BAF53b, an epigenetic factor involved in nucleosome remodeling, is induced in the lateral amygdala neurons after fear learning, and it regulates long-term memory consolidation.

How is a newly acquired memory transformed into a stable, long-lasting memory? This is a central question in understanding memory formation. The memory is stabilized by memory consolidation processes 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 in memory formation has been largely unexplored. The Korean research group led by Professor Jin-Hee Han of the Department of Biological Sciences of Korea Advanced Institute of Science and Technology (KAIST) showed that BAF53b, an epigenetic factor involved in nucleosome remodeling, is induced after fear learning, and it contributes to the permanent storage of the memory.

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 have shown that the functional loss of BAF53b results in a deficit of consolidation of hippocampus- and nucleus-accumbens-dependent memory in rodents. However, it was unclear whether BAF53b expression is regulated during memory formation and how BAF53b regulates fear memory in the amygdala, a key brain region for fear memory encoding and storage. To address these questions, Professor Han’s lab used viral vector approaches to either decrease or increase BAF53b function, specifically in the lateral amygdala (LA) of adult mice, and investigated their effects on memory formation using an auditory fear conditioning paradigm. Auditory fear conditioning is a behavioral paradigm that represents a fear response (freezing) to a neutral tone after a training session associates an aversive foot shock (unconditioned stimulus) with a neutral tone (conditioned stimulus). The results showed 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 auditory fear conditioning induced BAF53b 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. Together, these results provide 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. This suggests an idea of how nucleosome remodeling can be regulated during long-term memory formation and how it contributes to the permanent storage of associative fear memory in the lateral amygdala, which is relevant to fear and anxiety-related mental disorders.

This work was published in the Journal of Neuroscience in March 2017.

Contact Information:
Han, Jin-Hee (Dept. of Biological Sciences)