title: Mechanisms of hippocampal long-term depression are required for memory enhancement by novelty exploration.
abstract: It is well known that novel environments can enhance learning and memory. However, the underlying mechanisms remain poorly understood. Here, we report that, in freely moving rats, novelty exploration facilitates the production of hippocampal CA1 long-term depression (LTD), a well characterized form of synaptic plasticity believed to be a cellular substrate of spatial learning, and thereby converts short-term memory (STM) into long-term memory (LTM) in an inhibitory avoidance learning procedure. Blocking the induction or the expression of CA1 LTD with two mechanistically and structurally distinct inhibitors prevents not only novelty acquisition but also the novelty exploration-promoted conversion of STM into LTM. Moreover, production of LTD with a strong electrical stimulation induction protocol or facilitation of hippocampal LTD by pharmacological inhibition of glutamate transporter activity mimics the behavioral effects of novelty exploration, sufficiently promoting the conversion of STM into LTM. Together, our findings suggest that induction of LTD may play an essential role not only in novelty acquisition but also in novelty-mediated memory enhancement.
authors.affiliation: Ministry of Education Key Laboratory of Child Development and Disorders, Children's Hospital of Chongqing Medical University, Chongqing 400014, People's Republic of China. zhifang.dong@gmail.com
authors.forename: Zhifang
authors.initials: Z
authors.lastname: Dong
authors.forename: Bo
authors.initials: B
authors.lastname: Gong
authors.forename: Hongjie
authors.initials: H
authors.lastname: Li
authors.forename: Yanrui
authors.initials: Y
authors.lastname: Bai
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Wu
authors.forename: Yan
authors.initials: Y
authors.lastname: Huang
authors.forename: Wenting
authors.initials: W
authors.lastname: He
authors.forename: Tingyu
authors.initials: T
authors.lastname: Li
authors.forename: Yu Tian
authors.initials: YT
authors.lastname: Wang
mesh_terms: D000818:Animals; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D005106:Exploratory Behavior / Q000502:physiology*; D006624:Hippocampus / Q000502:physiology*; D036881:Long-Term Synaptic Depression / Q000502:physiology*; D008297:Male; D008568:Memory / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley