Learning and Memory Suppressors

背景：学习和记忆的神经生物学是一个重要的研究领域。学习和记忆是信息被编码、存储和从神经系统中检索的基本过程。几十年来对神经科学这一复杂领域的研究揭示了生物体正常学习和记忆所需的数百个基因。然而，令人惊讶的是，硬币的另一面，那些相反地作用于限制学习和记忆过程的基因，却没有那么为人所知和研究。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贡献新的见解。这方面的一个例子是相对较新的遗忘研究领域的出现，该领域源于对果蝇的开创性研究(最近已扩展到啮齿动物模型)。这项工作正在导致我们看待遗忘的方式的观念转变，从被动的记忆衰退过程转变为主动的记忆移除过程。此外，最近发现的多个记忆抑制基因表明，有一种重要的生物学需要来限制记忆过程，但为什么会这样还不清楚。因此，我的实验室的长期目标是(1)识别抑制记忆过程的新基因和各种细胞途径，以及(2)使用功能强大且适应性强的果蝇模型生物体，研究为什么需要这样的认知限制。最近的进展和目的：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，这些基因已知在基本细胞分泌途径的部分功能中发挥作用。在接下来的5年里，我和我的受训者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发挥作用来抑制记忆过程。我们将通过三个研究目标来实现这一点：(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仍处于初级阶段的研究领域，可以导致对学习和记忆的神经生物学的基本见解。我预计这项研究将发现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，推动加拿大对记忆遗传抑制的研究。

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.