Translational neuroscience measures of fear conditioning across development: applications to high-risk children and adolescents

Jovanović, Tanja; Nylocks, K. Maria; Gamwell, Kaitlyn L.

doi:10.1186/2045-5380-3-17

Cited by 15 publications

(14 citation statements)

References 98 publications

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“…In the current study, we examined whether enhanced synaptic plasticity in LB males would associate with increased fear conditioning in the juvenile period. At this age (PND28-PND29), and in accordance with our findings, rats can be conditioned to express adult-like levels of fear (Jovanovic et al, 2013). As illustrated in Figure 6, fear conditioning was successful to increase freezing in both male and female on PND28-PND29 juvenile animals.…”

Section: Behavioral Responses To Fear Conditioning In Juvenile Animalssupporting

confidence: 88%

It Is All in the Right Amygdala: Increased Synaptic Plasticity and Perineuronal Nets in Male, But Not Female, Juvenile Rat Pups after Exposure to Early-Life Stress

et al. 2020

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Early-life stress (ELS) is associated with increased vulnerability to mental disorders. The basolateral amygdala (BLA) plays a critical role in fear conditioning and is extremely sensitive to ELS. Using a naturalistic rodent model of ELS, the limited bedding paradigm (LB) between postnatal days 1-10, we previously documented that LB male, but not female preweaning rat pups display increased BLA neuron spine density paralleled with enhanced evoked synaptic responses and altered BLA functional connectivity. Since ELS effects are often sexually dimorphic and amygdala processes exhibit hemispheric asymmetry, we investigated changes in synaptic plasticity and neuronal excitability of BLA neurons in vitro in the left and right amygdala of postnatal days 22-28 male and female offspring from normal bedding or LB mothers. We report that LB conditions enhanced synaptic plasticity in the right, but not the left BLA of males exclusively. LB males also showed increased perineuronal net density, particularly around parvalbumin (PV) cells, and impaired fear-induced activity of PV interneurons only in the right BLA. Action potentials fired from right BLA neurons of LB females displayed slower maximal depolarization rates and decreased amplitudes compared with normal bedding females, concomitant with reduced NMDAR GluN1 subunit expression in the right BLA. In LB males, reduced GluA2 expression in the right BLA might contribute to the enhanced LTP. These findings suggest that LB differentially programs synaptic plasticity and PV/perineuronal net development in the left and right BLA. Furthermore, our study demonstrates that the effects of ELS exposure on BLA synaptic function are sexually dimorphic and possibly recruiting different mechanisms.

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Section: Behavioral Responses To Fear Conditioning In Juvenile Animalssupporting

confidence: 88%

It Is All in the Right Amygdala: Increased Synaptic Plasticity and Perineuronal Nets in Male, But Not Female, Juvenile Rat Pups after Exposure to Early-Life Stress

et al. 2020

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“…Findings from the extinction phase led to another discrepancy, as we did not observe the same attenuation of fear responses in our young participants as that usually observed in adults (see reviews in Delgado, Olsson, & Phelps, 2006; Dimberg & Öhman, 1996; Jovanovic, Nylocks, & Gamwell, 2013; Ohman, 2009; Sehlmeyer et al, 2009). Indeed, resistance to fear extinction was observed in fear ratings for male faces in both boys and girls, and in SCRs of boys who viewed male faces.…”

Section: Discussioncontrasting

confidence: 69%

The conditioning and extinction of fear in youths: What's sex got to do with it?

Chauret

Buissonnière-Ariza

Tremblay

et al. 2014

Biological Psychology

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Adult work shows differences in emotional processing influenced by sexes of both the viewer and expresser of facial expressions. We investigated this in 120 healthy youths (57 boys; 10–17 years old) randomly assigned to fear conditioning and extinction tasks using either neutral male or female faces as the conditioned threat and safety cues, and a fearful face paired with a shrieking scream as the unconditioned stimulus. Fear ratings and skin conductance responses (SCRs) were assessed. Male faces triggered increased fear ratings in all participants during conditioning and extinction. Greater differential SCRs were observed in boys viewing male faces and in girls viewing female faces during conditioning. During extinction, differential SCR findings remained significant in boys viewing male faces. Our findings demonstrate how sex of participant and sex of target interact to shape fear responses in youths, and how the type of measure may lead to distinct profiles of fear responses.

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“…In support of this, adolescent social isolation has been shown to increase anxiety-like behaviors (Chappell et al, 2013; Hall et al, 1998b; Hellemans et al, 2004; Yorgason et al, 2013) and ethanol self-administration (Chappell et al, 2013; Deehan et al, 2007; Ehlers et al, 2007; Hall et al, 1998a; McCool and Chappell, 2009) in adult rats. The experiments described herein extend previous studies by using the fear-potentiated startle paradigm, a highly translational and clinically relevant measure of fear learning (Grillon, 2008; Jovanovic et al, 2013), to examine whether adolescent isolation also produces disruptions in fear and extinction learning. Specifically, we hypothesized that adolescent social isolation would disrupt extinction memory acquisition following fear conditioning, as extinction learning is known to be disrupted among individuals suffering from PTSD (Grillon and Morgan, 1999; Jovanovic et al, 2010).…”

Section: Introductionmentioning

confidence: 74%

Adolescent social isolation increases anxiety-like behavior and ethanol intake and impairs fear extinction in adulthood: Possible role of disrupted noradrenergic signaling

et al. 2015

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Alcohol use disorder, anxiety disorders, and post-traumatic stress disorder (PTSD) are highly comorbid, and exposure to chronic stress during adolescence may increase the incidence of these conditions in adulthood. Efforts to identify the common stress-related mechanisms driving these disorders have been hampered, in part, by a lack of reliable preclinical models that replicate their comorbid symptomatology. Prior work by us, and others, has shown that adolescent social isolation increases anxiety-like behaviors and voluntary ethanol consumption in adult male Long-Evans rats. Here we examined whether social isolation also produces deficiencies in extinction of conditioned fear, a hallmark symptom of PTSD. Additionally, as disrupted noradrenergic signaling may contribute to alcoholism, we examined the effect of anxiolytic medications that target noradrenergic signaling on ethanol intake following adolescent social isolation. Our results confirm and extend previous findings that adolescent social isolation increases anxiety-like behavior and enhances ethanol intake and preference in adulthood. Additionally, social isolation is associated with a significant deficit in the extinction of conditioned fear and a marked increase in the ability of noradrenergic therapeutics to decrease ethanol intake. These results suggest that adolescent social isolation not only leads to persistent increases in anxiety-like behaviors and ethanol consumption, but also disrupts fear extinction, and as such may be a useful preclinical model of stress-related psychopathology. Our data also suggest that disrupted noradrenergic signaling may contribute to escalated ethanol drinking following social isolation, thus further highlighting the potential utility of noradrenergic therapeutics in treating the deleterious behavioral sequelae associated with early life stress.

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Translational neuroscience measures of fear conditioning across development: applications to high-risk children and adolescents

Cited by 15 publications

References 98 publications

It Is All in the Right Amygdala: Increased Synaptic Plasticity and Perineuronal Nets in Male, But Not Female, Juvenile Rat Pups after Exposure to Early-Life Stress

It Is All in the Right Amygdala: Increased Synaptic Plasticity and Perineuronal Nets in Male, But Not Female, Juvenile Rat Pups after Exposure to Early-Life Stress

The conditioning and extinction of fear in youths: What's sex got to do with it?

Adolescent social isolation increases anxiety-like behavior and ethanol intake and impairs fear extinction in adulthood: Possible role of disrupted noradrenergic signaling

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