Impact of Life History on Fear Memory and Extinction

Abstract

Behavioral profiles are strongly shaped by an individual's whole life experience. The accumulation of negative experiences over lifetime is thought to promote anxiety-like behavior in adulthood (“allostatic load hypothesis”). In contrast, the “mismatch hypothesis” of psychiatric disease suggests that high levels of anxiety-like behavior are the result of a discrepancy between early and late environment. The aim of the present study was to investigate how different life histories shape the expression of anxiety-like behavior and modulate fear memory. In addition, we aimed to clarify which of the two hypotheses can better explain the modulation of anxiety and fear. For this purpose, male mice grew up under either adverse or beneficial conditions during early phase of life. In adulthood they were further subdivided in groups that either matched or mismatched the condition experienced before, resulting in four different life histories. The main results were: (i) Early life benefit followed by late life adversity caused decreased levels of anxiety-like behavior. (ii) Accumulation of adversity throughout life history led to impaired fear extinction learning. Late life adversity as compared to late life benefit mainly affected extinction training, while early life adversity as compared to early life benefit interfered with extinction recall. Concerning anxiety-like behavior, the results do neither support the allostatic load nor the mismatch hypothesis, but rather indicate an anxiolytic effect of a mismatched early beneficial and later adverse life history. In contrast, fear memory was strongly affected by the accumulation of adverse experiences over the lifetime, therefore supporting allostatic load hypothesis. In summary, this study highlights that anxiety-like behavior and fear memory are differently affected by specific combinations of adverse or beneficial events experienced throughout life.

Varying Social Experiences in Adulthood Do Not Differentially Affect Anxiety-Like Behavior But Stress Hormone Levels

“…Thus, escapable adversity resulted in relatively low levels of anxiety compared to the other experimental groups but only in animals that had experienced benefits during previous life stages (Bodden et al, 2015 ). This finding was confirmed in a follow-up study (Remmes et al, 2016 ). Additionally, a second follow-up study revealed corresponding differences in the expression of genes associated with anxiety and stress circuits (Bodden et al, 2017 ).…”

“…In previous studies, we have shown escapable social defeat in early adulthood to result in relatively low levels of anxiety, if mice had experienced benefits during early life, i.e., in the pre- and early postnatal period as well as adolescence (designated as “coping with challenge effect”; Remmes et al, 2016 ; Bodden et al, 2015 ). The major aim of the present study was to elucidate, whether this specific combination of experiences—benefits followed by escapable adversity—is sufficient for the occurrence of the “coping with challenge” effect or whether the phases of life during which these experiences are made are also important.…”

“…Please note that we were not mainly interested in how previous social experience affects following social experience, but in how combinations of social experiences affect levels of anxiety-like behavior. The experimental design (see Figure 1 ) was based on previous work describing such an effect in earlier life phases (Bodden et al, 2015 ; Remmes et al, 2016 ).…”

“…It states that coping with adversity (i.e., escapable social defeat) leads to relatively low levels of anxiety when following beneficial experiences in early life stages, but not when following adverse experiences. Interestingly, this effect seems to be specific to anxiety-like behavior: fear extinction seems to be affected in a different way than anxiety-like behavior by combinations of adverse and beneficial social experience (Remmes et al, 2016 ). For the described effect on anxiety, we assume that the controllability of the adverse experience is crucial.…”

A Time to Wean? Impact of Weaning Age on Anxiety-Like Behaviour and Stability of Behavioural Traits in Full Adulthood

“…If so, body weight changes are in line with previous findings in mice, showing that mildly adverse experiences during different stages of life lead to an increase in body weights afterwards. For example, exposure to olfactory cues of unfamiliar adult males during the prenatal and suckling period caused significantly higher body weights at the time of weaning compared to a control treatment [46]. Similarly, loser experiences as compared to mating experiences during adolescence and in later life were associated with higher body weights afterwards [38, 47].…”