Deciphering dynamic and stable prefrontal representation of memory contents in mice

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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.