Development and organization of brain-wide neuronal ensemble circuits underlying memory and decision making

项目总结/文摘

Project Summary/Abstract Episodic memory and memory-guided decision making are quintessential cognitive functions ensuring our identity, successful everyday life, and survival. Memories have a strong spatial and temporal sequential component. The field of memory research has long used rodent spatial navigation on linear environments as a framework for studying memory encoding and consolidation. Large-scale electrophysiological recordings from the adult rodent brain performed during animal navigation in novel environments have established that neuronal ensemble computations within and between the hippocampus and medial entorhinal cortex (MEC) are critical for the encoding and consolidation of spatial memories. During memory-guided decision- making tasks, the hippocampus and mPFC neurons re-engage in coordinated computations and communication, particularly during the successful trials. Optimal investigation of memory and decision-making processes require simultaneous interrogation of large ensembles of neurons from interconnected brain areas such as MEC and the hippocampus, and hippocampus and mPFC, respectively. Without exception, these experiments have been performed exclusively in adult animals where large neuronal samples could be obtained in freely-behaving rodents. Yet these findings in the adult brain raise new critical, still unanswered questions: When and how do coordinated activities between hippocampal neuronal ensembles and their upstream/downstream MEC emerge during postnatal life to support encoding and consolidation of long-term memories? When and how do mPFC neuronal ensemble patterns critical for decision making mature and how does their coordination with the hippocampus develop during postnatal life? In this proposal, I will investigate the age- and experience-dependent early- postnatal development of neuronal ensemble patterns known to be significant for spatial memory and navigation and decision making in the adult rat. The chronic, large-scale electrophysiological recordings will be performed over several days in freely-behaving and sleeping developing and adult rats simultaneously from interconnected brain areas, MEC and the hippocampus and the hippocampus and mPFC, respectively. These experiments will define the principles and stages of coordinated development across connected brain areas, their age and experience-dependence and the developmental critical periods specific to each brain area investigated.