Transglial transmission at the dorsal root ganglion sandwich synapse: glial cell to postsynaptic neuron communication

The dorsal root ganglion ( DRG ) contains a subset of closely‐apposed neuronal somata ( NS ) separated solely by a thin satellite glial cell ( SGC ) membrane septum to form an NS –glial cell– NS trimer. We recently reported that stimulation of one NS with an impulse train triggers a delayed, noisy and long‐lasting response in its NS pair via a transglial signaling pathway that we term a ‘sandwich synapse’ ( SS ). Transmission could be unidirectional or bidirectional and facilitated in response to a second stimulus train. We have shown that in chick or rat SS the NS ‐to‐ SGC leg of the two‐synapse pathway is purinergic via P 2 Y 2 receptors but the second SGC ‐to‐ NS synapse mechanism remained unknown. A noisy evoked current in the target neuron, a reversal potential close to 0 mV, and insensitivity to calcium scavengers or G protein block favored an ionotropic postsynaptic receptor. Selective block by D‐2‐amino‐5‐phosphonopentanoate (AP5) implicated glutamatergic transmission via N ‐methyl‐ d ‐aspartate receptors. This agent also blocked NS responses evoked by puff of UTP , a P 2 Y 2 agonist, directly onto the SGC cell, confirming its action at the second synapse of the SS transmission pathway. The N ‐methyl‐ d ‐aspartate receptor NR 2 B subunit was implicated by block of transmission with ifenprodil and by its immunocytochemical localization to the NS membrane, abutting the glial septum P 2 Y 2 receptor. Isolated DRG cell clusters exhibited daisy‐chain and branching NS –glial cell– NS contacts, suggestive of a network organization within the ganglion. The identification of the glial‐to‐neuron transmitter and receptor combination provides further support for transglial transmission and completes the DRG SS molecular transmission pathway.