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A Circult Mechanism for Differentiating Positive and Negative Associations

ABSTRACT: The ability to differentiate stimuli predicting positive or negative outcomes is critical for survival, and perturbations of emotional processing underlie many psychiatric disease states. Different neuronal populations of the basolateral amygdala complex (BLA) encode fearful or rewarding associations, but the molecular identity of these functionally distinct populations of BLA neurons remained unknown. Here, we show that BLA neurons projecting to the nucleus accumbens (NAc-projectors) or the centromedial amygdala (CeM-projectors) underwent opposing synaptic changes following fear or reward conditioning. The photostimulation of NAc projectors supported positive reinforcement while photostimulation of CeM projectors mediated negative reinforcement. In search of defining molecular characteristics of these functionally-distinct BLA neuronal populations, we compared gene expression profiles of NAc- and CeM-projectors.

ORGANISM(S): Mus musculus

PROVIDER: GSE66345 | GEO | 2015/02/27

SECONDARY ACCESSION(S): PRJNA276574

REPOSITORIES: GEO

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A Circult Mechanism for Differentiating Positive and Negative Associations

Project description:The ability to differentiate stimuli predicting positive or negative outcomes is critical for survival, and perturbations of emotional processing underlie many psychiatric disease states. Different neuronal populations of the basolateral amygdala complex (BLA) encode fearful or rewarding associations, but the molecular identity of these functionally distinct populations of BLA neurons remained unknown. Here, we show that BLA neurons projecting to the nucleus accumbens (NAc-projectors) or the centromedial amygdala (CeM-projectors) underwent opposing synaptic changes following fear or reward conditioning. The photostimulation of NAc projectors supported positive reinforcement while photostimulation of CeM projectors mediated negative reinforcement. In search of defining molecular characteristics of these functionally-distinct BLA neuronal populations, we compared gene expression profiles of NAc- and CeM-projectors. For comparison of gene expression profiles of NAc- and CeM-projectors, we conducted two independent RNA sequencing experiments. In experiment-1, a total of n=9 samples (n=4 NAc- and n=5 CeM-projectors) are analyzed. In experiment-2, a total of n=8 samples (n=4 NAc- and n=4 CeM-projectors) are analyzed.

2015-02-27 | E-GEOD-66345 | biostudies-arrayexpress

Central amygdala cell types and their transcriptional regulation by fasting

Project description:A complete cell type census based on their full molecular profiles at subclass level and their subnuclei distribution in the central amygdala (CeA), linked with their behavior relevance, is still lacking. Here, we performed single nuclei RNA sequencing in adult mice and compared the results with known genetic and functionally defined populations. We identified 9 transcriptionally and spatially discrete cell types (3 in the lateral division CeL; 5 in the medial division CeM; and 1 in the capsular division CeC). In the CeL, we found one PKCδ expressing cluster (CeL PKCδ ) and two clusters marked by Sst: the CeL Sst cluster which contains the largest and most highly expressing population of Sst-positive neurons, and the CeL NTS/Tac2 cluster which contains low expressing Sst-positive cells. This two Sst population are also Htr2a positive. The CeC contains one cluster marked by the expression of Calcrl and partially expressed PKCδ. In the CeM, the largest cluster was marked by Il1Rapl2, which contains the CeM subsets of Pnoc and Htr2a, and is likely appetitive. Another Sst population, the CeM Tac1/Sst, remains largely unexplored. Moreover, we discovered three previously uncharacterized CeM clusters: CeM Vdr, CeM Drd2/Rai14, and CeM Dlk1. To begin investigating whether these cell types show individual responses in appetitive behavior, we compared their transcriptomes in food-deprived and satiated mice. We found a cell type specific transcriptional response across neuronal populations, particularly in one of the appetitive clusters in the CeL.

2023-05-06 | GSE231790 | GEO

Differential Regulation of Alcohol Consumption and Reward by the Transcription Cofactor LMO4

Project description:The goal of this study is to identify and validate transcriptional targets of LMO4 in the Basolateral Amygdala (BLA) and the Nucleus Accumbens (NAc) We mapped about 15-25 million reads per sample to the mouse genome (mm9) . We identified about 16,000 transcripts per sample.

2020-02-29 | GSE141312 | GEO

Cross-Species Single-cell Comparative Analysis of Amygdala

Project description:The amygdala or amygdala-like structure in the brain are found in all vertebrates, and plays a critical role for emotional processing. But the cellular architecture of amygdala and how they evolved are still elusive. Here, we generated single-nucleus RNA-sequencing data for more than 200,000 cells in human, macaque, mouse and chicken amygdala. Abundant neuronal cell types derived from different subnuclei of amygdala were identified in all datasets. Cross-species analyses revealed GABAergic neurons and GABAergic neuron-enriched subnuclei of amygdala were well-conserved in cellular composition and marker gene expression, whereas glutamatergic neuron-enriched subnuclei were relatively divergent. Furthermore, we discovered that LAMP5+ interneurons were much more numerous in primates, while DRD2+ GABAergic neurons, LAMP5+ and SATB2+ glutamatergic neurons were predominant in the human central amygdalar nucleus (CEA) and basolateral amygdala complex (BLA), respectively. In addition, we also identified GABAergic neuron-enriched subnuclei of amygdala in the chicken. Altogether, our study highlight extremely cell-type diversity in the amygdala across species and their species-specifc adaptations.

