Laboratory of Spatial Memory, Nencki Institute of Experimental Biology, Polish Academy of Sciences, Pasteura 3, 02-093, Warsaw, Poland.
Mol Brain. 2021 Dec 4;14(1):172. doi: 10.1186/s13041-021-00880-w.
The ability to form, retrieve and update autobiographical memories is one of the most fascinating features of human behavior. Spatial memory, the ability to remember the layout of the external environment and to navigate within its boundaries, is closely related to the autobiographical memory domain. It is served by an overlapping brain circuit, centered around the hippocampus (HPC) where the cognitive map index is stored. Apart from the hippocampus, several cortical structures participate in this process. Their relative contribution is a subject of intense research in both humans and animal models. One of the most widely studied regions is the retrosplenial cortex (RSC), an area in the parietal lobe densely interconnected with the hippocampal formation. Several methodological approaches have been established over decades in order to investigate the cortical aspects of memory. One of the most successful techniques is based on the analysis of brain expression patterns of the immediate early genes (IEGs). The common feature of this diverse group of genes is fast upregulation of their mRNA translation upon physiologically relevant stimulus. In the central nervous system they are rapidly triggered by neuronal activity and plasticity during learning. There is a widely accepted consensus that their expression level corresponds to the engagement of individual neurons in the formation of memory trace. Imaging of the IEGs might therefore provide a picture of an emerging memory engram. In this review we present the overview of IEG mapping studies of retrosplenial cortex in rodent models. We begin with classical techniques, immunohistochemical detection of protein and fluorescent in situ hybridization of mRNA. We then proceed to advanced methods where fluorescent genetically encoded IEG reporters are chronically followed in vivo during memory formation. We end with a combination of genetic IEG labelling and optogenetic approach, where the activity of the entire engram is manipulated. We finally present a hypothesis that attempts to unify our current state of knowledge about the function of RSC.
形成、检索和更新自传体记忆的能力是人类行为最迷人的特征之一。空间记忆是记住外部环境布局并在其边界内导航的能力,它与自传体记忆领域密切相关。它由一个重叠的大脑回路提供服务,该回路以海马体(HPC)为中心,认知地图索引存储在其中。除了海马体,几个皮质结构也参与了这个过程。它们的相对贡献是人类和动物模型中研究的热点。研究最多的区域之一是后顶叶皮层(RSC),这是顶叶中与海马体结构紧密相连的一个区域。几十年来,已经建立了几种方法来研究记忆的皮质方面。其中最成功的技术之一是基于对即时早期基因(IEG)的大脑表达模式的分析。这群基因的共同特征是在生理相关刺激下,其 mRNA 翻译迅速上调。在中枢神经系统中,它们是由学习过程中的神经元活动和可塑性迅速触发的。人们普遍认为,它们的表达水平与单个神经元在记忆痕迹形成中的参与程度相对应。因此,IEG 的成像可能提供了记忆痕迹形成的图片。在这篇综述中,我们介绍了啮齿动物模型中后顶叶皮层 IEG 映射研究的概述。我们首先介绍经典技术,即蛋白质免疫组织化学检测和 mRNA 的荧光原位杂交。然后,我们介绍了先进的方法,即在记忆形成过程中,慢性地对体内荧光遗传编码的 IEG 报告基因进行跟踪。最后,我们结合了遗传 IEG 标记和光遗传学方法,对整个记忆痕迹的活动进行了操纵。我们最后提出了一个假设,试图将我们目前对 RSC 功能的认识统一起来。