MAPPING CONNECTIVITY ONTO POSTNATAL-BORN NEURONS

持续的神经发生是成人大脑细胞和结构神经可塑性的一种显著方式 组织，并阐明了支持和引导这一现象的基本机制 制定未来修复受损或患病神经组织的方法。数据具有 表明许多外在的生理和病理过程直接影响成人的神经发生。 以及新生神经元的突触整合。值得注意的是，神经活动的增加增强了成人的神经发生， 突触发生和回路重塑，而神经活动减少或改变会损害新生儿 神经元的存活和整合。然而，到目前为止，传达依赖活动的输入的身份发生了变化 到新生神经元，它们对活动操纵的反应信号的性质直到现在才 开始显露出来。在本奖项的前一次授权期内，我们已经确定了以前未知的 输入的来源，并揭示了有助于活动的新的神经调节信号机制- 成人大脑中新生神经元的依赖连接。在这里，我们将对这些发现进行扩展，以更好地 了解促进成人脑内新突触形成和稳定的细胞机制 组织，并进一步分析操纵这些通路如何影响新脑的形成和/或重塑 电路。

Continued neurogenesis represents a remarkable means of cellular and structural neural plasticity in adult brain tissue, and elucidating the fundamental mechanisms that support and guide this phenomenon holds promise towards developing future approaches towards repairing damaged or diseased nervous tissue. Data have shown that numerous extrinsic physiological and pathological processes directly influence adult neurogenesis and synaptic integration of newborn neurons. Notably, increased neural activity enhances adult neurogenesis, synaptogenesis, and circuit remodeling, whereas decreased or altered neural activity compromises newborn neuron survival and integration. To date however, the identities of inputs that convey activity-dependent changes to newborn neurons, and the nature of their signaling in response to activity manipulations are only now beginning to be revealed. In the previous granting period of this award, we have identified previously unknown sources of input, and revealed novel neuromodulatory signaling mechanisms that contribute towards the activity- dependent wiring of newborn neurons in the adult brain. Here we will expand upon these findings to better understand the cellular mechanisms that promote the formation and stabilization of new synapses in adult brain tissue, and further assay how manipulating these pathways affects the formation and/or remodeling of new brain circuits.