Role for Astrocytes in mGluR-Dependent LTD in the Neocortex and Hippocampus

Astroglia are an active element of brain plasticity, capable to release small molecule gliotransmitters by various mechanisms and regulate synaptic strength. While importance of glia-neuron communications for long-term potentiation has been rather widely reported, research into role for astrocytes in long-depression (LTD) is just gaining momentum. Here, we explored the role for astrocytes in the prominent form of synaptic plasticity-mGluR-dependent LTD. We found out the substantial contribution of the Group I receptors, especially mGluR1 subtype, into Ca²⁺-signaling in hippocampal and neocortical astrocytes, which can be activated during synaptic stimulation used for LTD induction. Our data demonstrate that mGluR receptors can activate SNARE-dependent release of ATP from astrocytes which in turn can directly activate postsynaptic P2X receptors in the hippocampal and neocortical neurons. The latter mechanism has recently been shown to cause the synaptic depression via triggering the internalisation of AMPA receptors. Using mouse model of impaired glial exocytosis (dnSNARE mice), we demonstrated that mGluR-activated release of ATP from astrocytes is essential for regulation of mGluR-dependent LTD in CA3-CA1 and layer 2/3 synapses. Our data also suggest that astrocyte-related pathway relies mainly on mGluR1 receptors and act synergistically with neuronal mechanisms dependent mainly on mGluR5.