MAPPING CONNECTIVITY ONTO POSTNATAL-BORN NEURONS

持续的神经发生是成年脑细胞和结构神经可塑性的一种显著方式 组织，并阐明支持和指导这一现象的基本机制， 致力于开发未来修复受损或患病神经组织的方法。数据具有 许多外在的生理和病理过程直接影响成年神经发生 和新生神经元的突触整合。值得注意的是，增加的神经活动增强了成年神经发生， 突触发生和电路重塑，而减少或改变的神经活动损害新生儿 神经元存活和整合。然而，迄今为止，传递活动依赖性变化的输入的标识 新生神经元，以及它们对活动操纵的信号响应的性质， 开始被揭露。在本奖项的前一个授予期，我们发现了以前未知的 输入的来源，并揭示了新的神经调节信号机制，有助于活动- 成人大脑中新生神经元的依赖性连接。在这里，我们将扩展这些发现，以更好地 了解促进成人大脑中新突触形成和稳定的细胞机制 组织，并进一步分析如何操纵这些途径影响新的大脑的形成和/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.