2022-12-13 | GSE195445 | GEO

Activity-dependent transcriptional profiling of basolateral amygdala neurons in response to valence-specific stimuli

Project description:Activity-dependent transcriptional profiling was performed in the basolateral amygdala in order to identify unique genetic markers for functionally distinct neuronal populations

2016-10-16 | GSE78137 | GEO

Astrocyte-mediated regulation of BLAWFS1 neurons alleviates risk-assessment deficits in DISC1-N mice

Project description:Assessing and responding to threats is vital in everyday life. Unfortunately, many mental illnesses involve impaired risk assessment, affecting patients, families, and society. The brain processes behind these behaviors are not well understood. We developed a transgenic mouse model (DISC1-N) with a disrupted avoidance response in risky settings. Our study utilized single-nucleus RNA sequencing to uncover a previously undescribed group of glutamatergic neurons in the basolateral amygdala (BLA) marked by WFS1 expression, whose activity is modulated by adjacent astrocytes. These neurons in DISC1-N mice exhibited diminished firing ability and impaired communication with the astrocytes. Remarkably, optogenetic activation of these astrocytes reinstated neuronal excitability via D-serine acting on BLAWFS1 neurons’ NMDA receptors, leading to improved risk-assessment behavior in the DISC1-N mice. Our findings point to BLA astrocytes as a promising target for treating risk assessment dysfunctions in mental disorders.

2024-04-19 | GSE262541 | GEO

The gastrin-releasing peptide regulates stress-enhanced fear and dopamine signaling

Project description:Fear extinction is an adaptive behavioral process critical for organism’s survival, but deficiency in extinction may lead to PTSD. While the amygdala and its neural circuits are critical for fear extinction, the molecular identity and organizational logic of cell types that lie at the core of these circuits remain unclear. Here we report that mice deficient for amygdala-enriched gastrin-releasing peptide gene (Grp-/-) exhibit enhanced neuronal activity in the basolateral amygdala (BLA) and stronger fear conditioning, as well as deficient extinction in stress-enhanced fear learning (SEFL). rAAV2-retro-based tracing combined with visualization of the GFP knocked in the Grp gene showed that BLA receives several GRPergic conditioned stimulus projections: from the indirect auditory thalamus-to-auditory cortex pathway, medial prefrontal cortex, ventral hippocampus and ventral tegmental area. Transcription of dopamine-related genes was decreased in BLA of Grp-/- mice following SEFL extinction recall, suggesting that the GRP may mediate fear extinction regulation by dopamine.

2021-12-01 | GSE164226 | GEO

Gene expression profile of neurons expressing protein kinase C δ (PKCδ) or somatostatin (SST) in the central amygdala (CEA) of mice

Project description:Circuit neuroscience has made great progress by linking neuronal function to marker gene expression, allowing the specific investigation of otherwise indistinguishable neuronal ensembles. Here, we performed next generation sequencing on two functionally and genetically distinct interneuronal populations marked by the expression of protein kinase C δ (PKCδ) or somatostatin (SST) in the central amygdala (CEA) of mice, which are known to play distinct and sometimes opposing roles in emotion processing. Making their gene expression profile known will aid in forming hypotheses of how different neurotransmitters or psychoactive drugs could alter information processing in these neurons.

2018-12-26 | GSE95154 | GEO

Distinct reward processing by subregions of the nucleus accumbens

Project description:The nucleus accumbens (NAc) plays an important role in motivation and reward processing. Recent studies suggest that different NAc subnuclei differentially contribute to reward-related behaviors. However, how reward is encoded in individual NAc neurons remains unclear. Using in vivo single-cell resolution calcium imaging, we discovered diverse patterns of reward encoding in the medial and lateral shell subdivision of the NAc (NAcMed and NAcLat, respectively). Reward consumption increases NAcLat activity but decreases NAcMed activity, albeit with high variability among neurons. The heterogeneity in reward encoding could be attributed to differences in their synaptic inputs and transcriptional profiles. Specific optogenetic activation of Nts-positive neurons in the NAcLat promotes positive reinforcement, while activation of Cartpt-positive neurons in the NAcMed induces behaviour aversion. Collectively, our study reveals organizational and transcriptional differences in NAc subregions, and provides a framework for future dissection of NAc subregions in physiological and pathological conditions.

2023-01-14 | GSE222274 | GEO

Coordinated excitatory and inhibitory circuits governing unpredictable threat induced anxiety

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.

2024-02-19 | GSE255670 | GEO

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