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Curr Biol. 2016 Sep 12;26(17):2351-7. doi: 10.1016/j.cub.2016.06.056. Epub 2016 Sep 1.

Hippocampal Activation of Rac1 Regulates the Forgetting of Object Recognition Memory.

Author information

1
School of Life Sciences, Tsinghua University, Beijing 100084, China.
2
School of Life Sciences, Tsinghua University, Beijing 100084, China. Electronic address: zhongyi@tsinghua.edu.cn.

Abstract

Forgetting is a universal feature for most types of memories. The best-defined and extensively characterized behaviors that depict forgetting are natural memory decay and interference-based forgetting [1, 2]. Molecular mechanisms underlying the active forgetting remain to be determined for memories in vertebrates. Recent progress has begun to unravel such mechanisms underlying the active forgetting [3-11] that is induced through the behavior-dependent activation of intracellular signaling pathways. In Drosophila, training-induced activation of the small G protein Rac1 mediates natural memory decay and interference-based forgetting of aversive conditioning memory [3]. In mice, the activation of photoactivable-Rac1 in recently potentiated spines in a motor learning task erases the motor memory [12]. These lines of evidence prompted us to investigate a role for Rac1 in time-based natural memory decay and interference-based forgetting in mice. The inhibition of Rac1 activity in hippocampal neurons through targeted expression of a dominant-negative Rac1 form extended object recognition memory from less than 72 hr to over 72 hr, whereas Rac1 activation accelerated memory decay within 24 hr. Interference-induced forgetting of this memory was correlated with Rac1 activation and was completely blocked by inhibition of Rac1 activity. Electrophysiological recordings of long-term potentiation provided independent evidence that further supported a role for Rac1 activation in forgetting. Thus, Rac1-dependent forgetting is evolutionarily conserved from invertebrates to vertebrates.

KEYWORDS:

Rac1; active forgetting; hippocampus; memory decay; novel object recognition memory; retroactive interference

PMID:
27593377
DOI:
10.1016/j.cub.2016.06.056
[Indexed for MEDLINE]
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