The Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Neuron. 2010 Jan 14;65(1):32-9. doi: 10.1016/j.neuron.2009.12.001.
New neurons are added to the adult brain throughout life, but only half ultimately integrate into existing circuits. Sensory experience is an important regulator of the selection of new neurons but it remains unknown whether experience provides specific patterns of synaptic input or simply a minimum level of overall membrane depolarization critical for integration. To investigate this issue, we genetically modified intrinsic electrical properties of adult-generated neurons in the mammalian olfactory bulb. First, we observed that suppressing levels of cell-intrinsic neuronal activity via expression of ESKir2.1 potassium channels decreases, whereas enhancing activity via expression of NaChBac sodium channels increases survival of new neurons. Neither of these modulations affects synaptic formation. Furthermore, even when neurons are induced to fire dramatically altered patterns of action potentials, increased levels of cell-intrinsic activity completely blocks cell death triggered by NMDA receptor deletion. These findings demonstrate that overall levels of cell-intrinsic activity govern survival of new neurons and precise firing patterns are not essential for neuronal integration into existing brain circuits.
新神经元在整个成年期不断添加到大脑中，但最终只有一半整合到现有的电路中。感觉经验是新神经元选择的重要调节因子，但尚不清楚经验提供的是新神经元选择的特定突触输入模式，还是对于整合至关重要的最小整体膜去极化水平。为了研究这个问题，我们在哺乳动物嗅球中对成年产生的神经元的内在电特性进行了基因修饰。首先，我们观察到通过表达 ESKir2.1 钾通道抑制细胞内在神经元活动水平会减少新神经元的存活，而通过表达 NaChBac 钠通道增强活动则会增加新神经元的存活。这两种调节都不会影响突触形成。此外，即使神经元被诱导以剧烈改变的动作电位模式放电，增加细胞内在活动水平也会完全阻止 NMDA 受体缺失触发的细胞死亡。这些发现表明，细胞内在活动的总体水平决定了新神经元的存活，而精确的放电模式对于神经元整合到现有的大脑电路中并不是必需的。
