Preferential recruitment of the basolateral amygdala during memory encoding of negative scenes in posttraumatic stress disorder

Patel, Ronak; Girard, Todd A.; Pukay‐Martin, Nicole D.; Monson, Candice M.

doi:10.1016/j.nlm.2016.02.003

Cited by 24 publications

(45 citation statements)

References 55 publications

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“…Fos was increased in the BLA (ANOVA BLA: F (3,22) =70.67, p<0.0001; post hoc Tukey tests: p<0.05 vs naive, p<0.05 vs FC, p<0.05 vs SR), which participates in fear memory storage and expression (54–58). Importantly, a signature of PTSD is dysfunctional activation and connectivity of these regions (59, 60). …”

Section: Resultsmentioning

confidence: 99%

Susceptibility and Resilience to Posttraumatic Stress Disorder–like Behaviors in Inbred Mice

Sillivan

Joseph

Jamieson

et al. 2017

Biological Psychiatry

100

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Background The limited neurobiological understanding of PTSD has been partially attributed to the need for improved animal models. Stress-enhanced fear learning (SEFL) in rodents recapitulates many PTSD-associated behaviors, including stress-susceptible (SS) and –resilient (SR) subgroups in outbred rats. Identification of subgroups requires additional behavioral phenotyping, a confound to mechanistic studies. Methods We employed a SEFL paradigm in inbred male and female C57BL/6 that combines acute stress with fear conditioning to precipitate “traumatic” memories. Extinction and long-term retention of extinction were examined after SEFL. Further characterization of SEFL effects on male mice was performed with additional behavioral tests, determination of regional activation by Fos immunofluorescence and RNA-sequencing of the basolateral amygdala (BLA). Results Stressed animals displayed persistently elevated freezing during extinction. While more uniform in females, SEFL produced male subgroups with differential susceptibility that were identified without post-training phenotyping. Additional phenotyping of males revealed PTSD-associated behaviors, including extinction-resistant fear memory, hyperarousal, generalization and dysregulated corticosterone in SS males. Altered Fos activation was also seen in the infralimbic cortex and BLA of SS males after remote memory retrieval. Key behavioral outcomes, including susceptibility, were replicated by two independent laboratories. RNA-sequencing of the BLA revealed transcriptional divergence between the male subgroups, including genes with reported polymorphic association to PTSD patients. Conclusions This SEFL model provides a tool for development of PTSD therapeutics that is compatible with the growing number of mouse-specific resources. Furthermore, use of an inbred strain allows for investigation into epigenetic mechanisms that are expected to critically regulate susceptibility and resilience.

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Section: Resultsmentioning

confidence: 99%

Susceptibility and Resilience to Posttraumatic Stress Disorder–like Behaviors in Inbred Mice

Sillivan

Joseph

Jamieson

et al. 2017

Biological Psychiatry

100

View full text Add to dashboard Cite

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“…Moreover, whereas increased spinogenesis and dendritic growth of principal and stellate neurons have been reported in the BLA following severe stress 16,17 , a loss of stellate neuron spines may occur in the CMA nuclei 18,19 . Finally, preliminary findings from human functional imaging studies suggest that the BLA and the CMA differ in terms of activity 20 and functional connectivity 21 in PTSD, further suggesting that these complexes should be considered separately in trauma-and stress-related disorders 40,41 .…”

Section: Discussionmentioning

confidence: 99%

“…The results from animal models indicate distinct responses of the BLA 16,17 and CMA 18,19 complex to chronic or severe stress, and functional MRI studies in humans suggest that the BLA and the CMA differ in terms of activity 20 and functional connectivity 21 in PTSD. This renders it likely that the nuclei of the two amygdala complexes may be differently associated with PTSD.…”

Section: Introductionmentioning

confidence: 98%

The association of PTSD symptom severity with amygdala nuclei volumes in traumatized youths

et al. 2020

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The amygdala is a core component in neurobiological models of stress and stress-related pathologies, including posttraumatic stress disorder (PTSD). While numerous studies have reported increased amygdala activity following traumatic stress exposure and in PTSD, the findings regarding amygdala volume have been mixed. One reason for these mixed findings may be that the amygdala has been considered as a homogenous entity, while it in fact consists of several nuclei with unique cellular and connectivity profiles. Here, we investigated amygdala nuclei volumes of the basolateral and the centrocorticomedial complex in relation to PTSD symptom severity in 47 young survivors from the 2011 Norwegian terror attack 24-36 months post-trauma. PTSD symptoms were assessed 4-5, 14-15 and 24-36 months following the trauma. We found that increased PTSD symptom severity 24-36 months post-trauma was associated with volumetric reductions of all basolateral as well as the central and the medial nuclei. However, only the lateral nucleus was associated with longitudinal symptom development, and mediated the association between 4-5 months and 24-36 months post-trauma symptoms. The results suggest that the amygdala nuclei may be differentially associated with cross-sectional and longitudinal measures of PTSD symptom severity. As such, investigations of amygdala total volume may not provide an adequate index of the association between amygdala and stress-related mental illness.

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“…The current rsFC study sample ( N = 24) comprised participants participating in larger studies of recently traumatized individuals; task-related fMRI data are reported by Patel, Girard, Pukay-Martin, and Monson [ 35 ]. Participant demographics and clinical characteristics are summarized in Table 1 .…”

Section: Methodsmentioning

confidence: 99%

Functional connectivity of hippocampal subregions in PTSD: relations with symptoms

et al. 2018

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BackgroundPosttraumatic stress disorder (PTSD) is associated with abnormal hippocampal activity; however, the functional connectivity (FC) of the hippocampus with other brain regions in PTSD and its relations with symptoms warrants further attention. We investigated subregional hippocampal FC in PTSD during a resting state compared with a trauma-exposed control (TEC) group. Based on extant research, we targeted the FCs of the anterior and posterior hippocampal subregions with the amygdala, medial prefrontal cortex (mPFC), and the posterior cingulate (PCC).MethodsResting-state functional magnetic resonance images were acquired from 11 individuals with PTSD and 13 trauma-exposed controls. Anterior and posterior hippocampal FC was compared between groups. Within the PTSD and TEC groups, subregional hippocampal FC was correlated with scores on the Clinician-Administered PTSD Scale (CAPS) at time of scan and 4 months post-scan.ResultsThose with PTSD had significantly greater FC compared with the TEC group between the left posterior hippocampus and the bilateral PCC (g’s > .96). Direct contrasts of the Fisher z-transformed coefficients indicated that the correlations between CAPS scores 4 months post scan and the FC between the left hippocampal head and the right PCC (z = − 2.07, p = .039) as well as the FC between the right hippocampal tail and the right mPFC (z = − 2.19, p = .029) were significantly greater in the PTSD group compared to the TEC group.ConclusionsThese results support between-group differences in posterior hippocampal FC and different relations with PTSD future symptoms, underscoring associations with the anterior and posterior hippocampus. These findings enrich our understanding of PTSD pathophysiology and provide support for future investigations of imaging biomarkers predictive of disease progression.

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Preferential recruitment of the basolateral amygdala during memory encoding of negative scenes in posttraumatic stress disorder

Cited by 24 publications

References 55 publications

Susceptibility and Resilience to Posttraumatic Stress Disorder–like Behaviors in Inbred Mice

Susceptibility and Resilience to Posttraumatic Stress Disorder–like Behaviors in Inbred Mice

The association of PTSD symptom severity with amygdala nuclei volumes in traumatized youths

Functional connectivity of hippocampal subregions in PTSD: relations with symptoms

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