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Differential Distribution of Metabotropic Glutamate Receptors in the Cerebellum
Laboratory for Neuronal Circuit Dynamics |
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In the cerebellar cortex, the release of the neurotransmitter glutamate from parallel fiber terminals activates glutamate receptors at their synapses with dendritic spines of Purkinje cells. These glutamate receptors involve ionotropic receptors, which form ligand-gated ion channels, as well as metabotropic receptors, which are coupled to G-proteins that modulate intracellular second messenger systems.
Immunogold techniques make it possible to investigate the subcellular and subsynaptic distribution of glutamate receptors. In general, ionotropic glutamate receptors have a preferential postsynaptic localization, while metabotropic glutamate receptors (mGluRs) are postsynaptic, presynaptic or both depending on the receptor subtype and the system studied.
Pre-embedding immunogold methods for electron microscopy were used in a collaboration between the Laboratory for Neuronal Circuit Dynamics and Prof. Pedro Grandes at the Basque Country University, Bilbao, Spain, to study the distribution of the group I mGluR1b and the group III mGluR4a in the cerebellar molecular layer. The parallel fiber-Purkinje cell synapse exhibited presynaptic clusters of mGluR4a interspaced by a constant distance of 60nm. The mGluR1b is distributed perisynaptically (25% of gold particles) and extrasynaptically (10-18% of immunoparticles) to postsynaptic densities of dendritic spines. This highly specific arrangement of mGluR1b and mGluR4a suggests an important role for these receptors in the modulation of synaptic transmission at parallel fiber-Purkinje cell synapses.
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Schematic drawing of a parallel fiber-Purkinje cell synapse with presynaptic clusters of mGluR4a (red, A) interspaced by a constant distance of 60nm. The mGluR1b (green, B) is distributed perisynaptically and extrasynaptically to postsynaptic densities of dendritic spines.
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