Cellular and oscillatory substrates of fear extinction learning

Davis, Patrick; Zaki, Yosif; Maguire, Jamie; Reijmers, Leon G.

doi:10.1038/nn.4651

Cited by 111 publications

(200 citation statements)

References 50 publications

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“…It has been reported that the amygdala is a vital brain area correlated with the social and fear-related behaviors (Bickart et al, 2011). In particular, it was found that BLA actively participated in fear extinction processing, and the aberrant neuronal activation in the BLA was implicated in enhanced fear extinction (Bocchio et al, 2017;Davis et al, 2017). Thus, we hypothesized that neuronal activation in the BLA may be decreased by co-housing with a receptive mating partner.…”

Section: Resultsmentioning

confidence: 96%

Social Company by a Receptive Mating Partner Facilitates Fear Extinction

et al. 2020

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Fear extinction remains an unresolved challenge for behavioral exposure therapy in patients with post-traumatic stress disorder (PTSD). Previous reports have suggested that social support from either familiar or unfamiliar same-sex partners is beneficial to attenuating fear responses during fear extinction and renewal. Despite that, few studies have examined the effects of social support in advance on fear extinction and/or retrieval. It is also not clear whether social company by a receptive mating partner in advance facilitates fear extinction. In the present study, we address these questions by introducing a co-housing method, where fear-conditioned male mice are co-housed with or without a receptive mating partner prior to fear extinction. We found that while co-housing with an ovariectomized female mouse showed little effect on fear extinction or retrieval, social company by a receptive mating partner in advance dramatically facilitates fear extinction. In addition, the number of cFos-positive neurons in the basolateral amygdala (BLA) were also found to be reduced in male mice accompanied with receptive mating partner in response to fear extinction and retrieval, indicating diminished neuronal activation. Electrophysiological studies further showed that the excitability of excitatory neurons in BLA was decreased, which is probably due to the attenuated basal level of excitatory synaptic transmission. Together, our observations demonstrate an effect of social company by a receptive mating partner can facilitate fear extinction and afford a possible cellular mechanism.

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Section: Resultsmentioning

confidence: 96%

Social Company by a Receptive Mating Partner Facilitates Fear Extinction

et al. 2020

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“…Communication between the PFC and BLA occurs, in part, through oscillations, which can be manipulated and evoked using train frequency stimulations to understand the contribution of different oscillatory patterns between the PFC and BLA. Some of these oscillations from the PFC to the BLA are believed to be regulated by and sufficient to recruit inhibitory networks regulating fear expression [40,41]. While the current cortical train stimulation frequency (20 Hz) was chosen based on developmental differences between adults and adolescents seen throughout the BLA, future work should investigate the contribution of various frequency train ranges [18].…”

Section: Discussionmentioning

confidence: 99%

Fear Learning Enhances Prefrontal Cortical Suppression of Auditory Thalamic Inputs to the Amygdala in Adults, but Not Adolescents

Ferrara

Mrackova

Loh

et al. 2020

IJMS

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Adolescence is characterized by increased susceptibility to the development of fear- and anxiety-related disorders. Adolescents also show elevated fear responding and aversive learning that is resistant to behavioral interventions, which may be related to alterations in the circuitry supporting fear learning. These features are linked to ongoing adolescent development of medial prefrontal cortical (PFC) inputs to the basolateral amygdala (BLA) that regulate neural activity and contribute to the refinement of fear responses. Here, we tested the hypothesis that the extent of PFC inhibition of the BLA following fear learning is greater in adults than in adolescents, using anesthetized in vivo recordings to measure local field potentials (LFPs) evoked by stimulation of PFC or auditory thalamic (MgN) inputs to BLA. We found that BLA LFPs evoked by stimulation of MgN inputs were enhanced in adults following fear conditioning. Fear conditioning also led to reduced summation of BLA LFPs evoked in response to PFC train stimulation, and increased the capacity of PFC inhibition of MgN inputs in adults. These data suggest that fear conditioning recruits additional inhibitory capacity by PFC inputs to BLA in adults, but that this capacity is weaker in adolescents. These results provide insight into how the development of PFC inputs may relate to age differences in memory retention and persistence following aversive learning.

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“…Consistent with this prior work, we found that LB led to an earlier rise in PV+ cell density in BLA, with PV+ cell density being higher in LB reared mice compared to controls at PND 21. PV+ neuronal activity in the BLA has been shown to be capable of modulating fear expression (Wolff et al, 2014;Davis et al, 2017) . In addition, PV+ cell density has previously been shown to negatively correlate with innate threat responses in post-weaned rats (Santiago et al, 2018) .…”

Section: Discussionmentioning

confidence: 99%

“…To understand the neural basis of the suppressed fear expression at PND 21, we focused on the potential role of the premature differentiation of PV+ neurons in the BLA ( Figure 2A ). The focus on PV+ cells is related to previous reports that have demonstrated a role for BLA PV+ cells in modulating fear expression (Wolff et al, 2014;Davis et al, 2017) . Therefore, we hypothesized that the early emergence of PV+ cells in the pre-adolescent BLA may be leading to the decreased fear expression observed at PND 22.…”

Section: Pv Inhibition In Bla Rescues Fear Expression Deficitsmentioning

confidence: 99%

Early life adversity decreases fear expression in pre-adolescence by accelerating amygdalar parvalbumin cell development

Manzano-Nieves

Bravo

Bath

2020

Preprint

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KeywordsEarly life stress medial prefrontal cortex amygdala development fear conditioning AbstractResource insecurity (e.g., poverty) can be a significant source of stress.Decreased resources during childhood has been associated with increased risk for developing stress-related disorders, including major depressive disorder and anxiety Although the link between early life adversity and increased risk for psychopathology has been well established, the developmental mechanisms remain unclear . Using a mouse model of poverty-like rearing, limited bedding and nesting materials (LB), we tested the effects of LB on the development of fear learning and of key neuronal structures involved in emotional regulation, the medial prefrontal cortex (mPFC) and basolateral amygdala (BLA). LB delayed the ability of pre-adolescent mice to express, but not form, an auditory conditioned fear memory. LB disrupted typical fear circuit development, accelerating parvalbumin positive (PV+) inhibitory interneuron maturation in the BLA and delaying the maturation of connections between the mPFC and BLA. The decreased fear expression in LB reared mice during early development was rescued through optogenetic inactivation of PV+ cells in the BLA. Together our data demonstrate that LB has profound and deleterious effects on mPFC and BLA development, decreasing threat-associated behavior expression, but not learning, in childhood. The current results provide a model of transiently blunt emotional reactivity in childhood, with fear-associated memories emerging later in adolescence, and possibly contributing to later pathology development.

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Cellular and oscillatory substrates of fear extinction learning

Cited by 111 publications

References 50 publications

Social Company by a Receptive Mating Partner Facilitates Fear Extinction

Social Company by a Receptive Mating Partner Facilitates Fear Extinction

Fear Learning Enhances Prefrontal Cortical Suppression of Auditory Thalamic Inputs to the Amygdala in Adults, but Not Adolescents

Early life adversity decreases fear expression in pre-adolescence by accelerating amygdalar parvalbumin cell development

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