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Publication : RNA interference in hippocampus demonstrates opposing roles for CREB and PP1alpha in contextual and temporal long-term memory.

First Author  Peters M Year  2009
Journal  Genes Brain Behav Volume  8
Issue  3 Pages  320-9
PubMed ID  19191880 Mgi Jnum  J:151127
Mgi Id  MGI:4352809 Doi  10.1111/j.1601-183X.2009.00474.x
Citation  Peters M, et al. (2009) RNA interference in hippocampus demonstrates opposing roles for CREB and PP1alpha in contextual and temporal long-term memory. Genes Brain Behav 8(3):320-9
abstractText  We injected small interfering RNAs (siRNAs) directly into the hippocampus of wild-type mice, knocking down expression of cyclic AMP responsive element-binding protein (CREB) and disrupting long-term, but not short-term, memory after both contextual and trace fear conditioning. In contrast, similar knockdown of siRNA for protein phosphatase 1 (PP1) was sufficient to enhance contextual and temporal memory formation, thereby demonstrating with such a gain-of-function effect a lack of any general deleterious effect for this method of RNAi-mediated gene knockdown. Our findings clearly confirm that contextual memory formation involves CREB and PP1 as positive and negative regulators, respectively, and show for the first time that temporal memory formation shares this mechanism. More generally, we establish that direct injection of siRNA into identified adult brain regions yields specific gene knockdowns, which can be used to validate in vivo candidate genes involved in behavioral plasticity.
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