Impact of adult neurogenesis on memory and circuit stability

点击翻译按钮获取中文摘要

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.