PT  - JOURNAL ARTICLE
AU  - Wataru Kakegawa
AU  - Taisuke Miyazaki
AU  - Kazuhisa Kohda
AU  - Keiko Matsuda
AU  - Kyoichi Emi
AU  - Junko Motohashi
AU  - Masahiko Watanabe
AU  - Michisuke Yuzaki
TI  - The N-Terminal Domain of GluD2 (GluRδ2) Recruits Presynaptic Terminals and Regulates Synaptogenesis in the Cerebellum <em>In Vivo</em>
AID  - 10.1523/JNEUROSCI.6013-08.2009
DP  - 2009 May 06
TA  - The Journal of Neuroscience
PG  - 5738--5748
VI  - 29
IP  - 18
4099  - http://www.jneurosci.org/content/29/18/5738.short
4100  - http://www.jneurosci.org/content/29/18/5738.full
SO  - J. Neurosci.2009 May 06; 29
AB  - The δ2 glutamate receptor (GluRδ2; GluD2), which is predominantly expressed on postsynaptic sites at parallel fiber (PF)–Purkinje cell synapses in the cerebellum, plays two crucial roles in the cerebellum: the formation of PF synapses and the regulation of long-term depression (LTD), a form of synaptic plasticity underlying motor learning. Although the induction of LTD and motor learning absolutely require signaling via the cytoplasmic C-terminal domain of GluD2, the mechanisms by which GluD2 regulates PF synaptogenesis have remained unclear. Here, we examined the role of the extracellular N-terminal domain (NTD) of GluD2 on PF synaptogenesis by injecting Sindbis virus carrying wild-type (GluD2wt) or mutant GluD2 into the subarachnoid supracerebellar space of GluD2-null mice. Remarkably, the expression of GluD2wt, but not of a mutant GluD2 lacking the NTD (GluD2ΔNTD), rapidly induced PF synapse formation and rescued gross motor dyscoordination in adult GluD2-null mice just 1 d after injection. In addition, although the kainate receptor GluR6 (GluK2) did not induce PF synaptogenesis, a chimeric GluK2 that contained the NTD of GluD2 (GluD2NTD–GluK2) did. Similarly, GluD2wt and GluD2NTD–GluK2, but not GluD2ΔNTD, induced synaptogenesis in heterologous cells in vitro. In contrast, LTD was restored in GluD2-null Purkinje cells expressing a mutant GluD2 lacking the NTD. These results indicate that the NTD of GluD2 is necessary and sufficient for the function of GluD2 in the regulation of PF–Purkinje cell synaptogenesis. Furthermore, our results suggest that GluD2 differently regulates PF synaptogenesis and cerebellar LTD through the extracellular NTD and the cytoplasmic C-terminal end, respectively.