title: Delta-glutamate receptors are differentially distributed at parallel and climbing fiber synapses on Purkinje cells.
abstract: Neurons containing multiple excitatory inputs may sort and target glutamate receptor subtypes to subsets of synapses. A good model for testing this hypothesis is the Purkinje cell, which expresses significant levels of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate, kainate, N-methyl-D-aspartate, delta-, and metabotropic glutamate receptors. Purkinje cells receive two excitatory inputs, the parallel and climbing fibers; the combined effect of stimulation of these two inputs is to produce long-term depression of parallel fiber/Purkinje cell neurotransmission. Distribution of glutamate receptors in these two synapse populations in rat cerebella was studied using preembedding immunocytochemistry with antibodies to GluR1, GluR2/3, GluR5-7, NR1, delta 1/2, and mGluR1 alpha. Moderate/dense postsynaptic staining was most frequent in postsynaptic densities and spines of both parallel and climbing fiber synapses with mGluR1 alpha antibody, was intermediate in frequency with GluR2/3 and GluR5-7 antibodies, and was least frequent with GluR1 and NR1 antibodies. The most striking finding was the absence of significant postsynaptic staining with delta 1/2 antibody in climbing fiber synapses in adult animals, even though postsynaptic staining was prevalent in parallel fiber synapses with this antibody. In contrast to adults, moderate/dense postsynaptic immunolabeling of climbing fiber synapses with delta 1/2 antibody was common in rats at 10 days postnatal. This study provides direct morphological evidence that delta-glutamate receptors are differentially targeted to synapse populations. Our results support previous suggestions that delta 2 is involved in development of parallel and climbing fiber synapses and in long-term depression of parallel fiber/Purkinje synaptic responses in adults.
authors.affiliation: Laboratory of Neurochemistry, NIDCD, NIH, Bethesda, MD 20892-4162, USA.
authors.forename: H M
authors.initials: HM
authors.lastname: Zhao
authors.forename: R J
authors.initials: RJ
authors.lastname: Wenthold
authors.forename: Y X
authors.initials: YX
authors.lastname: Wang
authors.forename: R S
authors.initials: RS
authors.lastname: Petralia
mesh_terms: D000375:Aging / Q000378:metabolism; D000818:Animals; D007150:Immunohistochemistry; D007536:Isomerism; D008854:Microscopy, Electron; D009412:Nerve Fibers / Q000378:metabolism / Q000648:ultrastructure; D011689:Purkinje Cells / Q000378:metabolism* / Q000648:ultrastructure; D051381:Rats; D018091:Receptors, AMPA / Q000378:metabolism; D017470:Receptors, Glutamate / Q000378:metabolism*; D018092:Kainic Acid Receptors / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D013569:Synapses / Q000378:metabolism* / Q000648:ultrastructure; D014018:Tissue Distribution
chemical_list: D018091:Receptors, AMPA; D017470:Receptors, Glutamate; D018092:Kainic Acid Receptors; D016194:Receptors, N-Methyl-D-Aspartate