Increased cell-intrinsic excitability induces synaptic changes in new neurons in the adult dentate gyrus that require Npas4.
Increased cell-intrinsic excitability induces synaptic changes in new neurons in the adult dentate gyrus that require Npas4.
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DOI：
10.1523/jneurosci.1571-12.2013
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发表时间：
2013-05-01
期刊：
影响因子：
--
通讯作者：
Lois C
中科院分区：
文献类型：
--
作者：
Sim S;Antolin S;Lin CW;Lin Y;Lois C
电活动调节神经元成熟和相互连接的方式。然而，目前尚不清楚单细胞活性的增加是否足以改变该神经元突触连接的发展，或者是否有必要全面增加电路活动。为了解决这个问题，我们通过表达电压门控细菌钠通道，在体内增加了小鼠齿状回中单个成年出生神经元的神经元兴奋性。我们观察到，在一个原本不受干扰的回路中，增加新神经元的兴奋性会导致它们的输入突触和轴突突触的变化。此外，依赖活性的转录因子Npas4对于这些神经元的输入突触的变化是必要的，但它并不参与轴突突触的变化。我们的结果表明，成熟过程中细胞内在活性的增加足以改变神经元与海马电路的突触连接，而Npas4是输入突触活动依赖的变化所必需的。
Electrical activity regulates the manner in which neurons mature and form connections to each other. However, it remains unclear whether increased single-cell activity is sufficient to alter the development of synaptic connectivity of that neuron or if a global increase in circuit activity is necessary. To address this question, we genetically increased neuronal excitability of in vivo individual adult-born neurons in the mouse dentate gyrus via expression of a voltage-gated bacterial sodium channel. We observed that increasing the excitability of new neurons in an otherwise unperturbed circuit leads to changes in both their input and axonal synapses. Furthermore, the activity-dependent transcription factor Npas4 is necessary for the changes in these neurons’ input synapses, but it is not involved in changes to their axonal synapses. Our results reveal that an increase in cell-intrinsic activity during maturation is sufficient to alter a neuron’s synaptic connectivity with the hippocampal circuit, and that Npas4 is required for activity-dependent changes in input synapses.