Memory impairments constitute a major problem in society. These occur naturally with aging and as a result of diseases (e.g., Alzheimer's disease), and are exacerbated by stress. The hippocampus, as part of a brain system necessary for the formation of stable declarative (or explicit) memory appears to be prominently susceptible to uncontrollable stress. Recent rodent studies demonstrate that stress interferes with learning of hippocarnpal-dependent spatial memory and alters the inducibility of long-term potentiation (LTP) and long-term depression (LTD)--two putative synaptic mechanisms of information storage-in the hippocampus. Other studies indicate that the amygdala is critically involved in coordinating stress-related behaviors and modulating hippocampal functioning. Our long-term goal is to understand the amygdalar mechanisms involved in mediating stress effects on hippocampal functioning.There are three specific aims of the project: (1) an IN VITRO ANALYSIS will investigate the role of the amygdala in mediating stress effects on hippocampal LTP/LTD; (2) a BEHAVIORAL ANALYSIS will examine the amygdalar mechanisms mediating stress-induced impairments in hippocampal-dependent spatial memory; and (3) a SINGLE UNIT ANALYSIS of hippocampal place cells will integrate stress effects on hippocampal plasticity and spatial memory. These related aims are designed to test our current working hypothesis that stress-induced alterations in hippocampal functioning are due to excessive activity exerted by the amygdala onto the hippocampus during stress.Data obtained from this project would be of significance (1) from a basic scientific perspective providing valuable information concerning how hippocampal plasticity might be regulated by naturalistic factors (such as stress) and the underlying mechanisms subserving stress effects on hippocampal functioning; and (2) from an applied perspective, providing important insights that will assist in developing therapeutic approaches to alleviate cognitive impairments associated with stress-induced ailments (such as anxiety, posttraumatic stress disorder, vascular dementia) that severely limit the quality of human life.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Research Project (R01)
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Special Emphasis Panel (ZRG1-IFCN-1 (02))
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Anderson, Kathleen C
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University of Washington
Schools of Arts and Sciences
United States
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Huh, Yeowool; Jung, Dahee; Seo, Taeyoon et al. (2018) Brain stimulation patterns emulating endogenous thalamocortical input to parvalbumin-expressing interneurons reduce nociception in mice. Brain Stimul 11:1151-1160
Kim, Eun Joo; Pellman, Blake; Kim, Jeansok J (2015) Stress effects on the hippocampus: a critical review. Learn Mem 22:411-6
Park, Mijeong; Kim, Chong-Hyun; Jo, Seonmi et al. (2015) Chronic Stress Alters Spatial Representation and Bursting Patterns of Place Cells in Behaving Mice. Sci Rep 5:16235
Pellman, Blake A; Kim, Earnest; Reilly, Melissa et al. (2015) Time-Specific Fear Acts as a Non-Photic Entraining Stimulus of Circadian Rhythms in Rats. Sci Rep 5:14916
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
Kosten, Therese A; Kim, Jeansok J; Lee, Hongjoo J (2012) Early life manipulations alter learning and memory in rats. Neurosci Biobehav Rev 36:1985-2006
Kim, Eun Joo; Kim, Earnest S; Park, Mijeong et al. (2012) Amygdalar stimulation produces alterations on firing properties of hippocampal place cells. J Neurosci 32:11424-34
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

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