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The δ2 glutamate receptor: a key molecule controlling synaptic plasticity and structure in Purkinje cells

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Abstract

The orphan glutamate receptor δ2 (GluRδ2) is predominantly expressed in cerebellar Purkinje cells and plays a crucial role in cerebellar functions; mice that lack the GluRδ2 gene display ataxia and impaired motor-related learning tasks. However, when expressed alone or with other glutamate receptors, GluRδ2 does not form functional glutamate-gated ion channels nor does it bind to glutamate analogs. Therefore, the mechanisms by which GluRδ2 participates in cerebellar functions have been elusive. Studies of mutant mice, such as lurcher, hotfoot, and GluRδ2 knockout mice, have provided clues to the structure and function of GluRδ2. Particularly, morphological and electrophysiological analyses of hotfoot and GluRδ2 knockout mice have indicated a unique role of GluRδ2 in aligning and maintaining the postsynaptic element with the presynaptic one at parallel fiber (PF)-Purkinje cell synapses. In addition, GluRδ2 was expressed in newly formed ectopic PF-Purkinje cell synapses found after blockade of electrical activity in adult cerebellum. Moreover, application of an antibody specific for GluRδ2’s extracellular N-terminal region abrogated synaptic plasticity. These results indicate that GluRδ2 plays a direct role in synapse formation and synaptic plasticity in adult mice. Based on these results, two hypotheses about mechanisms by which GluRδ2 functions are proposed in this article.

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Correspondence to Michisuke Yuzaki.

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Yuzaki, M. The δ2 glutamate receptor: a key molecule controlling synaptic plasticity and structure in Purkinje cells. The Cerebellum 3, 89–93 (2004). https://doi.org/10.1080/14734220410028921

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