Distinct reward processing by subregions of the nucleus accumbens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA918789 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR22993476_1.fastq.gz | Fastqsanger.gz | |||
| SRR22993476_2.fastq.gz | Fastqsanger.gz | |||
| SRR22993477_1.fastq.gz | Fastqsanger.gz | |||
| SRR22993477_2.fastq.gz | Fastqsanger.gz | |||
| SRR22993478_1.fastq.gz | Fastqsanger.gz |
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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
Project description:Whilst reward pathologies e.g., anhedonia and apathy, are major and common in stress-related neuropsychiatric disorders, their neurobiological bases and therefore treatment are poorly understood. Functional imaging studies in humans with reward pathology indicate that attenuated BOLD activity in nucleus accumbens (NAc) occurs during reward anticipation/expectancy but not reinforcement; potentially, this is dopamine (DA) related. In mice, chronic social stress (CSS) leads to reduced reward learning and effortful motivation and, here, DA-sensor fibre photometry was used to investigate whether these behavioural deficits co-occur with altered NAc DA activity during reward anticipation and/or reinforcement. In CSS mice relative to controls: (1) Reduced discriminative learning of the sequence, tone-on + appetitive behaviour = tone-on + sucrose reinforcement, co-occurred with attenuated NAc DA activity throughout tone-on and sucrose reinforcement. (2) Reduced effortful motivation during the sequence, operant behaviour = tone-on + sucrose delivery + tone-off / appetitive behaviour = sucrose reinforcement, co-occurred with attenuated NAc DA activity at tone-on and typical activity at sucrose reinforcement. (3) Reduced effortful motivation during the sequence, operant behaviour = appetitive behaviour + sociosexual reinforcement co-occurred with typical NAc DA activity at female reinforcement. Therefore, in CSS mice attenuated NAc DA activity is specific to reward anticipation and as such potentially causal to deficits in learning and motivation. CSS did not impact on the transcriptome of ventral tegmentum DA neurons, suggesting that its stimulus-specific effects on NAc DA activity originate elsewhere in the neural circuitry of reward processing.
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Project description:ATP-dependent chromatin remodeling proteins are being implicated increasingly in the regulation of complex behaviors, including models of several psychiatric disorders. Here, we demonstrate that Baz1b, an accessory subunit of the ISWI family of chromatin remodeling complexes, is upregulated in the nucleus accumbens (NAc), a key brain reward region, in both chronic cocaine-treated mice and mice that are resilient to chronic social defeat stress. In contrast, no regulation is seen in mice that are susceptible to this chronic stress. Viral-mediated overexpression of Baz1b, along with its associated subunit Smarca5, in mouse NAc is sufficient to potentiate both rewarding responses to cocaine, including cocaine self-administration, and resilience to chronic social defeat stress. However, despite these similar, proreward behavioral effects, genome-wide mapping of BAZ1B in NAc revealed mostly distinct subsets of genes regulated by these chromatin remodeling proteins after chronic exposure to either cocaine or social stress. Together, these findings suggest important roles for BAZ1B and its associated chromatin remodeling complexes in NAc in the regulation of reward behaviors to distinct emotional stimuli and highlight the stimulus-specific nature of the actions of these regulatory proteins. BAZ1B (WSTF) ChIP-seq of mouse. Cocaine vs Saline, 3 biological replicates. In social defeat model: Normal control vs Susceptible vs Resilient, 3 biological replicates.
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Project description:Nuclear receptor subfamily 1, group D, member 1 (Nr1d1) (also known as Rev-erb alpha) has been linked to circadian rhythm regulation, mood-related behavior, and disorders associated with social deficits. Recent work from our laboratory found striking decreases in Nr1d1 in nucleus accumbens (NAc) in the maternal condition and indirect evidence that Nr1d1 was interacting with numerous addiction and reward-related genes to modulate social reward. In this study, we applied our insights from the maternal state to non-parental adult mice to determine whether decreases in Nr1d1 expression in NAc via adeno-associated viral (AAV) vectors and short hairpin RNA (shRNA)-mediated gene knockdown were sufficient to modulate social reward and mood-related behaviors. We also used microarray analysis of to identify gene expression alterations induced by the lowering of Nr1d1 expression. We used microarrays to evalute the effects of knockdown of mRNA for Nr1d1 in nuclues accumbens on gene expression.
