Early Formation of GABAergic Synapses Governs the Development of Adult-Born Neurons in the Olfactory Bulb

被引:42
作者
Pallotto, Marta [1 ,2 ,3 ,4 ]
Nissant, Antoine [1 ,4 ]
Fritschy, Jean-Marc [5 ,6 ]
Rudolph, Uwe [7 ,8 ]
Sassoe-Pognetto, Marco [2 ,3 ]
Panzanelli, Patrizia [2 ,3 ]
Lledo, Pierre-Marie [1 ,4 ]
机构
[1] Inst Pasteur, Percept & Memory Lab, Dept Neurosci, F-75724 Paris 15, France
[2] Univ Turin, Dept Anat Pharmacol & Forens Med, I-10126 Turin, Italy
[3] Univ Turin, Natl Inst Neurosci, I-10126 Turin, Italy
[4] CNRS, Unite Rech Associee 2182, F-75015 Paris, France
[5] Univ Zurich, Inst Pharmacol & Toxicol, CH-8057 Zurich, Switzerland
[6] Ctr Neurosci, CH-8057 Zurich, Switzerland
[7] Harvard Univ, McLean Hosp, Lab Genet Neuropharmacol, Belmont, MA 02478 USA
[8] Harvard Univ, Sch Med, Dept Psychiat, Belmont, MA 02478 USA
基金
瑞士国家科学基金会;
关键词
POSTNATAL SUBVENTRICULAR ZONE; GLUTAMIC-ACID DECARBOXYLASE; GABA(A) RECEPTOR; CRITICAL PERIOD; SYNAPTIC INTEGRATION; PROGENITOR CELLS; NEWBORN NEURONS; GRANULE CELLS; RAT-BRAIN; NEUROGENESIS;
D O I
10.1523/JNEUROSCI.0214-12.2012
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
In mammals, olfactory bulb granule cells (GCs) are generated throughout life in the subventricular zone. GABAergic inputs onto newborn neurons likely regulate their maturation, but the details of this process remain still elusive. Here, we investigated the differentiation, synaptic integration, and survival of adult-born GCs when their afferent GABAergic inputs are challenged by conditional gene targeting. Migrating GC precursors were targeted with Cre-eGFP-expressing lentiviral vectors in mice with a floxed gene encoding the GABA(A) receptor alpha 2-subunit (i.e., Gabra2). Ablation of the alpha 2-subunit did not affect GC survival but dramatically delayed their maturation. We found a reduction in postsynaptic alpha 2-subunit and gephyrin clusters accompanied by a decrease in the frequency and amplitude of GABAergic postsynaptic currents beginning similar to 14 d post-injection (dpi). In addition, mutant cells exhibited altered dendritic branching and spine density. Spine loss appeared with mislocation of glutamatergic synapses on dendritic shafts and a reduction of spontaneous glutamatergic postsynaptic currents, underscoring the relevance of afferent GABAergic transmission for a proper synaptic integration of newborn GCs. To test the role of GABAergic signaling during much early stages of GC maturation, we used a genetic strategy to selectively inactivate Gabra2 in precursor cells of the subventricular zone. In these mice, labeling of newborn GCs with eGFP lentiviruses revealed similar morphological alterations as seen on delayed Gabra2 inactivation in migrating neuroblasts, with reduced dendritic branching and spine density at 7 dpi. Collectively, these results emphasize the critical role of GABAergic synaptic signaling for structural maturation of adult-born GCs and formation of glutamatergic synapses.
引用
收藏
页码:9103 / 9115
页数:13
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