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To understand how distinct memories are formed and stored in the brain is an important and fundamental question in neuroscience and computational biology. A population of neurons, termed engram cells, represents the physiological manifestation of a specific memory trace and is characterized by dynamic changes in gene expression, which in turn alters the synaptic connectivity and excitability of these cells. Recent applications of single-cell RNA sequencing (scRNA-seq) and single-nucleus RNA sequencing (snRNA-seq) are promising approaches for delineating the dynamic expression profiles in these subsets of neurons, and thus understanding memory-specific genes, their combinatorial patterns and regulatory networks. The aim of this article is to review and discuss the experimental and computational procedures of sc/snRNA-seq, new studies of molecular mechanisms of memory aided by sc/snRNA-seq in human brain diseases and related mouse models, and computational challenges in understanding the regulatory mechanisms underlying long-term memory formation. [ABSTRACT FROM AUTHOR] more...