The impact of interneuron plasticity on engram and memory formation in the hippocampus

中间神经元可塑性对海马印迹和记忆形成的影响

• 批准号: 262040908
• 负责人: Professor Dr. Peer Wulff
• 金额: --
• 依托单位: Physiologisches Institut
• 依托单位国家: 德国
• 项目类别: Research Units
• 财政年份: 2014
• 资助国家: 德国
• 起止时间: 2013-12-31 至 2022-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/262040908?language=en
• 关键词: impact; interneuron; plasticity; engram; memory

Principal cells are viewed as the processing units of brain computations. They encode information in their activity patterns and communicate this information to other local or distant principal cells. In addition, principal cells show experience-dependent functional and structural changes in synaptic transmission and connectivity. Such plasticity allows the organism to adapt to new situations and to form memories. Principal cell activity, however, is tightly regulated in time and space by various types of inhibitory GABAergic interneurons. A number of recent studies, including some from our research unit (RU), have shown that contrary to a long standing belief synapses onto interneurons (INs) are also subject to strong plastic changes. This is highly relevant as changes in the connectivity or recruitment of GABAergic inhibitory cells may have profound effects on the temporal and spatial activity patterns of principal cells. During the first funding period of the research unit we were able to demonstrate for the first time that perisomatic-targeting parvalbumin (PV)-expressing INs (PVIs) in the dentate gyrus carry large numbers of dendritic spines, which determine plastic changes in protein expression and which undergo input selective structural plasticity in response to behavioural challenge. We also showed that dendrite-targeting SOMIs in the dentate gyrus are crucial for spatial memory precision and the coordination of engram cells. Importantly, during this period we have developed a number of molecular tools for cell type- and circuit-specific interference with IN plasticity, which we will now apply to probe the functional impact of IN plasticity at the level of neuronal networks and behaving mice. Beyond this we will use immediate early gene imaging to investigate whether hippocampal INs themselves become part of a memory engram.

主细胞被视为大脑计算的处理单元。它们在活动模式中编码信息，并将此信息传达给其他本地或远程主细胞。此外，主细胞在突触传递和连接中表现出经验依赖性的功能和结构变化。这种可塑性使有机体能够适应新的情况并形成记忆。然而，主要的细胞活动在时间和空间上受到各种类型的抑制性GABA能中间神经元的严格调节。最近的一些研究，包括我们研究单位（RU）的一些研究，表明与长期以来的信念相反，中间神经元（IN）上的突触也会发生强烈的塑性变化。这是高度相关的，因为GABA能抑制细胞的连接或募集的变化可能对主细胞的时间和空间活动模式产生深远影响。在该研究单位的第一个资助期内，我们首次证明了齿状回中的核周靶向小清蛋白（PV）表达IN（PVIs）携带大量树突棘，这些树突棘决定蛋白质表达的可塑性变化，并在应对行为挑战时进行输入选择性结构可塑性。我们还发现，树突靶向的SOMIs在齿状回是至关重要的空间记忆精度和记忆印迹细胞的协调。重要的是，在此期间，我们已经开发了一些分子工具，用于细胞类型和电路特异性干扰IN可塑性，我们现在将应用这些工具来探测IN可塑性在神经元网络和行为小鼠水平上的功能影响。除此之外，我们将使用即时早期基因成像来研究海马IN本身是否成为记忆印迹的一部分。