Newly acquired information becomes a long-lasting memory through a process known as memory consolidation, which depends upon gene transcription and translation. The overall goal of this project is to elucidate the nature of the molecular pathways underlying memory consolidation using inhibitory avoidance (IA) as a memory task in rats. Previously, the PI's laboratory has discovered and characterized the fundamental role of the transcription factors CCAAT enhancer binding protein (C/EBP) beta and delta in the hippocampus during IA memory consolidation. The recent identification of some of the downstream genes regulated following the induction of C/EBP during memory consolidation together with other preliminary studies ongoing in the PI's laboratory led to the proposal of a novel, integrated working hypothesis for why these transcription factors have been evolutionarily selected to mediate long-term memory formation. To test this hypothesis, 3 specific Aims will be addressed:
AIM 1) To determine whether the role of C/EBPs in the hippocampus during memory consolidation is recruited through the activation of survival pathways in response to adaptive stress.
AIM 2) To determine whether the activation of survival pathways induces an autoregulation of the CREB- C/EBP pathway in the hippocampus during memory consolidation.
AIM 3) To determine whether C/EBPb and/or C/EBPd are directly involved in the regulation of the expression of genes, such as the tyrosine kinase receptor MuSK, that are believed to mediate synapse formation and/or survival (maintenance) in the adult brain. The understanding of how stress and survival pathways mediate memory formation will likely provide key information for developing novel strategies for the treatments of several pathologies, including cognitive and memory formation disorders, neurodegeneration and affective disorders.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
7R01MH065635-11
Application #
8448812
Study Section
Neurobiology of Learning and Memory Study Section (LAM)
Program Officer
Beckel-Mitchener, Andrea C
Project Start
2002-07-01
Project End
2012-12-03
Budget Start
2012-04-05
Budget End
2012-12-03
Support Year
11
Fiscal Year
2011
Total Cost
$461,610
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
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Ye, Xiaojing; Kohtz, Amy; Pollonini, Gabriella et al. (2015) Insulin Like Growth Factor 2 Expression in the Rat Brain Both in Basal Condition and following Learning Predominantly Derives from the Maternal Allele. PLoS One 10:e0141078
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Pascual-Lucas, Maria; Viana da Silva, Silvia; Di Scala, Marianna et al. (2014) Insulin-like growth factor 2 reverses memory and synaptic deficits in APP transgenic mice. EMBO Mol Med 6:1246-62
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Bisaz, Reto; Travaglia, Alessio; Alberini, Cristina M (2014) The neurobiological bases of memory formation: from physiological conditions to psychopathology. Psychopathology 47:347-56
Stern, Sarah A; Chen, Dillon Y; Alberini, Cristina M (2014) The effect of insulin and insulin-like growth factors on hippocampus- and amygdala-dependent long-term memory formation. Learn Mem 21:556-63
Bambah-Mukku, Dhananjay; Travaglia, Alessio; Chen, Dillon Y et al. (2014) A positive autoregulatory BDNF feedback loop via C/EBPβ mediates hippocampal memory consolidation. J Neurosci 34:12547-59
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
Stern, Sarah A; Alberini, Cristina M (2013) Mechanisms of memory enhancement. Wiley Interdiscip Rev Syst Biol Med 5:37-53

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