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: 8930188
• 负责人: Laura L Colgin
• 金额: $ 38.63万
• 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/8930188
• 关键词: Affect; Alzheimer' s Disease; Behavioral; Brain region; Cells; Code; Conflict (Psychology); Coupled; Couples; Data; Disease; Ensure; Environment; Exhibits; Foundations; Frequencies; Future; Goals; Health; 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; Work; entorhinal cortex; improved; memory encoding; memory process; memory retrieval; mouse model; object recognition; operation; prospective; 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（由申请人提供）：异常伽马节律见于阿尔茨海默病和精神分裂症，可能与这些疾病中的记忆障碍有关。因此，了解伽马节律在记忆中的作用是必要的。不同的快（~65 - 100 Hz）和慢（~25 - 55 Hz）伽马亚型将输入不同地路由到海马体，海马体是对记忆至关重要的大脑区域。快速伽马将海马体与来自内侧内嗅皮层（MEC）的当前感觉输入联系起来。慢伽马耦合海马子区CA1与CA3，一个子区的记忆检索必不可少的。尽管如此，慢伽马和快伽马与记忆处理的功能相关性在很大程度上仍然未知。拟议的工作将测试这一假设，即慢和快伽马在海马网络中执行不同的功能，快伽马促进记忆编码和慢伽马介导的记忆检索。这些研究将采用多位点电生理记录的局部场电位和单个单位活动在自由行为的啮齿动物。具体目标1将测试海马"位置细胞"和MEC "网格细胞"在慢和快伽马期间是否不同地编码位置，如预期的那样，如果慢和快伽马在功能上不同。将在线性轨道上跑步的大鼠中记录位置细胞和网格细胞的集合。轨道的一维性质将允许相同的轨迹进行比较，为慢和快伽马周期。贝叶斯解码技术将应用于破译缓慢和快速伽马相关轨迹的神经元整体活动。如果快速伽马涉及内存编码，则位置和网格单元应该在快速伽马期间编码最近的位置。如果慢伽马参与记忆检索，那么位置和网格单元代码应该预测在慢伽马期间即将到来的位置。具体目标2将使用空间记忆任务测试快速伽马是否促进记忆编码。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着减少是否与错误试验相关。此外，目标2将测试在编码期间对穿通路径的快速伽马刺激是否会改善阿尔茨海默病（AD）小鼠模型的记忆。将效应与缓慢伽马刺激进行比较，以确定快速伽马定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，以及在正确而非错误的试验中，慢伽马是否在记忆提取过程中选择性增强。该目的还将测试在记忆提取期间对Schaffer侧支的缓慢γ刺激是否改善AD小鼠的记忆。将效果与快速伽马刺激进行比较，以确定慢速伽马计时是否特别适合记忆检索。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。