Our ability to encode the events that occur in our world, store that information, and then retrieve it at a later time is essential for survival. Our memory serves the essential capacity to integrate past events into current adaptive behavior. Thus, understanding brain processes involved in memory formation is of critical importance from a basic scientific perspective, as it can provide mechanistic insights into a fundamental aspect of cognitive behavior. The overarching goal of this research project is to elucidate brain mechanisms of memory by using a powerful model system, the marine mollusk Aplysia, to forge direct links between neuronal plasticity expressed at the cellular and molecular levels, and specific phases of enduring memory for sensitization expressed behaviorally. To accomplish this goal, there are three Specific Aims: A BEHAVIORAL ANALYSIS will be aimed at identifying the """"""""rules"""""""" that govern memory formation for a range of temporally discrete forms of memory for sensitization. Of special importance will be the unique roles of different patterns of training in the formation of mechanistically distinct forms of memory. A SYNAPTIC ANALYSIS will be aimed at establishing synaptic analogs of the different forms of memory revealed in the Behavioral Analysis, and determining the synaptic mechanisms that are recruited into play in forming these diverse memories. A MOLECULAR ANALYSIS will be aimed at identifying """"""""molecular profiles"""""""" for different forms of memory by examining the molecular cascades (the genes, messages and proteins) that are involved in altering synaptic strength during memory formation. Relevance to public health: The importance of understanding brain mechanisms underlying memory can be especially appreciated in cases where memory is impaired, such as in Alzheimer's Disease, Post-Traumatic Stress Disorders, and in victims of accidents or strokes. Thus a major challenge in mental health is to achieve a basic understanding of the brain mechanisms that are engaged in normal memory formation, and how those mechanisms are impaired when memory is compromised by disease or injury. Such an understanding is essential for developing effective therapies for cognitive problems involving memory impairment.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH041083-22
Application #
7813982
Study Section
Special Emphasis Panel (ZRG1-IFCN-B (03))
Program Officer
Osborn, Bettina D
Project Start
1986-03-01
Project End
2012-03-31
Budget Start
2010-04-01
Budget End
2011-03-31
Support Year
22
Fiscal Year
2010
Total Cost
$605,233
Indirect Cost
Name
University of California Irvine
Department
Other Basic Sciences
Type
Schools of Arts and Sciences
DUNS #
046705849
City
Irvine
State
CA
Country
United States
Zip Code
92697
Shobe, Justin; Philips, Gary T; Carew, Thomas J (2016) Transforming growth factor ? recruits persistent MAPK signaling to regulate long-term memory consolidation in Aplysia californica. Learn Mem 23:182-8
Mirisis, Anastasios A; Alexandrescu, Anamaria; Carew, Thomas J et al. (2016) The Contribution of Spatial and Temporal Molecular Networks in the Induction of Long-term Memory and Its Underlying Synaptic Plasticity. AIMS Neurosci 3:356-384
Stough, Shara; Kopec, Ashley M; Carew, Thomas J (2015) Synaptic generation of an intracellular retrograde signal requires activation of the tyrosine kinase and mitogen-activated protein kinase signaling cascades in Aplysia. Neurobiol Learn Mem 125:47-54
Kopec, Ashley M; Philips, Gary T; Carew, Thomas J (2015) Distinct Growth Factor Families Are Recruited in Unique Spatiotemporal Domains during Long-Term Memory Formation in Aplysia californica. Neuron 86:1228-39
Pu, Lu; Kopec, Ashley M; Boyle, Heather D et al. (2014) A novel cysteine-rich neurotrophic factor in Aplysia facilitates growth, MAPK activation, and long-term synaptic facilitation. Learn Mem 21:215-22
Fischbach, Soren; Kopec, Ashley M; Carew, Thomas J (2014) Activity-dependent inhibitory gating in molecular signaling cascades induces a novel form of intermediate-term synaptic facilitation in Aplysia californica. Learn Mem 21:199-204
Philips, Gary T; Ye, Xiaojing; Kopec, Ashley M et al. (2013) MAPK establishes a molecular context that defines effective training patterns for long-term memory formation. J Neurosci 33:7565-73
Kopec, Ashley M; Carew, Thomas J (2013) Growth factor signaling and memory formation: temporal and spatial integration of a molecular network. Learn Mem 20:531-9
Philips, Gary T; Kopec, Ashley M; Carew, Thomas J (2013) Pattern and predictability in memory formation: from molecular mechanisms to clinical relevance. Neurobiol Learn Mem 105:117-24
Ye, Xiaojing; Marina, Andreea; Carew, Thomas J (2012) Local synaptic integration of mitogen-activated protein kinase and protein kinase A signaling mediates intermediate-term synaptic facilitation in Aplysia. Proc Natl Acad Sci U S A 109:18162-7

Showing the most recent 10 out of 21 publications