RNA interference in hippocampus demonstrates opposing roles for CREB and PP1α in contextual and temporal long‐term memory
Year: 2009
Type: article
Abstract: 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.
Source: Genes Brain & Behavior
Institutions: Dart NeuroScience (United States), Celgene (United States)
Language: English
Topic: Memory and Neural Mechanisms
Subfield: Cognitive Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: bronze
OpenAlex ID: W2045264711