The concept of the tripartite synapse, whereby astrocytes actively modulate the communication between the pre- and postsynaptic site, is widely accepted. The release of gliotransmitters has been linked to release of Ca2÷ from intracellular stores through the activation of astrocytic metabotropic glutamate receptor 5 (mGluR5) by glutamate spillover from synapses. However, nearly all studies on the tripartite synapse have used brain tissue collected from young individuals. Many receptors undergo changes in expression level during development. Sun et al. (see the Perspective by Grosche and Reichenbach) applied genomic analysis, electron microscopy, and calcium imaging in slices and in vivo to assess the presence and the functionality of mGluR5 and mGluR3 receptors during postnatal development in human and mouse astrocytes. Astrocytic expression of mGluR5 was lost by the third postnatal week in mice and was not present in human cortical astrocytes, which calls into question the viability of the tripartite synapse model for adult synapses.
W. Sun, E. McConnell, J.-F. Pare, Q. Xu, M. Chen, W. Peng, D. Lovatt, X. Han, Y. Smith, M. Nedergaard, Glutamate-dependent neuroglial calcium signaling differs between young and adult brain. Science 339, 197–200 (2013). [Abstract] [Full Text]