Biphasic modulation of GABA release from stellate cells by glutamatergic receptor subtypes.
The release of inhibitory transmitters from CNS neurons can be modulated by ionotropic glutamate receptors that are present in the presynaptic terminals. In the cerebellum, glutamate released from climbing fibers (but not from parallel fibers) activates presynaptic AMPA receptors and suppresses the release of the inhibitory transmitter GABA from basket cells onto postsynaptic Purkinje cells. This input-specific modulation has been attributed to the close proximity of the climbing fibers to the axons of the basket cells. Our recent work indicates that glutamate released from parallel fibers can "spill over" and reach the axons of stellate cells. Here I test the possibility that this spillover glutamate can activate presynaptic AMPA receptors in stellate cells and in this way modulate their release of GABA. I find that stimulation of parallel fibers activates AMPA receptors and transiently suppresses autoreceptor and autaptic GABAergic currents in stellate cells. Activation of AMPA receptors reduces the release of GABA and the suppression occurs more frequently in immature cells that have a high release probability. By contrast the release of GABA from mature stellate cells that have a low release probability is potentiated by the activation of NMDA-type glutamate receptors on presynaptic terminals. Thus during development, the glutamatergic modulation of GABA release switches from an AMPA-receptor-mediated transient suppression to a NMDA-receptor-induced lasting potentiation.
Liu
Siqiong June
SJ
Department of Biology, Mueller Laboratory, Penn State University, State College, PA 16802, USA. sjl16@psu.edu
D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D002531:Cerebellum / Q000166:cytology; D004307:Dose-Response Relationship, Radiation; D004558:Electric Stimulation; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D066298:In Vitro Techniques; D053444:Inhibitory Postsynaptic Potentials / Q000187:drug effects / Q000528:radiation effects; D007395:Interneurons / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D009025:Morpholines / Q000494:pharmacology; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D018408:Patch-Clamp Techniques / Q000379:methods; D010880:Piperidines / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D018091:Receptors, AMPA / Q000502:physiology*; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
C095804:(+)-(S)-5,5-dimethylmorpholinyl-2-acetic acid; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D018756:GABA Antagonists; D009025:Morpholines; D010880:Piperidines; D011720:Pyrazoles; D011810:Quinoxalines; D018091:Receptors, AMPA; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline; C103505:AM 251; D005680:gamma-Aminobutyric Acid; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid