NMDA receptor subunits GluR epsilon 1, GluR epsilon 3 and GluR zeta 1 are enriched at the mossy fibre-granule cell synapse in the adult mouse cerebellum

Citation
K. Yamada et al., NMDA receptor subunits GluR epsilon 1, GluR epsilon 3 and GluR zeta 1 are enriched at the mossy fibre-granule cell synapse in the adult mouse cerebellum, EUR J NEURO, 13(11), 2001, pp. 2025-2036
Citations number
80
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Neurosciences & Behavoir
Journal title
EUROPEAN JOURNAL OF NEUROSCIENCE
ISSN journal
0953-816X → ACNP
Volume
13
Issue
11
Year of publication
2001
Pages
2025 - 2036
Database
ISI
SICI code
0953-816X(200106)13:11<2025:NRSGE1>2.0.ZU;2-W
Abstract
Cerebellar N-methyl-D-aspartate (NMDA) receptors are concentrated in the gr anular layer and are involved in motor coordination and the induction of lo ng-term potentiation at mossy fibre-granule cell synapses. In the present s tudy, we used immunohistochemistry to examine the distribution of NMDA rece ptor subunits in the adult mouse cerebellum. We found that appropriate peps in pretreatment of sections greatly enhanced the sensitivity and specificit y of immunohistochemical detection. As a result, intense immunolabelling fo r GluR epsilon1 (NR2A), GluR epsilon3 (NR2C), and GluR zeta1 (NR1) all appe ared in synaptic glomeruli of the granular layer. Double immunofluorescence showed that these subunits were colocalized in individual synaptic glomeru li. Within the glomerulus, NMDA receptor subunits were located between cent rally-located huge mossy fibre terminals and peripherally-located tiny Golg i axon terminals. By immunoelectron microscopy, all three subunits were det ected at the postsynaptic junction in granule cell dendrites, forming synap ses with mossy fibre terminals. Consistent with the known functional locali zation, GluR epsilon1, GluR epsilon3, and GluR zeta1 are, thus, anatomicall y concentrated at the mossy fibre-granule cell synapse. By contrast, immuno histochemical signals were very low in Purkinje cell somata and dendrites i n the molecular layer. The lack of GluR zeta1 immunolabelling in Purkinje c ells was unexpected because the cells express GluR zeta1 mRNA at high level s and high levels of GluR zeta1 protein in the molecular layer were reveale d by immunoblot. As Purkinje cells are exceptionally lacking GluR epsilon e xpression, the discrepant result may provide in vivo evidence suggesting th e importance of accompanying GluR epsilon subunits in synaptic localization of GluR zeta1.