Class IIa HDACs regulate learning and memory through dynamic experience-dependent repression of transcription

Yongchuan Zhu, Min Huang, Eric Bushong, Sebastien Phan, Marco Uytiepo, Elizabeth Beutter, Daniel Boemer, Kristin Tsui, Mark Ellisman and Anton Maximov ()
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Yongchuan Zhu: The Scripps Research Institute
Min Huang: The Scripps Research Institute
Eric Bushong: University of California
Sebastien Phan: University of California
Marco Uytiepo: The Scripps Research Institute
Elizabeth Beutter: The Scripps Research Institute
Daniel Boemer: The Scripps Research Institute
Kristin Tsui: The Scripps Research Institute
Mark Ellisman: University of California
Anton Maximov: The Scripps Research Institute

Nature Communications, 2019, vol. 10, issue 1, 1-14

Abstract: Abstract The formation of new memories requires transcription. However, the mechanisms that limit signaling of relevant gene programs in space and time for precision of information coding remain poorly understood. We found that, during learning, the cellular patterns of expression of early response genes (ERGs) are regulated by class IIa HDACs 4 and 5, transcriptional repressors that transiently enter neuronal nuclei from cytoplasm after sensory input. Mice lacking these repressors in the forebrain have abnormally broad experience-dependent expression of ERGs, altered synaptic architecture and function, elevated anxiety, and severely impaired memory. By acutely manipulating the nuclear activity of class IIa HDACs in behaving animals using a chemical-genetic technique, we further demonstrate that rapid induction of transcriptional programs is critical for memory acquisition but these programs may become dispensable when a stable memory is formed. These results provide new insights into the molecular basis of memory storage.

Date: 2019
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DOI: 10.1038/s41467-019-11409-0

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