Deciphering dynamic and stable prefrontal representation of memory contents in mice

记忆功能是在跨越几个数量级的广泛时间范围内在大脑中实现的。在秒的时间尺度上，工作记忆(WM)允许保持与任务相关的信息活跃。相比之下，长期存储的记忆可以访问几个月或几年，在某些情况下可以访问整个一生。解决调节短期和长期记忆过程的神经机制对该领域提出了一个关键的挑战，并与我们理解以短期或长期记忆受损为特征的疾病状态(例如，分别是精神分裂症和阿尔茨海默病)有关。前额叶皮质(PFC)是大脑的短期和长期记忆的中央区域，因为它支持在几秒钟的时间尺度上的高度动态行为，以及在数周过程中以稳定的神经元表征的形式的长期记忆。然而，调节灵活招聘(例如在规则转换期间)和稳定表征(例如上下文表征)之间平衡的机制并不是很好，将在这项拟议的研究中进行审查。我们的目标特别是要问：(1)相同或不同的神经元集合是否参与了短时间和长时间尺度上的信息表示？(2)随着时间的推移，海马区对mPFC的输入如何塑造任务特异性活动？(3)在小鼠重复接受相同记忆任务的过程中，活跃的前额叶细胞作为代表WM任务在随后几天或几周内执行的整体的一部分，其稳定性有多大？在拟议的项目中，我们将使用多学科方法来解决这些悬而未决的问题，该方法包括单单元记录、单光子和双光子钙离子成像和行为分析。

Memory functions are realized in the brain over a broad range of time scales spanning several orders of magnitude. On the time scale of seconds, working memory (WM) allows to keep task-relevant information active. In contrast, memories stored for long-term can be accessed for months or for years, and in some cases for the entire lifetime. Resolving the neuronal mechanisms mediating short- and long-term memory processes poses a key challenge for the field and bears relevance for our understanding of disease states characterized by impaired short- or long-term memory (e.g. schizophrenia and Alzheimer’s disease, respectively). The prefrontal cortex (PFC) is a central brain region for short- and long-term memory as it supports highly dynamic behaviors on time scales of seconds as well as long-term memory in form of stable neuronal representations over the course of weeks. However, the mechanisms mediating a balance between flexible recruitment (e.g. during rule switching) and stable representation (e.g. context representation) are not well understood and will be examined in this proposed study. Particularly we aim to ask: (1) Do the same or different sets of neurons participate in the representation of information on short and long temporal scales? (2) How do hippocampal inputs to the mPFC shape task-specific activities over time? (3) How stable is the participation of an active prefrontal cell as part of the ensemble representing the execution of a WM task on subsequent days or weeks during repetitive exposure of mice to the same memory task? In the proposed project we will tackle these open questions using a multidisciplinary approach consisting of single unit recordings, 1- and 2-Photon Ca2+ imaging and behavioural analysis.