From memory impairment to posttraumatic stress disorder-like phenotypes: The critical role of an unpredictable second traumatic experience

Charles Finsterwald, Adam B. Steinmetz, Alessio Travaglia, Cristina Alberini

Research output: Contribution to journalArticle

Abstract

Arousal and stress critically regulate memory formation and retention. Increasing levels of stress produce an inverted U-shaped effect on cognitive performance, including the retention of explicit memories, and experiencing a severe stress during a traumatic event may lead to posttraumatic stress disorder (PTSD). The molecular mechanisms underlying the impairing effect of a severe stress on memory and the key contribution of traumatic experiences toward the development of PTSD are still unknown. Here, using increasing footshock intensities in an inhibitory avoidance paradigm, we reproduced the inverted U-shaped curve of memory performance in rats. We then show that the inverted U profile of memory performance correlates with an inverted U profile of corticosterone level in the circulation and of brain-derived neurotrophic factor, phosphorylated tropomyosin-receptor kinase B, and methyl CpG binding protein in the dorsal hippocampus. Furthermore, training with the highest footshock intensity (traumatic experience) led to a significant elevation of hippocampal glucocorticoid receptors. Exposure to an unpredictable, but not to a predictable, highly stressful reminder shock after a first traumatic experience resulted in PTSD-like phenotypes, including increased memory of the trauma, high anxiety, threat generalization, and resistance to extinction. Systemic corticosterone injection immediately after the traumatic experience, but not 3 d later, was sufficient to produce PTSD-like phenotypes. We suggest that, although after a first traumatic experience a suppression of the corticosterone- dependent response protects against the development of an anxiety disorder, experiencing more than one trauma (multiple hits) is a critical contributor to the etiology of PTSD.

Original languageEnglish (US)
Pages (from-to)15903-15915
Number of pages13
JournalJournal of Neuroscience
Volume35
Issue number48
DOIs
StatePublished - Dec 2 2015

Fingerprint

Post-Traumatic Stress Disorders
Phenotype
Corticosterone
Multiple Trauma
Brain-Derived Neurotrophic Factor
Glucocorticoid Receptors
Arousal
Anxiety Disorders
Shock
Hippocampus
Carrier Proteins
Anxiety
Injections
Wounds and Injuries

Keywords

  • Hippocampus
  • Memory
  • Molecular mechanisms
  • PTSD
  • Stress
  • Trauma

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

From memory impairment to posttraumatic stress disorder-like phenotypes : The critical role of an unpredictable second traumatic experience. / Finsterwald, Charles; Steinmetz, Adam B.; Travaglia, Alessio; Alberini, Cristina.

In: Journal of Neuroscience, Vol. 35, No. 48, 02.12.2015, p. 15903-15915.

Research output: Contribution to journalArticle

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