Distinct mechanisms for memory storage and retrieval in hippocampal engram cells

NIH RePORTER · NIH · R21 · $423,823 · view on reporter.nih.gov ↗

Abstract

Abstract Neurobiological mechanisms underlying learning and memory have been extensively studied in animals. However, very little is known about the cellular processes that support retrieval. This may be the case because retrieval is often assumed to be a direct function of memory strength. The more learning that took place, the easier retrieval should be. However, research on human memory has demonstrated that storage strength and retrieval strength are dissociable processes. The former is long-lasting and influenced by the amount of training while the latter fluctuates and depends on temporal factors like how long ago the memory was encoded and retrieved. These unique properties suggest that storage strength and retrieval strength are regulated by distinct cellular mechanisms. Consistent with this idea, norepinephrine (NE) release is required for memory retrieval in the hippocampus but is not necessary for learning. Conversely, dopamine (DA) release is essential for learning but is not required for memory retrieval. Given that much is already known about DA and the role it plays in learning, the current application will characterize the relationship between NE release, intrinsic excitability and memory retrieval. In doing so, we will test the hypotheses that: 1) Phasic release of NE during testing enhances memory retrieval and prevents forgetting 2) Phasic release of NE increases the intrinsic excitability of engram cells and facilitates their reactivation during testing.

Key facts

NIH application ID
10235095
Project number
1R21NS122356-01
Recipient
UNIVERSITY OF CALIFORNIA AT DAVIS
Principal Investigator
Brian J Wiltgen
Activity code
R21
Funding institute
NIH
Fiscal year
2021
Award amount
$423,823
Award type
1
Project period
2021-04-01 → 2022-09-30