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

项目摘要：在大脑中运行的多种记忆系统中，情节记忆由 记忆过去事件发生的地点和时间的能力，是一种最近发展、后来发展和 认知功能早期恶化。早期生活中的情景记忆很快就会被遗忘，这是一种众所周知的现象 婴儿健忘症发生在人类和非人类动物身上。海马体，一种进化上的 古老的、高度组织的皮质部分，对于空间位置和事件的关系绑定是必不可少的 转化为空间和心理轨迹以及记忆片段。序列数据的快速编码和合并 记忆事件的空间体验被认为是通过呈现这样的轨迹来实现的 在导航和睡眠/休息期间的时间压缩的海马区“放置细胞”序列中 在(即，预放，支持快速编码)之前和之后(即，重放，支持合并) 新奇的体验。海马体经历发育关键期和功能成熟 在大鼠出生后24天左右(P24)，啮齿动物的婴儿健忘症结束。我们的主要目标是 探索和理解记忆发育对海马区突触可塑性和 通过研究海马区整体位置细胞编码的发展，获得早期生命体验。我们 联合记录觉醒-行为和睡眠中的大量神经元的慢性电生理记录 在最近描述的三个发育阶段的大鼠出生后生活中，通过海马区注入 突触可塑性增强剂，在丰富的环境中养育或早期视觉剥夺(黑暗养育)， 以及用于解码空间轨迹的计算方法。圆满完成我们提出的目标 有望揭示大鼠的这种发育机制和因素，这将有助于理解 人类情节记忆的发展和出现，而这种侵入性的方法不是 有可能。我们的发现可能会更普遍地影响我们对发育中的神经精神脑的理解 自闭症、精神分裂症和智力残疾等疾病。

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.