ABSTRACT
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.
Subject(s)
Dentate Gyrus/growth & development , Dentate Gyrus/metabolism , Neural Inhibition/physiology , Neurons/metabolism , Synaptic Transmission/physiology , gamma-Aminobutyric Acid/metabolism , Aging/physiology , Animals , Cell Differentiation/physiology , Cell Division/drug effects , Cell Division/physiology , Dentate Gyrus/cytology , Doublecortin Domain Proteins , Doublecortin Protein , GABA Agonists/pharmacology , Male , Mice , Mice, Transgenic , Microtubule-Associated Proteins/metabolism , Neural Inhibition/drug effects , Neuronal Plasticity/drug effects , Neuronal Plasticity/physiology , Neurons/drug effects , Neuropeptides/metabolism , Organ Culture Techniques , Patch-Clamp Techniques , Rats , Rats, Sprague-Dawley , Receptors, GABA-A/metabolism , Synapses/drug effects , Synapses/metabolism , Synaptic Transmission/drug effectsABSTRACT
Both structure and function of the hippocampus are altered by stress: by increasing levels of corticosteroids, stress causes atrophy of CA3 pyramidal cell dendrites, inhibits adult neurogenesis in the dentate gyrus, and impairs hippocampus-dependent learning. A recent study shows that adverse experience limited to early life, specifically removal of rat pups from their mother for three hours each day, decreases production of new granule neurons in adulthood through a corticosteroid-dependent mechanism. This finding suggests that stress in early life could permanently impair hippocampus-dependent learning and memory and increase susceptibility to depression by inhibiting adult neurogenesis in the hippocampus.
