Paracrine intercellular communication by a Ca2+- and SNARE-independent release of GABA and glutamate prior to synapse formation

Michael Demarque; Alfonso Represa; Hélène Becq; Ilgam Khalilov; Yehezkel Ben-Ari; Laurent Aniksztejn

doi:10.1016/s0896-6273(02)01053-x

Paracrine intercellular communication by a Ca2+- and SNARE-independent release of GABA and glutamate prior to synapse formation

Neuron. 2002 Dec 19;36(6):1051-61. doi: 10.1016/s0896-6273(02)01053-x.

Authors

Michael Demarque¹, Alfonso Represa, Hélène Becq, Ilgam Khalilov, Yehezkel Ben-Ari, Laurent Aniksztejn

Affiliation

¹ 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.

PMID: 12495621
DOI: 10.1016/s0896-6273(02)01053-x

Abstract

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.

MeSH terms

Animals
Calcium / metabolism
Calcium Signaling / physiology
Cell Differentiation / physiology*
Electric Stimulation
Excitatory Amino Acid Antagonists / pharmacology
Fetus
GABA Antagonists / pharmacology
GABA-A Receptor Antagonists
Glutamic Acid / metabolism*
Hippocampus / cytology
Hippocampus / embryology*
Hippocampus / metabolism
Membrane Potentials / drug effects
Membrane Potentials / physiology
Membrane Proteins / metabolism
Mice
Mice, Knockout
Paracrine Communication / physiology*
Pyramidal Cells / cytology
Pyramidal Cells / metabolism*
Rats
Rats, Wistar
Receptors, GABA-A / metabolism
Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors
Receptors, N-Methyl-D-Aspartate / metabolism
SNARE Proteins
Synapses / metabolism*
Synapses / ultrastructure
Synaptic Transmission / drug effects
Synaptic Transmission / physiology
Vesicular Transport Proteins*
gamma-Aminobutyric Acid / metabolism*

Substances

Excitatory Amino Acid Antagonists
GABA Antagonists
GABA-A Receptor Antagonists
Membrane Proteins
Receptors, GABA-A
Receptors, N-Methyl-D-Aspartate
SNARE Proteins
Vesicular Transport Proteins
Glutamic Acid
gamma-Aminobutyric Acid
Calcium