Paracrine intercellular communication by a Ca2+- and SNARE-independent release of GABA and glutamate prior to synapse formation.
GABA and glutamate receptors are expressed in immature "silent" CA1 pyramidal neurons prior to synapse formation, but their function is unknown. We now report the presence of tonic, spontaneous, and evoked currents in embryonic and neonatal CA1 neurons mediated primarily by the activation of GABA(A) receptors. These currents are mediated by a nonconventional release of transmitters, as they persist in the presence of calcium channel blockers or botulinium toxin and are observed in Munc18-1-deficient mice in which vesicular release is abolished. This paracrine communication is modulated by glutamate but not GABA transporters, which do not operate during this period of life. Thus, a Ca(2+)- and SNARE-independent release of transmitters underlies a paracrine mode of communication before synapse formation.
Demarque
Michael
M
Institut de Neurobiologie de la Méditérranée, INMED, Institut de la Santé et de la Recherche Médicale, INSERM U29, Parc Scientifique de Luminy, BP13, 13273 09, Marseille cedex, France.
Represa
Alfonso
A
Becq
Hélène
H
Khalilov
Ilgam
I
Ben-Ari
Yehezkel
Y
Aniksztejn
Laurent
L
D000818:Animals; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology*; D004558:Electric Stimulation; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005333:Fetus; D018756:GABA Antagonists / Q000494:pharmacology; D058787:GABA-A Receptor Antagonists; D018698:Glutamic Acid / Q000378:metabolism*; D006624:Hippocampus / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D019899:Paracrine Communication / Q000502:physiology*; D017966:Pyramidal Cells / Q000166:cytology / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000378:metabolism; D050600:SNARE Proteins; D013569:Synapses / Q000378:metabolism* / Q000648:ultrastructure; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D033921:Vesicular Transport Proteins; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D018691:Excitatory Amino Acid Antagonists; D018756:GABA Antagonists; D058787:GABA-A Receptor Antagonists; D008565:Membrane Proteins; D011963:Receptors, GABA-A; D016194:Receptors, N-Methyl-D-Aspartate; D050600:SNARE Proteins; D033921:Vesicular Transport Proteins; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D002118:Calcium