Dynamic modulation of postnatal development of preconfigured and plastic time-compressed sequences

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Project summary: Of the multiple memory systems operating in the brain, episodic memory, defined by the ability to remember where and when events occurred in the past, is a recently evolved, later developing and early deteriorating cognitive function. Early-life episodic memories are rapidly forgotten, a phenomenon known as infantile amnesia occurring in humans and non-human animals. The hippocampus, an evolutionarily ancient, highly organized part of the cortex, is essential for the relational binding of spatial locations and events into spatial and mental trajectories and memory episodes. The rapid encoding and consolidation of sequential spatial experiences into memory episodes is believed to be achieved by the representation of such trajectories within time-compressed hippocampal ‘place cell’ sequences during navigation and the sleep/rest periods preceding (i.e., preplay, supporting rapid encoding) and following (i.e., replay, supporting consolidation) the novel experiences. The hippocampus undergoes a developmental critical period and functionally matures around postnatal day 24 (P24) in the rat, an age when infantile amnesia ends in rodents. Our main goal is to explore and understand the dependence of memory development on intrahippocampal synaptic plasticity and early-life experience by studying the development of ensemble place cell coding in the hippocampus. We combine chronic electrophysiologic recording of large ensembles of neurons in awake-behaving and sleeping rats across three recently described developmental stages in postnatal life with intra-hippocampal infusion of enhancers of synaptic plasticity, rearing in enriched environments or early-life visual deprivation (dark rearing), and computational methods for decoding spatial trajectories. The successful completion of our proposed aims promises to uncover such developmental mechanism and factors in the rat, which should help understand the development and emergence of episodic memories in the human, where such invasive approaches are not possible. Our findings could more generally impact our understanding of developmental neuro-psychiatric brain diseases like autism, schizophrenia, and intellectual disabilities.