Circuit and cellular mechanisms of adult neurogenesis in context encoding and discrimination

项目总结 成年海马结构的齿状回亚区表现出一种独特的可塑性，即 在整个生命过程中产生新的神经元。这些成体出生的颗粒细胞(AbGC)整合到现有的回路中。 并在其发育的特定阶段具有不同的特性。成人神经发生的这个过程是 受环境和情绪状态的动态调节；对情绪有负面影响的干预， 如压力和隔离可以降低神经发生的水平，而提高情绪的干预措施，如 因为营养丰富和锻炼可以增加神经发生的水平。在行为上，这些abgc一直是 涉及认知功能，如学习和记忆，以及与情绪相关的功能，如 对应激或抗抑郁治疗的反应。然而，我们对射击缺乏完整的了解 自由行为小鼠abGC的模式，其动态编码模式与成熟GC的不同 (MGCS)以及环境如何改变体内的这些活动模式。在这里，我们将讨论这些长期的- 田野上的悬而未决的问题。使用新颖、尖端的工具来监控和操纵 在活体内年龄匹配的abGC队列中，我们将询问这些神经元对海马区功能的贡献 在它们的发育过程中。首先，我们将使用细胞类型的特定光学技术来使特定的队列保持沉默 这些神经元在语境编码和辨别阶段。那我们就用功能钙吧。 在自由活动的小鼠中进行成像，以确定abGC在这些上下文编码和 差异化。最后，我们将确定环境的丰富和锻炼如何改变发射模式。 以及体内abGC和DG-CA3电路的编码特性。这些研究的目标是了解 在恐惧记忆形成过程中，这些神经元对语境表征进行编码的机制。 了解abGC在这一过程中的作用可能会使我们能够利用这种独特的可塑性形式 成人大脑，用于治疗恐惧和焦虑相关的障碍。

Project summary The dentate gyrus subfield of the adult hippocampal formation exhibits a unique form of plasticity, the ability to generate new neurons throughout life. These adult born granule cells (abGCs) integrate into existing circuitry and have distinct properties during specific phases of their development. This process of adult neurogenesis is dynamically regulated by environment and emotional state; interventions that have negative effects on mood, such as stress and isolation can reduce levels of neurogenesis, while interventions that increase mood, such as enrichment and exercise can increase levels of neurogenesis. Behaviorally, these abGCs have been implicated in cognitive functions such as learning and memory, as well as mood related functions such as responses to stress or antidepressant treatment. However, we lack a complete understanding of the firing patterns of abGCs in freely behaving mice, how their dynamic encoding patterns differ from mature GCs (mGCs) and how environment may alter these activity patterns in vivo. Here we will address these long- standing questions in the field. Using novel, cutting-edge tools for monitoring and manipulating the activity of age-matched cohorts of abGCs in vivo, we will ask how these neurons contribute to hippocampal function during their development. First, we will use cell-type specific optical techniques to silence specific cohorts of these neurons during phases of context encoding and discrimination. Then we will use functional calcium imaging in freely moving mice to determine how abGCs function during these tests of context encoding and differentiation. Finally, we will determine how environmental enrichment and exercise alter the firing patterns and encoding properties of abGCs and the DG- CA3 circuit in vivo. The goal of these studies is to understand the mechanisms by which these neurons encode contextual representations during fear memory formation. Understanding the role of abGCs in this process may allow us to harness this unique form of plasticity in the adult brain for the treatment of fear and anxiety- related disorders.