Astrocyte mediated neuronal synchronization properties revealed by false gliotransmitter release

Abstract

Astrocytes spontaneously release glutamate as a gliotransmitter (GT) resulting in the generation of extrasynaptic NMDA-R mediated slow inward currents (SICs) in neighbouring neurons, which can increase local neuronal excitability. However, there is a deficit in our knowledge of the factors that control spontaneous astrocyte GT release, and the extent of its influence. We found that in rat brain slices, increasing the supply of the physiological transmitter glutamate increased the frequency and signalling charge of SICs over an extended period. This phenomenon was replicated by exogenous pre-exposure to the amino acid D-Aspartate. Using D-Aspartate as a “False” GT we determined the extent of local neuron excitation by GT release in VB thalamus, CA1 hippocampus and somatosensory cortex. By analysing synchronised neuronal NMDA-R mediated excitation we found that the properties of the excitation were conserved in different brain areas. In the three areas, astrocyte derived GT release synchronised groups of neurons at distances of over 200μm. Individual neurons participated in more than one synchronised population, indicating that individual neurons can be excited by more than one astrocyte, and that individual astrocytes may determine a neuron's synchronised network. The results confirm that astrocytes can act as excitatory nodes that can influence neurons over a significant range in a number of brain regions. Our findings further suggest that chronic elevation of ambient glutamate levels can lead to increased gliotransmitter glutamate release, which may be relevant in some pathological states.