Activation of G Signaling Enhances Memory Consolidation and Slows Cognitive Decline.

Publication Year
2018

Type

Journal Article
Abstract

<p>Perhaps the most devastating decline with age is the&nbsp;loss of memory. Therefore, identifying mechanisms to restore memory function with age is critical. Using C.&nbsp;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&nbsp;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.</p>

Journal
Neuron
Volume
98
Issue
3
Pages
562-574.e5
Date Published
2018 May 02
ISSN Number
1097-4199
Alternate Journal
Neuron
PMID
29656871