Metabotropic,Metabotropic Glutamate Receptors,Receptors, Glutamate, Metabotropic,Metabotropic Glutamate Receptor,Glutamate Receptor, Metabotropic,Receptor, Metabotropic Glutamate

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