Higher-Order Olfactory Threat Associations in the Amygdala-Posterior Piriform Cortex Network
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PROVIDER: PRJNA1180627 | ENA |
REPOSITORIES: ENA
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Project description:Fear, while crucial for survival, is a component of a myriad of psychiatric illnesses in its extreme. Persistent fear memories can form through processes such as second-order conditioning (SOC), during which a second-order conditioned stimulus (CS2) acquires significance by associating with a first-order conditioned stimulus (CS1). The neural circuitry underlying SOC, particularly the roles of sensory cortices, remains poorly understood. We explored the mechanisms of olfactory SOC in rats, focusing on the basolateral amygdala (BLA) and posterior piriform cortex (pPC). Our results demonstrate that NMDAR-dependent plasticity in both regions is essential for SOC. The BLA mediates the CS2-CS1 association, while the pPC, receiving inputs from the locus coeruleus and BLA, is critical for memory encoding and retrieval. Transcriptomic analysis of Fos+ ensembles in the two structures shows distinct gene activation in excitatory neurons, highlighting key pathways involved in learning and memory. These findings highlight the pPC’s role in integrating sensory and affective information, essential for long-term threat memory consolidation.
2025-06-04 | GSE280826 | GEO
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Project description:Dynamic Patterns of Threat-associated Gene Expression in the Amygdala and Blood
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Project description:Purpose: Identification the biological response to fear and stress in both brain and blood is vital for investigators performing peripheral studies of psychiatric traits. The goal of this study was to determine genes responsive to fear conditioning (FC), a well-characterized rodent model of threat-exposure, in the presence or absence of prior stress history, providing insight into the physiological processes underlying traumatic memory formation and trauma-related disorders such as PTSD. Methods: RNA sequencing was performed in blood and amygdala from mice that underwent fear conditioning (FC) with and without prior immobilization stress history (Immo+FC), or untreated animals (home cage HC). Libraries were prepared using the Illumina TruSeq™ RNA kit as per manufacturer’s instructions. Libraries were normalized and 8 samples were multiplexed in each lane of the flowcell. PhiX was used as an internal control on each lane to monitor the error statistics. Cluster generation was performed on the V3 flowcell on the Illumina cBot. The clustered flowcell was then sequenced on the Illumina HiSeq1000 system employing a single-end 101 cycles run. Alignment to the mm10 UCSC Mouse Assembly was performed using STAR version 2.3 (Dobin et al, 2013); parameters were set using the annotation as a splice junction reference. Sample reads were assembled into transcript models using cufflinks (v2.1.1) which were then merged and processed with cuffdiff v2.1.1, (Trapnell et al, 2012) to produce per sample FPKM expression levels and estimate differential expression between the sample groups. Results: In the amygdala, 607 genes associated with FC vs. HC (FDR<.05). In the same tissue, 516 genes showed different expression in response of immobilization (Immo+FC) compared to the FC group (FDR<.05). In the blood of the same animals, 468 genes had distinct changes in expression (Immo+FC vs FC; FDR<.05) and were enriched for biological processes such as inflammation and cytokine signaling. Conclusions: This study identified genes and pathways that respond to threat in the amygdala and blood of animals with and without a prior stress history. Future studies will be needed to examine the necessity, function and relevance of these regulated genes in human clinical stress and trauma-related disorders including.
2018-07-06 | GSE116630 | GEO
Project description:Anxiety is elicited by excessive apprehension about unpredictable threats. However, the neural circuit governing unpredictable threat induced anxiety remains unclear. Here, we found ventral bed nucleus of the stria terminalis (vBNST) GABAergic neurons displayed selective activation to unpredictable threats by means ofthrough coordinated excitatory input from insular cortex (IC) glutamergic neurons and inhibitory input from lateral nucleus of the amygdala (CeL) somatostatin (SOM) neurons. Using activity-dependent neuronal tagging technology, we found that unpredictable threat responsive cells in vBNST drive freezing and anxiety via projections to ventral lateral periaqueductal grey (vlPAG) and median nucleus of the amygdala (CeM) respectively. Finally, we identified KCNQ3 plays an essential role in hyperactivity of vBNST GABAergic neurons and induced anxiety. These data identified a forward inhibitory circuit that determine the selective activation of vBNST in unpredictable threat and anxiety, and suggest that Kcnq3 KCNQ3 channel acts as a promising target in treatment of anxiety disorder following unpredictable stress.
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Project description:To investigate whether male MPN- and VMHvl-projecting neurons in posterior amygdala have distinct transcriptional profiles, we conducted RNAseq onto these subpoplations that were microdissected by laser capture microdissection. Our results demonstrate that each subpoplations had largely distinct set of enriched genes.
2020-06-05 | GSE151798 | GEO
Project description:Transcriptional profiles of male posterior amygdala
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Project description:BackgroundAmygdala-prefrontal cortex (PFC) functional connectivity may be influenced by anxiety and development. A prior study on anxiety found age-specific dysfunction in the ventromedial PFC (vmPFC), but not amygdala, associated with threat-safety discrimination during extinction recall (Britton et al.). However, translational research suggests that amygdala-PFC circuitry mediates responses following learned extinction. Anxiety-related perturbations may emerge in functional connectivity within this circuit during extinction recall tasks. The current report uses data from the prior study to examine how anxiety and development relate to task-dependent amygdala-PFC connectivity.MethodsEighty-two subjects (14 anxious youths, 15 anxious adults, 25 healthy youths, 28 healthy adults) completed an extinction recall task, which directed attention to different aspects of stimuli. Generalized psychophysiological interaction analysis tested whether task-dependent functional connectivity with anatomically defined amygdala seed regions differed across anxiety and age groups.ResultsWhole-brain analyses showed significant interactions of anxiety, age, and attention task (i.e., threat appraisal, explicit threat memory, physical discrimination) on left amygdala functional connectivity with the vmPFC and ventral anterior cingulate cortex (Talairach XYZ coordinates: -16, 31, -6 and 1, 36, -4). During threat appraisal and explicit threat memory (vs. physical discrimination), anxious youth showed more negative amygdala-PFC coupling, whereas anxious adults showed more positive coupling.ConclusionsIn the context of extinction recall, anxious youths and adults manifested opposite directions of amygdala-vmPFC coupling, specifically when appraising and explicitly remembering previously learned threat. Future research on anxiety should consider associations of both development and attention to threat with functional connectivity perturbations.
| S-EPMC5096647 | biostudies-literature
Project description:Piriform cortex were isolated from 12-month old wild type and Q140 knock-in (KI) HD mice. Transcriptomic analysis (RNASeq) was performed on 2 genotypes: WT and Q140, 6 replicates per genotype.
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Project description:19 female mice of the C57BL/6J and B6D2F1N strains were housed in either standard (control) or enriched (including access to playgrounds) conditions. The animals were trained to perform a cognitive judgement bias test. Upon completion of training, the animals underwent the test paradigm and were sacrificed. Anterior and posterior portions of the amygdala were finally dissected for RNA-sequencing.
2022-10-24 | GSE209999 | GEO