GABAergic signaling to newborn neurons in dentate gyrus.
Neurogenesis in the dentate gyrus begins before birth but then continues into adulthood. Consequently, many newborn granule cells must integrate into a preexisting hippocampal network. Little is known about the timing of this process or the characteristics of the first established synapses. We used mice that transiently express enhanced green fluorescent protein in newborn granule cells to examine their synaptic input. Although newborn granule cells had functional glutamate receptors, evoked and spontaneous synaptic currents were exclusively GABAergic with immature characteristics including slow rise and decay phases and depolarized reversal potentials. Synaptic currents in newborn granule cells were relatively insensitive to the GABA(A) receptor modulator zolpidem compared with neighboring mature granule cells. Consistent with the kinetics and pharmacology, newborn granule cells isolated by fluorescent cell sorting lacked the alpha1 GABA(A) receptor subunit. Our results indicate that newborn granule cells initially receive only GABAergic synapses even in the adult.
Overstreet Wadiche
Linda
L
Vollum Institute, Oregon Health and Science University, Portland, OR 97239, USA. overstre@ohsu.edu
Bromberg
Daniel A
DA
Bensen
Aesoon L
AL
Westbrook
Gary L
GL
D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D015152:Blotting, Northern / Q000379:methods; D002478:Cells, Cultured; D018891:Dentate Gyrus / Q000166:cytology* / Q000254:growth & development; D004307:Dose-Response Relationship, Radiation; D004558:Electric Stimulation / Q000379:methods; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D005434:Flow Cytometry / Q000379:methods; D005455:Fluorescent Antibody Technique / Q000379:methods; D018755:GABA Agonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D049452:Green Fluorescent Proteins / Q000235:genetics; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D016202:N-Methylaspartate / Q000494:pharmacology; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D010320:Parvalbumins / Q000378:metabolism; D018408:Patch-Clamp Techniques / Q000379:methods; D011333:Pro-Opiomelanocortin / Q000235:genetics; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D011724:Pyridazines / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D011963:Receptors, GABA-A / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D013569:Synapses / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology; D000077334:Zolpidem; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism* / Q000494:pharmacology
D018690:Excitatory Amino Acid Agonists; D018755:GABA Agonists; D018756:GABA Antagonists; D010320:Parvalbumins; D021122:Protein Subunits; D011724:Pyridazines; D011725:Pyridines; D011963:Receptors, GABA-A; D049452:Green Fluorescent Proteins; D005680:gamma-Aminobutyric Acid; D016202:N-Methylaspartate; D011333:Pro-Opiomelanocortin; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D000077334:Zolpidem; C049853:gabazine