GABAergic signaling in young granule cells in the adult rat and mouse dentate gyrus.
Throughout most of the developing brain, including the hippocampus, GABAergic synapses are the first to become functional. Several features of GABAergic signaling change across development, suggesting that this signaling in the immature brain may play important roles in the growth of young neurons and the establishment of networks. To determine whether GABA(A) receptor (GABA(A)R)-containing synapses in new neurons born in the adult dentate gyrus have similar immature features, we examined spontaneous and evoked GABA(A)R-mediated synaptic currents in young (POMC-EGFP or doublecortin-immunostained) granule cells in acute slice preparations from adult mice and rats. Spontaneous inhibitory postsynaptic currents (IPSCs) were observed in nearly all immature granule cells, but their frequency was considerably lower and their decay time constant was nearly two times longer than in neighboring mature (doublecortin-non-immunoreactive or EGFP-non-expressing) granule cells within the sub-granular zone. Evoked IPSCs (eIPSCs) in mature granule cells, but not immature granule cells, were sensitive to zolpidem, suggesting a maturational increase in GABA(A)R alpha1-subunit expression. Perforated-patch recording revealed that eIPSCs depolarized young neurons, but hyperpolarized mature neurons. The early establishment of synaptic GABAergic inputs slow IPSC decay time, and depolarizing action of eIPSCs are remarkably similar to features previously seen in neurons during development, suggesting that they are intrinsic features of immature neurons and not functions of the surrounding circuitry. These developmental features in adult-born granule cells could play a role in maturational processes such as developmental cell death. However, treatment of adult mice with GABA(A)R agonists and an inverse agonist did not significantly alter the number of 4- to 14-day-old BrdU-labeled cells.
Karten
Yashmin J G
YJ
Unit on Neuroplasticity, NIH, MSC 3718, Bethesda, Maryland 20892-3718, USA.
Jones
Meredith A
MA
Jeurling
Sara I
SI
Cameron
Heather A
HA
D000375:Aging / Q000502:physiology; D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D018891:Dentate Gyrus / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism*; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D018755:GABA Agonists / Q000494:pharmacology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology*; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D009479:Neuropeptides / Q000378:metabolism; D009924:Organ Culture Techniques; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000378:metabolism; D013569:Synapses / Q000187:drug effects / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
C000714848:Dcx protein, rat; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D018755:GABA Agonists; D008869:Microtubule-Associated Proteins; D009479:Neuropeptides; D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid