Impact of adult neurogenesis on memory and circuit stability

一个长期以来的教条是，神经发生在早期发育中结束，并且在那之后没有神经元的替换或更替。然而，成年神经发生发生在整个生命中至少两个区域的哺乳动物大脑。其中一个区域，海马体，对学习和记忆至关重要。海马中的成年神经发生以几种方式与学习和记忆相互作用。存在三种主要的相互作用。首先，当新神经元出生后不久就开始学习时，新神经元的存活率会提高。其次，增加新神经元的数量可以改善某些类型的学习和记忆。第三，增加新神经元的数量会导致遗忘先前获得的记忆。但新神经元数量的局部变化如何影响存储在跨许多大脑区域的分布式网络中的记忆的稳定性呢？ 这项研究的目的是确定学习如何影响成人生成的神经元的整合，以及这些新生成的神经元如何不同地影响新旧记忆。我的实验室将研究新神经元对学习相关刺激的突触整合，并确定这些神经元的功能或整体有效性是否会因经验而改变。然后，我们将确定神经发生是否仅通过对局部海马回路的影响来影响学习和记忆，或者神经发生是否也影响海马外网络的活动。新的神经元要存活下来，就必须整合到现有的海马神经回路中。我希望证明，与成熟神经元相比，学习增加了新神经元的突触整合。我预测，这种新的连接将对下游海马和海马外区域的神经元活动产生影响。我假设海马中的新神经元调节海马和海马外电路中稳定性和可塑性的平衡。我进一步预测，这是由于海马体和其他区域之间的功能连接发生变化而导致的下游大脑区域神经元重新激活能力的变化。成人神经发生是海马记忆系统的组成部分。因此，从我的研究项目中获得的信息对于理解一般的学习和记忆机制至关重要。以前的研究只调查了新神经元与海马体本身的相互作用。然而，行为的表现和记忆的回忆是大脑范围内的事件。为了确定神经发生如何调节学习和记忆，有必要检查其对全脑回路的影响。这一点很重要，因为了解学习记忆和遗忘的机制可以用来优化未来的记忆形成。

A long-held dogma was that neurogenesis ended in early development and that there was no replacement or turnover of neurons after that point. However, adult neurogenesis occurs throughout life in at least two regions of the mammalian brain. One of these regions, the hippocampus, is critical for learning and memory. Adult neurogenesis in the hippocampus interacts with learning and memory in several ways. Three main interactions exist. First, the survival of new neurons is enhanced when learning occurs shortly after the new neurons are born. Second, increasing the number of new neurons improves some types of learning and memory. Third, increasing the number of new neurons causes forgetting of previously acquired memories. But how does a localized change in the number of new neurons impact the stability of a memory that is stored in a distributed network across many brain regions? The Goal of this proposal is to determine how learning impacts the integration of adult-generated neurons and in turn how those newly generated neurons differentially influence new and old memories. My lab will examine the synaptic integration of new neurons in response to learning related stimulation and determine whether the function or overall effectiveness of these neurons is altered by experience. We will then determine whether neurogenesis impacts learning and memory solely through effects on local hippocampal circuitry or whether neurogenesis also impacts the activity of extra-hippocampus networks. For new neurons to survive, they must become integrated into the existing hippocampal circuitry. I expect to demonstrate that learning increases the synaptic integration of new neurons compared to mature neurons. I predict that this new connectivity will have an impact on the activity of neurons in downstream hippocampal and extra-hippocampal regions. I hypothesize that new neurons in the hippocampus regulate the balance of stability and plasticity within hippocampal and extra-hippocampal circuitry. I further predict that this occurs from changes in the ability to reactivate neurons in downstream brain regions which may occur due to changes in functional connectivity between the hippocampus and other regions. Adult neurogenesis is an integral component of the hippocampal memory system. Therefore, the information gained from my research program is critical to understanding the mechanisms involved in learning and memory in general. Previous studies have only investigated the interaction of new neurons with the hippocampus itself. However, the manifestation of behaviour and the recall of memories are brain-wide events. To determine how neurogenesis modulates learning and memory it is necessary to examine its effects on brain-wide circuitry. This is important because understanding the mechanisms of learning memory and forgetting could be used to optimize memory formation in the future.