Activation of G Signaling Enhances Memory Consolidation and Slows Cognitive Decline. Author Rachel Arey, Geneva Stein, Rachel Kaletsky, Amanda Kauffman, Coleen Murphy Publication Year 2018 Type Journal Article Abstract Perhaps the most devastating decline with age is the loss of memory. Therefore, identifying mechanisms to restore memory function with age is critical. Using C. elegans associative learning and memory assays, we identified a gain-of-function G signaling pathway mutant that forms a long-term (cAMP response element binding protein [CREB]-dependent) memory following one conditioned stimulus-unconditioned stimulus (CS-US) pairing, which usually requires seven CS-US pairings. Increased CREB activity in AIM interneurons reduces the threshold for memory consolidation through transcription of a set of previously identified "long-term memory" genes. Enhanced G signaling in the AWC sensory neuron is both necessary and sufficient for improved memory and increased AIM CREB activity, and activation of G specifically in aged animals rescues the ability to form memory. Activation of G in AWC sensory neurons non-cell autonomously induces consolidation after one CS-US pairing, enabling both cognitive function maintenance with age and restoration of memory function in animals with impaired memory performance without decreased longevity. Keywords Animals, Caenorhabditis elegans, Signal Transduction, Animals, Genetically Modified, Cognitive Dysfunction, Cyclic AMP Response Element-Binding Protein, GTP-Binding Protein alpha Subunits, Gq-G11, Memory Consolidation Journal Neuron Volume 98 Issue 3 Pages 562-574.e5 Date Published 2018 May 02 ISSN Number 1097-4199 DOI 10.1016/j.neuron.2018.03.039 Alternate Journal Neuron PMCID PMC5934306 PMID 29656871 PubMedPubMed CentralGoogle ScholarBibTeXEndNote X3 XML