Identifying a chromatin remodeling factor promoting long-lasting memory formation
How newly acquired memories are converted to stable, long-lasting memories is a central scientific question. A research team in the Department of Biological Sciences at KAIST has recently unveiled that BAF53b, an epigenetic factor involved in nucleosome remodeling, is induced in the lateral amygdala neurons after fear learning and promotes long-term memory consolidation.
A key function of the brain is to store information acquired from daily experiences. In many brain diseases such as Alzheimer’s disease, memory function is severely impaired. Memory is thought to be stabilized by the neural processes called consolidation that require new gene expression. Recently, neuroscientists have been focusing on epigenetic mechanisms that permanently change gene expression to study mechanisms of memory formation that last for a lifetime. However, among the epigenetic mechanisms, the role of ATP-dependent nucleosome remodeling factor has been largely unknown. A research group led by professor Jin-Hee Han at the Department of Biological Sciences from KAIST shows that BAF53b, an epigenetic factor involved in nucleosome remodeling, is induced after fear learning and promotes long-term memory consolidation.
BAF53b is a neuron-specific subunit of Brg/Brm-associated factor (BAF) complex, the ATP-dependent nucleosome remodeling complex. It is involved in activity-dependent dendritic outgrowth which is important for long-term memory formation. Recent studies show that the functional loss of BAF53b results in the deficit of consolidation of hippocampus and nucleus accumbens-dependent memory in rodents. Whether BAF53b is regulated during memory formation and how BAF53b regulates fear memory in the amygdala, a key brain region for fear memory encoding and storage, has remained unclear to researchers.
To address these questions, the KAIST research team used viral vector approaches to either decrease or increase BAF53b function specifically in the amygdala of adult mice and investigated their effects on fear memory formation. They demonstrated that a decrease in BAF53b disrupted long-term memory formation without affecting short-term memory, basal synaptic transmission and spine structures. The team also observed that BAF53b expression is increased at the late phase of consolidation. Moreover, transient BAF53b increase led to persistently enhanced memory formation, which was accompanied by an increase in thin-type spine density.
Taken together, these results provide the evidence that BAF53b is induced after learning, and that an increase in BAF53b level facilitates memory consolidation likely by regulating learning-related spine structural plasticity. These findings suggest an idea of how nucleosome remodeling can be regulated during long-term memory formation and contributes to the scientific understanding of the permanent storage of fear memory in the amygdala, which is relevant to fear and anxiety-related mental disorders.
Published in The Journal of Neuroscience, 29, Mar. 2018,
* lab webpage : https://sites.google.com/site/neuralcircuitandbehaviorlab