Glial cells decipher synaptic competition at the mammalian neuromuscular junction.

It is now accepted that glial cells actively interact with neurons and modulate their activity in many regions of the nervous system. Importantly, modulation of synaptic activity by glial cells depends on the proper detection and decoding of synaptic activity. However, it remains unknown whether glial cells are capable of decoding synaptic activity and properties during early postdevelopmental stages, in particular when different presynaptic nerve terminals compete for the control of the same synaptic site. This may be particularly relevant because a major determinant of the outcome of synaptic competition process is the relative synaptic strength of competing terminals whereby stronger terminals are more likely to occupy postsynaptic territory and become stabilized while weaker terminals are often eliminated. Hence, because of their ability to decode synaptic activity, glial cells should be able to integrate neuronal information of competing terminals. Using simultaneous glial Ca(2+) imaging and synaptic recordings of dually innervated mouse neuromuscular junctions, we report that single glial cells decipher the strength of competing nerve terminals. Activity of single glial cells, revealed by Ca(2+) responses, reflects the synaptic strength of each competing nerve terminal and the state of synaptic competition. This deciphering is mediated by functionally segregated purinergic receptors and intrinsic properties of glial cells. Our results indicate that glial cells decode ongoing synaptic competition and, hence, are poised to influence its outcome.