Physiological contribution of the astrocytic environment of neurons to intersynaptic crosstalk.
PNAS. 2004-02-06; 101(7): 2151-2155
DOI: 10.1073/pnas.0308408100
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1. Proc Natl Acad Sci U S A. 2004 Feb 17;101(7):2151-5. Epub 2004 Feb 6.
Physiological contribution of the astrocytic environment of neurons to
intersynaptic crosstalk.
Piet R(1), Vargová L, Syková E, Poulain DA, Oliet SH.
Author information:
(1)Institut National de la Santé et de la Recherche Médicale Unité 378, Institut
François Magendie, Université Victor Segalen Bordeaux 2, 33077 Bordeaux, France.
Interactions between separate synaptic inputs converging on the same target
appear to contribute to the fine-tuning of information processing in the central
nervous system. Intersynaptic crosstalk is made possible by transmitter spillover
from the synaptic cleft and its diffusion over a distance to neighboring
synapses. This is the case for glutamate, which inhibits gamma-aminobutyric acid
(GABA)ergic transmission in several brain regions through the activation of
presynaptic receptors. Such heterosynaptic modulation depends on factors that
influence diffusion in the extracellular space (ECS). Because glial cells
represent a physical barrier to diffusion and, in addition, are essential for
glutamate uptake, we investigated the physiological contribution of the
astrocytic environment of neurons to glutamate-mediated intersynaptic
communication in the brain. Here we show that the reduced astrocytic coverage of
magnocellular neurons occurring in the supraoptic nucleus of lactating rats
facilitates diffusion in the ECS, as revealed by tortuosity and volume fraction
measurements. Under these conditions, glutamate spillover, monitored through
metabotropic glutamate receptor-mediated depression of GABAergic transmission, is
greatly enhanced. Conversely, impeding diffusion with dextran largely prevents
crosstalk between glutamatergic and GABAergic afferent inputs. Astrocytes,
therefore, by hindering diffusion in the ECS, regulate intersynaptic
communication between neighboring synapses and, probably, overall volume
transmission in the brain.
DOI: 10.1073/pnas.0308408100
PMCID: PMC357067
PMID: 14766975 [Indexed for MEDLINE]