(The) role of BAF chromatin remodeling complex in long-term fear memmory formation

Abstract

Epigenetic regulation of gene expression has been implicated in long-lasting memory formation. However, little is known about the role of chromatin remodeling mechanism in learning and memory. Recent study reports that BAF53b, a post-mitotic neuron-specific subunit of Brg/Brm-associated factor (BAF) chromatin remodeling complex is involved in hippocampus-dependent memory formation. However, whether BAF53b plays a role for long-term fear memory formation in lateral amygdala (LA), and its underlying mechanisms remain unknown. To address these issues, I used viral vectors to manipulate expression level of BAF53b specifically in LA and investigated its effects on long-term memory formation and synaptic structural plasticity using auditory fear conditioning paradigm. First, I found that Baf53b knockdown in LA neurons impaired long-term, but not short-term, fear memory formation, proving that BAF53b function in LA is essential for long-term fear memory formation. Second, transient BAF53b overexpression in LA enhanced long-term memory up to one month with no effect on short-term memory. Third, at the synapse level, confocal imaging of synaptic spines, visualized with GFP or dye injection in LA after fear learning revealed that the density of thin-type spine was specifically increased in BAF53b-overexpressing neurons one hr after learning, while head volume of mushroom-type spine in BAF53b knockdown neurons was significantly decreased compared to that in control neurons 24 hrs after learning. In parallel to this result, RT-PCR analysis showed that Baf53b knockdown blocked activity-dependent upregulation of miR132, which is known to be involved in regulation of activity-dependent spine enlargement. Taken together, my results demonstrate that BAF53b in LA is essential for long-term fear memory formation of auditory fear conditioning and reveal novel underlying mechanisms of BAF53b during long-lasting memory formation.