Differential plasma membrane distribution of metabotropic glutamate receptors mGluR1α, mGluR2 and mGluR5, relative to neurotransmitter release sites Journal Article

Author(s): Luján, Rafael; Roberts, John D; Shigemoto, Ryuichi; Ohishi, Hitoshi; Somogyi, Péter
Article Title: Differential plasma membrane distribution of metabotropic glutamate receptors mGluR1α, mGluR2 and mGluR5, relative to neurotransmitter release sites
Abstract: Two group I metabotropic glutamate receptor subtypes, mGluR1 and mGluR5, have been reported to occur in highest concentration in an annulus surrounding the edge of the postsynaptic membrane specialisation. In order to determine whether such a distribution is uniform amongst postsynaptic mGluRs, their distribution was compared quantitatively by a pre-embedding silver-intensified immunogold technique at electron microscopic level in hippocampal pyramidal cells (mGluR5), cerebellar Purkinje cells (mGluR1α) and Golgi cells (mGluR2). The results show that mGluR1α, mGluR5 and mGluR2 each have a distinct distribution in relation to the glutamatergic synaptic junctions. On dendritic spines, mGluRlα and mGluR5 showed the highest receptor density in a perisynaptic annulus (defined as within 60 nm of the edge of the synapse) followed by a decreasing extrasynaptic (60-900 nm) receptor level, but the gradient of decrease and the proportion of the perisynaptic pool (mGluR1α, ~ 50%; vs mGluR5, ~ 25%) were different for the two receptors. The distributions of mGluRlα and mGluR5 also differed significantly from simulated random distributions. In contrast, mGluR2 was not closely associated with glutamatergic synapses in the dendritic plasma membrane of cerebellar Golgi cells and its distribution relative to synapses is not different from simulated random distribution in the membrane. The somatic membrane, the axon and the synaptic boutons of the GABAergic Golgi cells also contained immunoreactive mGluR2 that is not associated with synaptic specialisations. In the hippocampal CA1 area the distribution of immunoparticles for mGluR5 on individual spines was established using serial sections. The results indicate that dendritic spines of pyramidal cells are heterogeneous with respect to the ratio of perisynaptic to extrasynaptic mGluR5 pools and about half of the immunopositive spines lack the perisynaptic pool. The quantitative comparison of receptor distributions demonstrates that mGluRlα and mGluR5, but not mGluR2, are highly compartmentalised in different plasma membrane domains. The unique distribution of each mGluR subtype may reflect requirements for different transduction and effector mechanisms between cell types and different domains of the same cell, and suggests that the precise placement of receptors is a crucial factor contributing to neuronal communication.
Keywords: Cerebellum; Hippocampus; Immunocytochemistry; Glutamate; Quantitative immunogold; Synaptic junction
Journal Title: Journal of Chemical Neuroanatomy
Volume: 13
Issue 4
ISSN: 0891-0618
Publisher: Elsevier  
Date Published: 1997-10-04
Start Page: 219
End Page: 241
DOI: 10.1016/S0891-0618(97)00051-3
Open access: no