Learning and Memory Suppressors

学习和记忆抑制剂

• 批准号: RGPIN-2020-04009
• 负责人: Phan, Anna
• 金额: $ 2.7万
• 依托单位: University of Alberta
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2020
• 资助国家: 加拿大
• 起止时间: 2020-01-01 至 2021-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=716071
• 关键词: Learning; Memory; Suppressors

Background: The neurobiology of learning and memory is an area of significant research interest. Learning and memory is the fundamental process through which information is encoded, stored, and retrieved from the nervous system. Decades of research into this complex area of neuroscience have revealed hundreds of genes that are required for an organism to learn and remember normally. However, the other side of the coin, the genes that work in opposition to constrain learning and memory processes, are surprisingly less well known and studied. These genes are referred to as memory suppressor genes'. The study of these memory suppressor genes will undoubtedly contribute new insights into the neurobiology of memory. One example of this is the emergence of the relatively new field of forgetting research, which arose from groundbreaking work in fruit flies (and has recently been extended to rodent models). This work is leading to a conceptual shift in the way we view forgetting, from a passive process of memory decay to an active process of memory removal. Furthermore, the recent identification of multiple memory suppressor genes suggests there is an important biological need to limit memory processes, but why this is the case remains unclear. Thus, the long-term goals of my lab are (1) to identify novel genes and various cellular pathways that act to suppress memory processes, and (2) to investigate why there is a need for such cognitive constraints, using the powerful and adaptable fruit fly model organism. Recent Progress and Objectives: My recent work in this area has led to the identification of 3 highly conserved, novel memory suppressor genes that are known to function in parts of the fundamental cellular secretory pathway. Over the next 5 years, my trainees and I will use multilevel approaches and state-of-the-art techniques to investigate how these genes function to suppress memory processes. We will do this by pursuing 3 research objectives: (i) determine what aspects of memory are limited by these genes, (ii) identify how these genes alter neuron function to affect memory, and (iii) elucidate the cellular mechanisms of how these genes function to suppress memory. Impact: Our highly innovative approach integrates the study of basic cellular and neurobiological systems with the complex processes of memory. The identification of novel memory suppressor genes and their mechanisms of action is an area of research that is still in its infancy that can lead to fundamental insights into the neurobiology of learning and memory. I anticipate this research will uncover new and surprising roles for the cellular secretory pathway in limiting memory processes, advancing research into the genetic suppression of memory in Canada.

背景：学习和记忆的神经生物学是一个重要的研究领域。学习和记忆是神经系统编码、存储和检索信息的基本过程。几十年来对神经科学这一复杂领域的研究已经揭示了生物体正常学习和记忆所需的数百个基因。然而，硬币的另一面，与限制学习和记忆过程相反的基因，令人惊讶的是，人们对它的了解和研究较少。这些基因被称为记忆抑制基因。 对这些记忆抑制基因的研究无疑将为记忆的神经生物学研究提供新的视角。其中一个例子是相对较新的遗忘研究领域的出现，它起源于果蝇的开创性工作（最近已扩展到啮齿动物模型）。这项工作导致我们看待遗忘的方式发生了概念上的转变，从记忆衰退的被动过程转变为记忆消除的主动过程。此外，最近对多个记忆抑制基因的鉴定表明，限制记忆过程是一种重要的生物学需要，但为什么会这样仍然不清楚。因此，我的实验室的长期目标是（1）确定抑制记忆过程的新基因和各种细胞通路，以及（2）使用强大且适应性强的果蝇模式生物来研究为什么需要这种认知限制。 近期进展和目标：我最近在这一领域的工作导致了3个高度保守的，新的记忆抑制基因的鉴定，已知这些基因在基本细胞分泌途径的部分功能。在接下来的5年里，我和我的学员将使用多层次的方法和最先进的技术来研究这些基因如何抑制记忆过程。我们将通过追求3个研究目标来做到这一点：（i）确定记忆的哪些方面受到这些基因的限制，（ii）确定这些基因如何改变神经元功能以影响记忆，以及（iii）阐明这些基因如何发挥作用以抑制记忆的细胞机制。 影响：我们高度创新的方法将基本细胞和神经生物学系统的研究与复杂的记忆过程相结合。识别新的记忆抑制基因及其作用机制是一个研究领域，仍处于起步阶段，可以导致学习和记忆的神经生物学的基本见解。我预计这项研究将揭示细胞分泌途径在限制记忆过程中的新的和令人惊讶的作用，推进对加拿大记忆遗传抑制的研究。