Understanding the roles of slow and fast gamma rhythms in memory processing

了解慢伽马节律和快伽马节律在记忆处理中的作用

• 批准号: 9432421
• 负责人: Laura L Colgin
• 金额: $ 10.6万
• 依托单位: UNIVERSITY OF TEXAS AT AUSTIN
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-25 至 2019-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9432421
• 关键词: Affect; Alzheimer' s Disease; Alzheimer' s disease model; Behavioral; Brain region; Cells; Code; Conflict (Psychology); Coupled; Couples; Data; Dimensions; Disease; Electrophysiology (science); Ensure; Environment; Exhibits; Foundations; Frequencies; Future; Goals; Hippocampus (Brain); Individual; Knowledge; Learning; Link; Location; Medial; Mediating; Memory; Memory impairment; Modeling; Mus; Nature; Neurons; Pattern; Perforant Pathway; Phase; Play; Protocols documentation; Rattus; Retrieval; Rodent; Role; Route; Running; Schizophrenia; Sensory; Signal Transduction; Techniques; Testing; Time; Training; Work; entorhinal cortex; improved; memory encoding; memory process; memory retrieval; mouse model; object recognition; operation; prospective; public health relevance; sensory input; spatial memory; theories

DESCRIPTION (provided by applicant): Aberrant gamma rhythms are seen in Alzheimer's disease and schizophrenia and may relate to memory impairments in these disorders. It is thus imperative to understand gamma rhythms role in memory. Separate fast (~65-100 Hz) and slow (~25-55 Hz) gamma subtypes differentially route inputs to hippocampus, a brain region critical for memory. Fast gamma links the hippocampus to current sensory inputs from the medial entorhinal cortex (MEC). Slow gamma couples hippocampal subfield CA1 with CA3, a subfield essential for memory retrieval. Still, the functional relevance of slow and fast gamma with regard to memory processing remains largely unknown. The proposed work will test the hypothesis that slow and fast gamma perform distinct functions in the hippocampal network, with fast gamma promoting memory encoding and slow gamma mediating memory retrieval. The studies will employ multisite electrophysiological recordings of local field potentials and single unit activityin freely behaving rodents. Specific Aim 1 will test whether hippocampal 'place cells' and MEC 'grid cells' code locations differently during slow and fast gamma, as expected if slow and fast gamma are functionally distinct. Ensembles of place cells and grid cells will be recorded in rats running on a linear track. The track's one-dimensional nature will allow identical trajectories to be compared for slow and fast gamma periods. Bayesian decoding techniques will be applied to decipher neuronal ensemble activity for slow and fast gamma-associated trajectories. If fast gamma is involved in memory encoding, then place and grid cells should encode recent locations during fast gamma. If slow gamma is involved in memory retrieval, then place and grid cell codes should predict upcoming locations during slow gamma. Specific Aim 2 will test whether fast gamma promotes memory encoding using spatial memory tasks. The proposed studies will determine whether fast gamma correlates with memory encoding and also whether significant decreases in fast gamma during memory encoding are associated with error trials. Furthermore, Aim 2 will test whether fast gamma stimulation of the perforant path during encoding will improve memory in a mouse model of Alzheimer's disease (AD). Effects will be compared to slow gamma stimulation to determine whether fast gamma timing in particular facilitates memory encoding. Specific Aim 3 will test whether slow gamma promotes memory retrieval in the same spatial memory tasks. The studies will determine whether slow gamma correlates with memory retrieval and whether slow gamma is selectively enhanced during memory retrieval in correct, but not error, trials. This Aim will also test whether slow gamma stimulation of the Schaffer collaterals during memory retrieval improves memory in AD mice. Effects will be compared to fast gamma stimulation to determine if slow gamma timing is particularly well suited for memory retrieval. Discovering functional differences between slow and fast gamma is expected to change the field's concept of gamma rhythms and thereby lay the foundation for exciting future discoveries.

描述(申请人提供)：异常伽马节律在阿尔茨海默病和精神分裂症中可见，可能与这些障碍中的记忆障碍有关。因此，了解伽马节律在记忆中的作用是非常必要的。不同的快(~65-100赫兹)和慢(~25-55赫兹)伽马亚型以不同的方式将输入传送到海马区，这是大脑中对记忆至关重要的区域。快速伽马将海马体与内侧嗅觉皮质(MEC)的当前感觉输入联系起来。慢伽马将海马区CA1和CA3结合在一起，CA3是记忆提取所必需的一个子区。尽管如此，慢伽马和快伽马在记忆处理方面的功能相关性在很大程度上仍不清楚。这项拟议的工作将检验这一假设，即慢伽马和快伽马在海马体网络中执行不同的功能，快速伽马促进记忆编码，慢伽马介导记忆提取。这项研究将采用多点电生理记录自由行为的啮齿动物的局部场电位和单个单位的活动。如果慢伽马和快伽马的功能不同，特定的目标1将测试在慢伽马和快伽马的过程中，海马体的“定位细胞”和MEC的“网格细胞”编码位置是否不同。在直线轨道上运行的大鼠身上，将记录到位置细胞和网格细胞的集合。该轨道的一维性质将允许比较慢伽马周期和快伽马周期的相同轨迹。贝叶斯解码技术将被应用于破译慢速和快速伽马相关轨迹的神经系综活动。如果内存编码涉及快速伽马，则位置和网格单元应在快速伽马期间对最近的位置进行编码。如果记忆检索涉及慢伽马，那么位置和网格单元代码应该在慢伽马期间预测即将到来的位置。《特定目标2》将测试快速伽马是否通过空间记忆任务促进记忆编码。这项拟议的研究将确定快速伽马是否与记忆编码相关，以及记忆编码期间快速伽马的显著下降是否与错误试验有关。此外，Aim 2将测试编码过程中快速伽马刺激穿透通路是否会改善阿尔茨海默病(AD)小鼠模型的记忆。效果将与慢伽马刺激进行比较，以确定快速伽马计时是否特别有利于记忆编码。具体目标3将测试在相同的空间记忆任务中，慢伽马是否能促进记忆提取。这些研究将确定慢伽马是否与记忆提取相关，以及在正确但不是错误的试验中，慢伽马是否在记忆提取过程中被选择性地增强。这一目标还将测试记忆恢复过程中对Schaffer侧支的缓慢伽马刺激是否会改善AD小鼠的记忆。我们将把效果与快速伽马刺激进行比较，以确定慢伽马计时是否特别适合记忆恢复。发现慢伽马和快伽马之间的功能差异有望改变该领域对伽马节律的概念，从而为令人兴奋的未来发现奠定基础。