Presynaptic but not postsynaptic GABA signaling at unitary mossy fiber synapses.
Dentate gyrus granule cells have been suggested to corelease GABA and glutamate both in juvenile animals and under pathological conditions in adults. Although mossy fiber terminals (MFTs) are known to express glutamic acid decarboxylase (GAD) in early postnatal development, the functional role of GABA synthesis in MFTs remains controversial, and direct evidence for synaptic GABA release from MFTs is missing. Here, using GAD67-GFP transgenic mice, we show that GAD67 is expressed only in a population of immature granule cells in juvenile animals. We demonstrate that GABA can be released from these cells and modulate mossy fiber excitability through activation of GABAB autoreceptors. However, unitary postsynaptic currents generated by individual, GAD67-expressing granule cells are purely glutamatergic in all postsynaptic cell types tested. Thus GAD67 expression does not endow dentate gyrus granule cells with a full GABAergic phenotype and GABA primarily instructs the pre- rather than the postsynaptic element.
INSERM, UMR 839, F75005, Paris, France. carolina.cabezas@icm-institute.org
Carolina
C
Cabezas
Theano
T
Irinopoulou
Grégory
G
Gauvain
Jean Christophe
JC
Poncer
D000818:Animals; D000831:Animals, Newborn; D001514:Bee Venoms / Q000494:pharmacology; D002352:Carrier Proteins / Q000378:metabolism; D027682:Cation Transport Proteins; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000235:genetics; D007839:Functional Laterality / Q000502:physiology*; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels / Q000378:metabolism; D018756:GABA Antagonists / Q000494:pharmacology; D005968:Glutamate Decarboxylase / Q000235:genetics; D049452:Green Fluorescent Proteins / Q000235:genetics; D006624:Hippocampus / Q000166:cytology*; D018398:Homeodomain Proteins / Q000378:metabolism; D021621:Imaging, Three-Dimensional; D066298:In Vitro Techniques; D008565:Membrane Proteins / Q000378:metabolism; D026901:Membrane Transport Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D019599:Mossy Fibers, Hippocampal / Q000187:drug effects / Q000378:metabolism*; D009474:Neurons / Q000166:cytology* / Q000187:drug effects; D010721:Phosphinic Acids / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D017729:Presynaptic Terminals / Q000187:drug effects / Q000502:physiology*; D011412:Propanolamines / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D025521:Tumor Suppressor Proteins / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*; D000098551:Prospero-Related Homeobox 1 Protein
D001514:Bee Venoms; D002352:Carrier Proteins; D027682:Cation Transport Proteins; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; D018756:GABA Antagonists; D018398:Homeodomain Proteins; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D010721:Phosphinic Acids; D026902:Potassium Channel Blockers; D011412:Propanolamines; C491177:Slc30a3 protein, mouse; D025521:Tumor Suppressor Proteins; C485184:enhanced green fluorescent protein; D000098551:Prospero-Related Homeobox 1 Protein; D049452:Green Fluorescent Proteins; C085075:CGP 55845A; C029738:tertiapin; D005680:gamma-Aminobutyric Acid; D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1