Neural mechanism of long-term memory storage and modulation

Memory is a way for people to acquire information through personal experiences and from media such as books, TV, and the internet. Relying on memory and the ability to gain new ones, the human brain is capable of adapting to survive in the ever-changing environment and can create marvels and build objects out of nature. Therefore, it is memory that creates modern civilization. Memory consists of synapses and neural ensembles in the brain which integrate multisensory information both spatially and temporally. Thus, memory bridges the link between cognitive domain information and physical domain neural connections, making them easier to track and study. Memory is the foundation of the brain's cognitive functions. Consequently, research into how the brain stores and retrieves memories reveals not only how the brain works to generate intelligence, but also suggests possible avenues for creating efficient machine learning algorithms that have evolved over millions of years. Recent breakthroughs in biotechnology have led to discoveries about the mechanisms underlying memory formation and retrieval, providing insight into neural memories at the cellular and synaptic levels as well as understanding neural coding for circuitry integration and operation. Particularly, the discovery of cellular memory engrams in the neocortex has revealed a highly parallel arrangement of memory circuits, which are located in layer ll of widely distributed cortical areas, including sensory cortices, primary visual cortices, and retrosplenial cortices. In this review, we summarize the most recent findings on memory engrams in the hippocampus and neocortex. We highlight the correlation between neural oscillations and cortical engram activities during memory formation. We also explore the evidence that long-range synchrony of theta-coupled gamma oscillations plays a key role in modulating cortical engram activity to create a brain-wide memory network. We explain how memory engrams in the neocortex are integrated and organized by indexing signals from the hippocampus, allowing memories to be registered allocated and retrieved in the brain. Lastly, we shed light on the molecular mechanisms especially epigenetic regulators involved in the physical regulation of memory persistency and flexibility. Deficiencies in the epigenetic regulation of these engrams may lead to memory deficits in various brain diseases. Additionally, the laminar-specific distribution of memory engrams in local cortical columns and the global organization of memory traces in distinct functional cortical regions may inspire the development of novel computing algorithms in machine learning to achieve brain-level intelligence. Taken together, the advances in methodology are paving the way for us to directly investigate the neural mechanisms of memory storage and retrieval in mammalian brain, giving insight into human cognition and inspiring new approaches in machine learning.