Long-term potentiation depends on release of D-serine from astrocytes
Nature. 2010-01-14; 463(7278): 232-236
DOI: 10.1038/nature08673
Lire sur PubMed
1. Nature. 2010 Jan 14;463(7278):232-6. doi: 10.1038/nature08673.
Long-term potentiation depends on release of D-serine from astrocytes.
Henneberger C(1), Papouin T, Oliet SH, Rusakov DA.
Author information:
(1)UCL Institute of Neurology, University College London, London WC1N 3BG, UK.
Comment in
Nature. 2010 Jan 14;463(7278):169-70.
Long-term potentiation (LTP) of synaptic transmission provides an experimental
model for studying mechanisms of memory. The classical form of LTP relies on
N-methyl-D-aspartate receptors (NMDARs), and it has been shown that astroglia can
regulate their activation through Ca(2+)-dependent release of the NMDAR
co-agonist D-serine. Release of D-serine from glia enables LTP in cultures and
explains a correlation between glial coverage of synapses and LTP in the
supraoptic nucleus. However, increases in Ca(2+) concentration in astroglia can
also release other signalling molecules, most prominently glutamate, ATP and
tumour necrosis factor-alpha, whereas neurons themselves can synthesize and
supply D-serine. Furthermore, loading an astrocyte with exogenous Ca(2+) buffers
does not suppress LTP in hippocampal area CA1 (refs 14-16), and the physiological
relevance of experiments in cultures or strong exogenous stimuli applied to
astrocytes has been questioned. The involvement of glia in LTP induction
therefore remains controversial. Here we show that clamping internal Ca(2+) in
individual CA1 astrocytes blocks LTP induction at nearby excitatory synapses by
decreasing the occupancy of the NMDAR co-agonist sites. This LTP blockade can be
reversed by exogenous D-serine or glycine, whereas depletion of D-serine or
disruption of exocytosis in an individual astrocyte blocks local LTP. We
therefore demonstrate that Ca(2+)-dependent release of D-serine from an astrocyte
controls NMDAR-dependent plasticity in many thousands of excitatory synapses
nearby.
DOI: 10.1038/nature08673
PMCID: PMC2807667
PMID: 20075918 [Indexed for MEDLINE]