Metabotropic glutamate receptor-mediated control of neurotransmitter release.
Presynaptic metabotropic glutamate receptors (mGluRs) modulate the release of transmitter from most central synapses. However, difficulties in recording from presynaptic structures has lead to an incomplete understanding of the mechanisms underlying these fundamental processes. By recording directly from presynaptic reticulospinal axons and postsynaptic motoneurons of the lamprey spinal cord, we have obtained electrophysiological and optical evidence that vertebrate presynaptic metabotropic glutamate receptors modulate neurotransmitter release at this synapse through two distinct mechanisms: (1) mGluR activation in the presynaptic terminal depresses transmitter release by activating a presynaptic K+ current, and (2) mGluR activation enhances transmitter release by amplifying the action potential-evoked presynaptic Ca2+ signal by rapidly releasing Ca2+ from intracellular stores in a Ca2+-dependent manner. Furthermore, this effect is mediated by physiological release of glutamate from the presynaptic terminals. These autoreceptor-mediated processes are likely to generate complex effects on transmitter release evoked by repetitive stimulation.
Cochilla
A J
AJ
Department of Physiology, Northwestern University Medical School, Northwestern University Institute for Neuroscience, Chicago, Illinois 60611, USA.
Alford
S
S
D015761:4-Aminopyridine / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D003515:Cycloleucine / Q000031:analogs & derivatives / Q000494:pharmacology; D004594:Electrophysiology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005998:Glycine / Q000031:analogs & derivatives / Q000494:pharmacology; D007798:Lampreys; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009046:Motor Neurons / Q000737:chemistry / Q000502:physiology / Q000648:ultrastructure; D018696:Neuroprotective Agents / Q000494:pharmacology; D018377:Neurotransmitter Agents / Q000378:metabolism*; D011188:Potassium / Q000378:metabolism; D017729:Presynaptic Terminals / Q000737:chemistry / Q000187:drug effects / Q000502:physiology; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists / Q000378:metabolism*; D012118:Resorcinols / Q000494:pharmacology; D012433:Ryanodine / Q000494:pharmacology; D013116:Spinal Cord / Q000166:cytology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*
D018691:Excitatory Amino Acid Antagonists; D018696:Neuroprotective Agents; D018377:Neurotransmitter Agents; D018094:Receptors, Metabotropic Glutamate; D012118:Resorcinols; D003515:Cycloleucine; C036361:1-amino-1,3-dicarboxycyclopentane; D012433:Ryanodine; C079215:3,5-dihydroxyphenylglycine; D015761:4-Aminopyridine; D011188:Potassium; D002118:Calcium; D005998:Glycine