Maintaining healthy cognitive functions, of which memory is a most important one, is one of the major goals of mental health research. Aging, diseases, stress and injury can lead to cognitive and memory impairments. It is estimated that up to one third of adults will experience a gradual decline in cognitive function known as mild cognitive impairment as they age. Furthermore, risk for Alzheimer's disease, memory loss and dementia increases with increasing age. Thus, minimizing or preventing cognitive and memory loss is very important as the average life span continues to lengthen. It is therefore imperative to understand the physiology of memory formation, persistence and storage and identify molecular mechanisms and targets that are associated with memory impairments in order to develop strategies that will prevent or reverse them. Newly learned information is in a labile state for a limited time and becomes a long-term memory through a process of stabilization that is known as memory consolidation. Once stable, memory can become labile again if retrieved and re-stabilizes through another process known as memory reconsolidation. Using contextual fear conditioning types of memory in rats, we have recently found that the growth factor insulin like growth factor II (IGF-II) acts as a potent memory enhancer when administered during the consolidation or reconsolidation phases. Furthermore, using inhibitory avoidance (IA), we have found that retrieval-dependent reconsolidation promotes memory strengthening and prevents forgetting. These findings suggest that it is possible to identify post-retrieval mechanisms that can be used as targets to develop new therapies that promote cognition and alleviate age-related memory decline. Using IA and social transmission of food preference in rats, this proposal will test the molecular mechanisms and brain circuitry of the retrieval-dependent IGF-II-induced memory enhancement. It will investigate circuitry and molecular mechanisms of retrieval-induced memory strengthening and prevention of forgetting. Finally, it will investigate how memory retrieval and IGF-II can be used in aging to delay or reverse memory impairments. Results from these studies will advance our knowledge of neural mechanisms underlying memory enhancement and aging-related cognitive impairment in rats.

Public Health Relevance

Capitalizing on recent findings from our ongoing project using the rat as an animal model, this project continuation aims at identifying the mechanisms and circuitry of memory enhancement in adult animals and in preventing or rescuing memory decay. The results of these studies may lead to the identification of new therapies that prevent or reverse memory impairments. Preventing or rescuing cognitive and memory loss is a most important goal in mental health research.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
4R01MH074736-10
Application #
8979718
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Buhring, Bettina D
Project Start
2005-07-01
Project End
2017-11-30
Budget Start
2015-12-01
Budget End
2017-11-30
Support Year
10
Fiscal Year
2016
Total Cost
Indirect Cost
Name
New York University
Department
Neurology
Type
Schools of Arts and Sciences
DUNS #
041968306
City
New York
State
NY
Country
United States
Zip Code
10012
Ye, Xiaojing; Kapeller-Libermann, Dana; Travaglia, Alessio et al. (2017) Direct dorsal hippocampal-prelimbic cortex connections strengthen fear memories. Nat Neurosci 20:52-61
Alberini, Cristina M; Travaglia, Alessio (2017) Infantile Amnesia: A Critical Period of Learning to Learn and Remember. J Neurosci 37:5783-5795
Katzman, Aaron; Alberini, Cristina M (2017) NLGN1 and NLGN2 in the prefrontal cortex: their role in memory consolidation and strengthening. Curr Opin Neurobiol 48:122-130
Steinmetz, Adam B; Johnson, Sarah A; Iannitelli, Dylan E et al. (2016) Insulin-like growth factor 2 rescues aging-related memory loss in rats. Neurobiol Aging 44:9-21
Travaglia, Alessio; Bisaz, Reto; Cruz, Emmanuel et al. (2016) Developmental changes in plasticity, synaptic, glia and connectivity protein levels in rat dorsal hippocampus. Neurobiol Learn Mem 135:125-138
Travaglia, Alessio; Bisaz, Reto; Sweet, Eric S et al. (2016) Infantile amnesia reflects a developmental critical period for hippocampal learning. Nat Neurosci 19:1225-33
Finsterwald, Charles; Steinmetz, Adam B; Travaglia, Alessio et al. (2015) From Memory Impairment to Posttraumatic Stress Disorder-Like Phenotypes: The Critical Role of an Unpredictable Second Traumatic Experience. J Neurosci 35:15903-15
Stern, Sarah A; Kohtz, Amy S; Pollonini, Gabriella et al. (2014) Enhancement of memories by systemic administration of insulin-like growth factor II. Neuropsychopharmacology 39:2179-90
Finsterwald, Charles; Alberini, Cristina M (2014) Stress and glucocorticoid receptor-dependent mechanisms in long-term memory: from adaptive responses to psychopathologies. Neurobiol Learn Mem 112:17-29
Bisaz, Reto; Travaglia, Alessio; Alberini, Cristina M (2014) The neurobiological bases of memory formation: from physiological conditions to psychopathology. Psychopathology 47:347-56

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