Distinct synaptic and extrasynaptic NMDA receptors in developing cerebellar granule neurons

Citation
G. Rumbaugh et S. Vicini, Distinct synaptic and extrasynaptic NMDA receptors in developing cerebellar granule neurons, J NEUROSC, 19(24), 1999, pp. 10603-10610
Citations number
30
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Neurosciences & Behavoir
Journal title
JOURNAL OF NEUROSCIENCE
ISSN journal
0270-6474 → ACNP
Volume
19
Issue
24
Year of publication
1999
Pages
10603 - 10610
Database
ISI
SICI code
0270-6474(199912)19:24<10603:DSAENR>2.0.ZU;2-L
Abstract
In rat cerebellar granule neurons, mRNA and protein levels of the NR2A and NR2C subunits of the NMDA receptor increase during the second postnatal wee k. At this time, mRNA and protein levels of the NR2B subunit begin to fall. To investigate targeting of NMDA receptor subunits, we performed whole-cel l recordings from rat cerebellar granule neurons at different times during development and investigated the pharmacological and biophysical properties of mossy fiber-evoked NMDA EPSCs. Isolated NMDA EPSCs from newly formed sy napses in the first postnatal week exhibited partial block by the NR2B subu nit-specific antagonist (1S,2S)-1-(4-hydroxyphenyl)-2-(4-hydroxy-4-phenylpi peridino)-1-propanol (CP 101,606). By the end of the second postnatal week, NMDA EPSCs were virtually unaffected by the NR2B antagonist. In parallel, NMDA EPSC decay times decreased over a similar developmental time course. W e compared properties of synaptic NMDA receptors with extrasynaptic recepto rs that are present on the cell body with rapid application of glutamate to excised nucleated patches. Deactivation of patch responses accelerated wit h development and closely resembled evoked NMDA EPSCs in rats of the same a ge. However, patch responses were highly sensitive to CP 101,606 through th e second postnatal week, and sensitivity was seen in some neurons up to the fourth postnatal week. Spermine potentiated peak NMDA patch responses from postnatal days 10-14 rats but had little effect on evoked NMDA EPSCs. Our data suggest selective targeting of a distinct NMDA receptor subtype to syn aptic receptor populations in cerebellar granule neurons. Later in developm ent, similar changes occur in the extrasynaptic receptor population.