Open AccessRNA interference in hippocampus demonstrates opposing roles for CREB and PP1α in contextual and temporal long‐term memory
Author(s) -
Peters M.,
Bletsch M.,
Catapano R.,
Zhang X.,
Tully T.,
Bourtchouladze R.
Publication year - 2009
Publication title -
genes, brain and behavior
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.315
H-Index - 91
eISSN - 1601-183X
pISSN - 1601-1848
DOI - 10.1111/j.1601-183x.2009.00474.x
Subject(s) - gene knockdown , creb , rna interference , hippocampus , neuroscience , small interfering rna , biology , synaptic plasticity , microbiology and biotechnology , long term potentiation , memory consolidation , long term memory , protein phosphatase 1 , phosphatase , psychology , gene , rna , genetics , phosphorylation , transcription factor , cognition , receptor
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.