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

• Published in: The European journal of neuroscience Vol. 37; no. 8; pp. 1221 - 1228
• Main Authors: Rozanski, Gabriela M., Li, Qi, Stanley, Elise F.
• Format: Journal Article
• Language: English
• Published: Oxford Blackwell Publishing Ltd 01.04.2013; Blackwell
• Subjects: Animals; Biological and medical sciences; Chick Embryo; dorsal root ganglion; Fundamental and applied biological sciences. Psychology; Ganglia, Spinal - metabolism; glutamatergic; Immunohistochemistry; N-methyl-d-aspartate receptor; Neuroglia - metabolism; Neurons - metabolism; NR2B; Patch-Clamp Techniques; Rats; Receptors, N-Methyl-D-Aspartate - metabolism; Signal Transduction - physiology; Synaptic Transmission - physiology; Vertebrates: nervous system and sense organs; Spinal cord; Glial cell; Neuroglia; glutamatergic; Central nervous system; Glutamate receptor; NR2B; Synapse; dorsal root ganglion; N-methyl-D-aspartate receptor; Spinal ganglion; Postsynaptic neuron; NMDA receptor
• ISSN: 0953-816X; 1460-9568
• DOI: 10.1111/ejn.12132

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 P2Y2 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 P2Y2 agonist, directly onto the SGC cell, confirming its action at the second synapse of the SS transmission pathway. The N‐methyl‐d‐aspartate receptor NR2B subunit was implicated by block of transmission with ifenprodil and by its immunocytochemical localization to the NS membrane, abutting the glial septum P2Y2 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. The DRG contains a subset of neuronal somata ‘Sandwich Synapse’ pairs separated by single glial membrane septum. Stimulation of one soma triggers a delayed response in its pair (EJN 2012a) via a bi‐synaptic, neuron‐glia‐neuron pathway (diagram). Neuron‐to‐glial transmission is purinergic via P2Y2 receptors (EJN 2012b). Here we show the glial‐to‐neuron synapse is glutamatergic via NMDA receptors and is blocked by AP3 or ifenprodil (lower panel), completing the synaptic pathway.