Presynaptic modulation of parallel fibre signalling to Bergmann glia.
Transmission at the parallel fibre-Purkinje neurone synapse of the cerebellum can be depressed by a number of presynaptic receptors: endocannabinoid (CB1), metabotropic glutamate (mGluR4), adenosine (A1) and GABA (GABA(B)), which have been implicated in both short- and long-term synaptic plasticity. Stimulation of parallel fibres also activates glutamate receptors and transporters on the Bergmann glial cell that forms a sheath around the synapse. The resulting glial extrasynaptic currents (ESC) exhibit short- and long-term plasticity, which differs from the plasticity of adjacent synapses. This functional independence could arise from differential modulation of presynaptic release sites targeted to synapses or glia, but the sensitivity of glial ESC to these inhibitory pathways is unknown. Here I show that all four presynaptic receptors depress parallel fibre-Bergmann glial cell signalling with similar potency to synaptic transmission. Depression of glial ESC is accompanied by a decrease in paired pulse ratio. However, application of receptor antagonists had no effect on ESC amplitude, indicating that tonic activation of these pathways does not occur, and antagonists failed to block the activity-dependent depression of glial ESC observed during tetanic or low frequency stimulation. These data suggest that modulation of presynaptic glutamate release does not underlie glial plasticity.
Bellamy
Tomas C
TC
The Babraham Institute, Babraham, Cambridge CB2 4AT, UK. tom.bellamy@bbsrc.ac.uk
D000818:Animals; D000831:Animals, Newborn; D048588:Benzoxazines; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002531:Cerebellum / Q000166:cytology*; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D004347:Drug Interactions; D004558:Electric Stimulation / Q000379:methods; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018757:GABA Modulators / Q000494:pharmacology; D066298:In Vitro Techniques; D020128:Inhibitory Concentration 50; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D009025:Morpholines / Q000494:pharmacology; D009281:Naphthalenes / Q000494:pharmacology; D009412:Nerve Fibers / Q000502:physiology* / Q000528:radiation effects; D009457:Neuroglia / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D018408:Patch-Clamp Techniques / Q000379:methods; D017729:Presynaptic Terminals / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D051381:Rats; D013997:Time Factors; D014970:Xanthines / Q000494:pharmacology
D048588:Benzoxazines; D002121:Calcium Channel Blockers; D018690:Excitatory Amino Acid Agonists; D018757:GABA Modulators; D009025:Morpholines; D009281:Naphthalenes; D014970:Xanthines; C070417:(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone; C051360:1,3-dipropyl-8-cyclopentylxanthine