An Adolescent Sensitive Period for Threat Responding: Impacts of Stress and Sex

Gerhard, Danielle M.; Meyer, Heidi C.; Lee, Francis S.

doi:10.1016/j.biopsych.2020.10.003

Cited by 30 publications

(15 citation statements)

References 84 publications

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“…Therefore, given the overlap of the neurocircuitry of fear (e.g., mPFC, HP, BLA) with the neurocircuitry of cognitive and emotional behaviors, it is not surprising that AIE-induced alterations in anxiety and cognition also extend to long-term alterations in threat responding. Adolescence is a period during which threat monitoring/response and the neurocircuits that mediate this behavior are highly plastic and undergoing rapid changes ( Gerhard et al, 2021 ), and emotional experiences during this time can profoundly shape long-term functioning of the neurocircuitry that mediates affective behavior. Thus, our observation may have important translational implications as difficulties in assessing and appropriately responding to potential threats is a key feature of many psychiatric disorders that may be impacted by a history of adolescent alcohol abuse.…”

Section: Discussionmentioning

confidence: 99%

Adolescent Alcohol Exposure Results in Sex-specific Alterations in Conditioned Fear Learning and Memory in Adulthood

2022

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The present study used auditory fear conditioning to assess the impact of repeated binge-like episodes of alcohol exposure during adolescence on conditioned fear in adulthood. Male and female Long-Evans rats were subjected to adolescent intermittent ethanol (AIE) exposure by vapor inhalation between post-natal day 28 and 44. After aging into adulthood, rats then underwent fear conditioning by exposure to a series of tone-shock pairings. This was followed by cued-tone extinction training, and then testing of fear recovery. In male rats, AIE exposure enhanced conditioned freezing but did not alter the time-course of extinction of cued-tone freezing. During subsequent assessment of fear recovery, AIE exposed rats exhibited less freezing during contextual fear renewal, but greater freezing during extinction recall and spontaneous recovery. Compared to males, female rats exhibited significantly lower levels of freezing during fear conditioning, more rapid extinction of freezing behavior, and significantly lower levels of freezing during the tests of fear recovery. Unlike males that were all classified as high conditioners; female rats could be parsed into either a high or low conditioning group. However, irrespective of their level of conditioned freezing, both the high and low conditioning groups of female rats exhibited rapid extinction of conditioned freezing behavior and comparatively low levels of freezing in tests of fear recovery. Regardless of group classification, AIE had no effect on freezing behavior in female rats during acquisition, extinction, or fear recovery. Lastly, exposure of male rats to the mGlu5 positive allosteric modulator CDPPB prevented AIE-induced alterations in freezing. Taken together, these observations demonstrate sex-specific changes in conditioned fear behaviors that are reversible by pharmacological interventions that target mGlu5 receptor activation.

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Section: Discussionmentioning

confidence: 99%

Adolescent Alcohol Exposure Results in Sex-specific Alterations in Conditioned Fear Learning and Memory in Adulthood

2022

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“…Thus as early as the neonatal stage, rodents are able to manifest their threat/fear with ultrasonic vocalizations (USV with a peak at PND6-8) [42], and freezing behavior and unconditioned startle responses emerge later on during the second postnatal week [42]. Then, the typical development of fear follows a linear pattern with adolescence characterized by a period of heightened emotional reactivity [43][44][45]. The development of anxiety-like responses (i.e., behavioral responses occurring when an individual copes with a potentially dangerous situation and not with explicit immediate threats) seems to be delayed and emerges around weaning (PND21) to reach adult-like levels in young adult rats (PND56 [46]).…”

Section: The Physiological Function Of Adult Hippocampal Neurogenesismentioning

confidence: 99%

A Baldwin interpretation of adult hippocampal neurogenesis: from functional relevance to physiopathology

2021

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Hippocampal adult neurogenesis has been associated to many cognitive, emotional, and behavioral functions and dysfunctions, and its status as a selected effect or an “appendix of the brain” has been debated. In this review, we propose to understand hippocampal neurogenesis as the process underlying the “Baldwin effect”, a particular situation in evolution where fitness does not rely on the natural selection of genetic traits, but on “ontogenetic adaptation” to a changing environment. This supports the view that a strong distinction between developmental and adult hippocampal neurogenesis is made. We propose that their functions are the constitution and the lifelong adaptation, respectively, of a basic repertoire of cognitive and emotional behaviors. This lifelong adaptation occurs through new forms of binding, i.e., association or dissociation of more basic elements. This distinction further suggests that a difference is made between developmental vulnerability (or resilience), stemming from dysfunctional (or highly functional) developmental hippocampal neurogenesis, and adult vulnerability (or resilience), stemming from dysfunctional (or highly functional) adult hippocampal neurogenesis. According to this hypothesis, developmental and adult vulnerability are distinct risk factors for various mental disorders in adults. This framework suggests new avenues for research on hippocampal neurogenesis and its implication in mental disorders.

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“…These findings suggest MIA contributes to an impairment in the offspring’s ability to discriminate between “safe” trials (without CS presentation) and “stressful” trials (with CS presentation). Early life stress has been shown to impair this form of contextual threat detection in adolescence, and this is especially true for females (Manzano-Nieves et al, 2018; Gerhard et al, 2020). These results, in addition to reduced neonatal huddling, point to generally impaired sensory processing and threat response in the offspring of dams exposed to MIA during lactation.…”

Section: Discussionmentioning

confidence: 99%

Got Milk? Maternal immune activation during the mid-lactational period affects nutritional milk quality and adolescent offspring sensory processing in male and female rats

DeRosa

Tran

Kentner

2022

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The neonatal environment requires a high level of maternal demand in terms of both breastfeeding and other forms of maternal care. Previous studies have underscored the importance of these maternal factors on offspring development and behavior. However, their contribution as dynamic variables in animal models of early life stress are often overlooked. In the present study, we show that lipopolysaccharide (LPS)-induced maternal immune activation (MIA) on postnatal day (P)10 immediately elevated milk corticosterone concentrations, which recovered by P11. In contrast, both milk triglyceride and percent creamatocrit values demonstrated a prolonged decrease following inflammatory challenge. Sustained inflammatory-induced changes to the nutritional quality of milk were also evidenced by its composition of microbial communities associated with inefficient energy and lipid metabolism. Nutritional deficits in early development have been associated with metabolic dysfunction later in life. Indeed, MIA-associated changes in the nutritional profile of milk were reflected by increased adolescent offspring bodyweights. While MIA did not decrease maternal care quality, there was a significant compensatory increase in maternal licking and grooming the day that followed the inflammatory challenge. However, this did not protect against disrupted neonatal huddling or later-life alterations in sensorimotor gating and mechanical allodynia in MIA offspring. Animal models of early life stress can impact both parents and their offspring. One mechanism that can mediate the effects of such stressors is changes to maternal lactation quality which our data show can confer multifaceted and compounding effects on offspring physiology and behavior.

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An Adolescent Sensitive Period for Threat Responding: Impacts of Stress and Sex

Cited by 30 publications

References 84 publications

Adolescent Alcohol Exposure Results in Sex-specific Alterations in Conditioned Fear Learning and Memory in Adulthood

Adolescent Alcohol Exposure Results in Sex-specific Alterations in Conditioned Fear Learning and Memory in Adulthood

A Baldwin interpretation of adult hippocampal neurogenesis: from functional relevance to physiopathology

Got Milk? Maternal immune activation during the mid-lactational period affects nutritional milk quality and adolescent offspring sensory processing in male and female rats

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