Hippocampal Activation of Rac1 Regulates the Forgetting of Object Recognition Memory.
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.
School of Life Sciences, Tsinghua University, Beijing 100084, China.
Yunlong
Y
Liu
School of Life Sciences, Tsinghua University, Beijing 100084, China.
Shuwen
S
Du
School of Life Sciences, Tsinghua University, Beijing 100084, China.
Li
L
Lv
School of Life Sciences, Tsinghua University, Beijing 100084, China.
Bo
B
Lei
School of Life Sciences, Tsinghua University, Beijing 100084, China.
Wei
W
Shi
School of Life Sciences, Tsinghua University, Beijing 100084, China.
Yikai
Y
Tang
School of Life Sciences, Tsinghua University, Beijing 100084, China.
Lianzhang
L
Wang
School of Life Sciences, Tsinghua University, Beijing 100084, China. Electronic address: zhongyi@tsinghua.edu.cn.
Yi
Y
Zhong
D000818:Animals; D006624:Hippocampus / Q000502:physiology*; D017774:Long-Term Potentiation; D008297:Male; D008568:Memory; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000502:physiology; D009479:Neuropeptides / Q000235:genetics* / Q000378:metabolism; D021641:Recognition, Psychology; D014796:Visual Perception; D020830:rac1 GTP-Binding Protein / Q000235:genetics* / Q000378:metabolism
D009479:Neuropeptides; C484602:Rac1 protein, mouse; D020830:rac1 GTP-Binding Protein
Rac1; active forgetting; hippocampus; memory decay; novel object recognition memory; retroactive interference