Physiological contribution of the astrocytic environment of neurons to intersynaptic crosstalk

Abstract

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 ␥-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.

Astrocytes Impose Postburst Depression of Release Probability at Hippocampal Glutamate Synapses

“…Spillover, on the other hand, would rather be expected to be favored early in development when astrocyte processes around synapses and glutamate uptake are poorly developed (Piet et al, 2004;Diamond, 2005). The developmental profile of the PBD (Fig.…”

Morphological plasticity of astroglia: Understanding synaptic microenvironment

“…Astrocytic coverage is reduced and this leads to an enhanced number of synapses and neurotransmitter spillover (Hatton, 1997; Piet et al, 2004a; Theodosis and Poulain, 1993). With the reduction of astrocytic synapse enwrapping also glutamate clearance is reduced which in turn leads to enhanced negative feedback on glutamate release and increased heterosynaptic depression of GABA release (Oliet et al, 2001; Piet et al, 2004b) and prolonged excitatory postsynaptic potentials (EPSPs) in the cerebellum (Iino et al, 2001). Additionally, in such cases, less d ‐serine may be available from astrocytes for the co‐agonist activation of postsynaptic NMDARs and thus the machinery of long‐term synaptic plasticity in the SON (Panatier et al, 2006).…”

Hallucinogen-Induced UP States in the Brain Slice of Rat Prefrontal Cortex: Role of Glutamate Spillover and NR2B-NMDA Receptors

“…Physiological variations in glial coverage have been shown to alter glutamate diffusion in the extracellular space (Piet et al, 2004). The ability of psychedelic hallucinogens to enhance either spillover, or detection of spillover, in the prefrontal cortical slice may arise from the density of 5-HT 2A receptors on apical dendrites of layer V neurons (Blue et al, 1988;Cornea-Hebert et al, 1999;Hamada et al, 1998;Jakab and Goldman-Rakic, 1998;Willins et al, 1997;Xu and Pandey, 2000;Miner et al, 2003), together with the arrangement of these apical dendrites in bundles (Gabbott and Bacon, 1996;Skoglund et al, 2004).…”

“…First, we retard the diffusion of glutamate beyond the synapse by changing the viscosity of the extracellular space using dextran, a macromolecule that has often been employed to suppress spillover (Min et al, 1998;Perrais and Ropert, 2000;Nielsen et al, 2004;Piet et al, 2004;Savtchenko and Rusakov, 2005). Then, we assess the subtypes of NMDA receptors that are involved in the delayed wave of glutamate enhanced by psychedelic hallucinogens.…”