A new memory is stabilized through a process of consolidation, which is known to depend on a critical phase of protein synthesis. Consolidated memories are widely believed to be stable and resilient to disruption. This belief, however, has been recently challenged by studies showing that established memories become labile when reactivated and, furthermore, require another phase of protein synthesis to be maintained. Although this process has been termed """"""""re-consolidation"""""""", it is not known whether it is, in fact, a true recapitulation of consolidation. Very little is known about the underlying mechanisms and the specific functions of memory reconsolidation. This knowledge is not only essential for the understanding of how memory works, but it will also contribute to the development of novel strategies for treating psychiatric conditions based on traumatic memories (i.e. post-traumatic stress disorders, phobias and depression) and novel approaches for increasing memory strength. In this project, we propose to use a fear-conditioned-based task (inhibitory avoidance, IA) and molecular investigations to carry out a comparative multiple level analysis of the anatomical and temporal molecular requirements of memory consolidation and reconsolidation.
Our Aims are to determine to what extent both consolidation and reconsolidation involve the same molecules and brain areas (circuits) with similar temporal dynamics and to test the functional roles and the contribution of modulation on memory reconsolidation. The results of this project should provide important information for developing new strategies for the pharmacotherapeutic intervention of cognitive disorders caused by traumatic memories (i.e. PTSD, phobias, addiction and depression) and debilitating conditions of memory loss such as those occurring in aging and Alzheimer's Disease. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
1R01MH074736-01A2
Application #
7192796
Study Section
Neurobiology of Learning and Memory Study Section (LAM)
Program Officer
Osborn, Bettina D
Project Start
2007-01-01
Project End
2011-12-31
Budget Start
2007-01-01
Budget End
2007-12-31
Support Year
1
Fiscal Year
2007
Total Cost
$379,811
Indirect Cost
Name
Mount Sinai School of Medicine
Department
Physiology
Type
Schools of Medicine
DUNS #
078861598
City
New York
State
NY
Country
United States
Zip Code
10029
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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