Stress-induced alterations of learning and memory have important implications for understanding the development of post-traumatic stress disorder (PTSD). Researchers have speculated that traumatic stress may promote the onset of PTSD as a result of pre-existing genetic factors and peri-traumatic physiological responses influencing learning and, thus, traumatic memory formation. Indeed, investigators have established a clear association between certain genetic polymorphisms, emotional memory and the onset of PTSD. However, systematic examination, in clinical samples, of susceptibility factors that could promote traumatic memory formation is problematic, making basic models of stress-memory interactions a necessity. It is still unclear as to what factors are most important for dictating te types of effects stress exerts on learning and memory and when the effects promote the formation of intrusive, debilitating memories. One leading theory regarding stress effects on learning is the temporal dynamics model of emotional memory processing. According to this theory, stress exerts biphasic effects on learning as a result of amygdala-induced modulation of hippocampal synaptic plasticity. Specifically, stress rapidly activates the amygdala, which enhances hippocampal plasticity and promotes the formation of powerful emotional memories; however, as stress continues, the hippocampus enters a refractory state during which hippocampal plasticity, and thus learning, is impaired. We have preliminary data supporting these predictions for declarative learning in humans; however, the mechanisms underlying these effects are still unclear, and an examination of how stressor timing influences other forms of learning that may relate better to traumatic memory formation, such as fear conditioning and extinction, has not yet been conducted. Moreover, sex differences are common in the stress-memory literature, yet little work has examined the role of sex in time-dependent effects of stress on learning. Thus, in Aim 1, we will examine how the timing of pre-learning stress interacts with individual characteristics (e.g., autonomic and endocrine stress responses, sex) to influence declarative learning and fear conditioning. Since there has been little work examining how genetic polymorphisms associated with emotional memory and stress increases one's risk for traumatic memory formation, this will be the focus of Aim 2. We will genotype participants from the studies in Aim 1 for single nucleotide polymorphisms (SNPs) that have been associated with the physiological stress response, emotional memory and/or risk for PTSD and examine whether such SNPs are associated with participants' physiological response to/recovery from stress exposure, as well as any observed stress-induced alterations of learning and memory. These studies will contribute important knowledge about when stress enhances versus impairs learning and memory and the physiological mechanisms underlying such effects. The findings may also lend insight into risk factors for traumatic memory formation and potentially facilitate the development of more targeted treatment options for PTSD in the future.

Public Health Relevance

The proposed studies will provide important information about how the timing of stress interacts with genetic and physiological characteristics of an individual to influence human learning. This could provide new insights into traumatic memory formation and ultimately lead to novel, more targeted, treatment options for people with PTSD.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Academic Research Enhancement Awards (AREA) (R15)
Project #
1R15MH104836-01A1
Application #
8851344
Study Section
Biobehavioral Mechanisms of Emotion, Stress and Health Study Section (MESH)
Program Officer
Tuma, Farris K
Project Start
2015-03-01
Project End
2018-02-28
Budget Start
2015-03-01
Budget End
2018-02-28
Support Year
1
Fiscal Year
2015
Total Cost
$423,776
Indirect Cost
$123,776
Name
Ohio Northern University
Department
Psychology
Type
Schools of Arts and Sciences
DUNS #
051625564
City
Ada
State
OH
Country
United States
Zip Code
45810
Zoladz, Phillip R; Dailey, Alison M; Nagle, Hannah E et al. (2017) FKBP5 polymorphisms influence pre-learning stress-induced alterations of learning and memory. Eur J Neurosci 45:648-659
Zoladz, Phillip R; Cadle, Chelsea E; Dailey, Alison M et al. (2017) Blunted cortisol response to acute pre-learning stress prevents misinformation effect in a forced confabulation paradigm. Horm Behav 93:1-8
Zoladz, Phillip R; Dailey, Alison M; Nagle, Hannah E et al. (2017) ADRA2B deletion variant influences time-dependent effects of pre-learning stress on long-term memory. Neurobiol Learn Mem 140:71-81