Stress contributes to myriad psychopathologies, including anxiety, depression, schizophrenia, and drug use relapse. A common thread binding these disorders appears to be the stress-associated alteration in cognitive processes, namely learning and memory. Considerable human and animal research has shown that the hippocampus, a brain structure necessary for the formation of stable declarative (or explicit) memory, is highly susceptible to stress. Rodent studies further indicate that stress impairs long-term potentiation (LTP), a leading candidate cellular mechanism of information storage, in the hippocampus. We have recently discovered that the amygdala plays a necessary, time-dependent role in the emergence of stress effects on hippocampal LTP and memory. Accordingly, we hypothesize that the amygdala is an important component of the central stress mechanism that regulates neurocognitive functioning. The long-term goal of this research is to construct a general experimental and theoretical basis for understanding how stress influences the hippocampus?from synaptic plasticity to neural activity to behavior?and incorporate this in a systems-level model that can organize existing data, predict new results, and generalize to other cognitive processes impacted by stress. There are four specific aims of the project: (1) an IN VITRO ANALYSIS will investigate the central stress mechanism altering hippocampal LTP;(2) a BEHAVIORAL ANALYSIS will determine the nature of central stress mechanism influencing hippocampal memory;(3) a SINGLE UNIT ANALYSIS will relate stress effects on specific behaviors with the activity of hippocampal neurons;and (4) GENERALIZATION OF THE MODEL will test whether the central stress mechanism identified in the first three aims is applicable to other types of learning and memory. Information generated from this project would be of significance (1) from a basic scientific perspective, providing valuable insights into the neuronal substrates underlying stress effects on neurocognition;and (2) from an applied perspective, providing testable hypotheses for explaining neurobiological changes that occur during stressful situations, thereby allowing insights into and treatment of various stress-related disorders that severely limit the quality of human life in today?s increasingly hectic and long-living society.

Public Health Relevance

Understanding the neurocognitive effect of stress in the hippocampus is becoming increasingly important to the nation?s health because it contributes to myriad psychopathologies. To fully understand the neurocognitive consequences of stress, it is vital to identify the basic elements of stress and their neurobiological substrates that comprise the central stress mechanism. The goal of the proposed project is to construct a general experimental and theoretical basis for understanding how stress influences the hippocampus?from synaptic plasticity to neural activity to behavior?and incorporate this in a systems-level model that can organize existing data, predict new results, and be applicable to a range of stress-associated disorders that severely limit the quality of human life in today?s increasingly hectic and long-living society.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH064457-10
Application #
8197074
Study Section
Neurobiology of Learning and Memory Study Section (LAM)
Program Officer
Rossi, Andrew
Project Start
2001-12-01
Project End
2013-11-30
Budget Start
2011-12-01
Budget End
2013-11-30
Support Year
10
Fiscal Year
2012
Total Cost
$305,214
Indirect Cost
$104,739
Name
University of Washington
Department
Psychology
Type
Schools of Arts and Sciences
DUNS #
605799469
City
Seattle
State
WA
Country
United States
Zip Code
98195
Kim, Earnest; Kim, Eun Joo; Yeh, Regina et al. (2014) Amygdaloid and non-amygdaloid fear both influence avoidance of risky foraging in hungry rats. Proc Biol Sci 281:
Kim, Eun Joo; Horovitz, Omer; Pellman, Blake A et al. (2013) Dorsal periaqueductal gray-amygdala pathway conveys both innate and learned fear responses in rats. Proc Natl Acad Sci U S A 110:14795-800
Yoon, Taejib; Graham, Lauren K; Kim, Jeansok J (2011) Hippocampal lesion effects on occasion setting by contextual and discrete stimuli. Neurobiol Learn Mem 95:176-84
Chung, Ain; Barot, Sabiha K; Kim, Jeansok J et al. (2011) Biologically predisposed learning and selective associations in amygdalar neurons. Learn Mem 18:371-4
Graham, Lauren K; Yoon, Taejib; Kim, Jeansok J (2010) Stress impairs optimal behavior in a water foraging choice task in rats. Learn Mem 17:1-4
Kim, Eun Joo; Kim, Earnest S; Covey, Ellen et al. (2010) Social transmission of fear in rats: the role of 22-kHz ultrasonic distress vocalization. PLoS One 5:e15077
Lee, Taekwan; Jarome, Tim; Li, Shi-Jiang et al. (2009) Chronic stress selectively reduces hippocampal volume in rats: a longitudinal magnetic resonance imaging study. Neuroreport 20:1554-8
Barot, Sabiha K; Chung, Ain; Kim, Jeansok J et al. (2009) Functional imaging of stimulus convergence in amygdalar neurons during Pavlovian fear conditioning. PLoS One 4:e6156
Kim, Jeansok J (2008) Serotonin, stress, and conditioning. Biol Psychiatry 63:819-20
Yoon, Taejib; Okada, Jeffrey; Jung, Min W et al. (2008) Prefrontal cortex and hippocampus subserve different components of working memory in rats. Learn Mem 15:97-105

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