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Project description:A substantial proportion of basal amygdala (BA) glutamate neurons project to nucleus accumbens (NAc). The evidence that these neurons are activated by reward and/or aversion is equivocal. Social stimuli are highly salient, and in male mice we conducted a detailed analysis of the responsiveness of BA-NAc neurons to estrous female (social reward, SR) or aggressive male (social aversion, SA). Both SR and SA activated c-Fos expression in a relatively high number of BA-NAc neurons in intermediate (int) BA. Using Fos-TRAP2 mice, the majority of social int-BA-NAc neurons were activated by either SR or SA, i.e. were monovalent, and in similar numbers. Fiber photometry provided corroborative evidence that int-BA-NAc neural pathway activity was similar in response to SR or SA. These findings contribute substantially to understanding the topography and valence-specificity of BA-NAc neurons with respect to highly salient stimuli, and to identifying molecular targets for treatment of reward- or aversion-specific psychopathologies.
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Project description:Purpose: The goal of this study to examine mRNA transcriptomic changes in reward-related brain regions of subjects with alcohol use disorder. Methods: Total RNAs were extracted from postmortem nucleus accumbens of 12 AUD and 12 control subjects. rRNA depletion RNA sequencing was performed and the sequence reads were processed using the bulk RNA-seq processing pipeline Pipeliner workflow (Federico et al. Front Genet 2019; 10, 614). AUD-associated mRNA transcriptomic changes were analyzed by the Limma-Voom method. Results: Differentially expressed mRNAs (absolute FC>2.0 & P<0.05) were identified in postmortem nucleus accumbens of subjects with alcohol use disorder (AUD). Chronic alcohol consumption may alter mRNA transcriptome profiles in reward-related brain regions, resulting in alcohol-induced neuroadaptations.
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Project description:Motherhood involves a switch in natural rewards, whereby offspring become highly rewarding. Nucleus accumbens (NAC) is a key CNS region for natural rewards and addictions, but to date no study has evaluated on a large scale the events in NAC that underlie the maternal change in natural rewards. In this study we utilized microarray and bioinformatics approaches to evaluate postpartum NAC gene expression changes in mice. Modular Single-set Enrichment Test (MSET) indicated that postpartum (relative to virgin) NAC gene expression profile was significantly enriched for genes related to addiction and reward in 5 of 5 independently curated databases (e.g., Malacards, Phenopedia). Over 100 addiction/reward related genes were identified and these included: Per1, Per2, Arc, Homer2, Creb1, Grm3, Fosb, Gabrb3, Adra2a, Ntrk2, Cry1, Penk, Cartpt, Adcy1, Npy1r, Htr1a, Drd1a, Gria1, and Pdyn. ToppCluster analysis found maternal NAC expression profile to be significantly enriched for genes related to the drug action of nicotine, ketamine, and dronabinol. Pathway analysis indicated postpartum NAC as enriched for RNA processing, CNS development/differentiation, and transcriptional regulation. Weighted Gene Coexpression Network Analysis identified possible networks for transcription factors, including Nr1d1, Per2, Fosb, Egr1, and Nr4a1. The postpartum state involves increased risk for mental health disorders and MSET analysis indicated postpartum NAC to be enriched for genes related to depression, bipolar disorder, and schizophrenia. Mental health related genes included: Fabp7, Grm3, Penk, and Nr1d1. We confirmed via quantitative PCR Nr1d1, Per2, Grm3, Penk, Drd1a, and Pdyn. This study indicates for the first time that postpartum NAC involves large scale gene expression alterations linked to addiction and reward. Because the postpartum state also involves decreased response to drugs, the findings could provide insights into how to mitigate addictions.
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Project description:The nucleus accumbens plays a central role in ther regulation of reward, emotion, motivation and goal-directed behavior. Gene expression impairments in this brain region are of crucial interest to understand the neurobiological underpinnings of heroin use disorder. We used the Affymetrix HG-U133A microarray to assess gene expression in the post-mortem nucleus accumbens of human heroin users and control subjects and identified differentially expressed genes.
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Project description:To better understand the transcriptome of Nucleus Accumbens (NAc) – a key brain reward region – under chronic cocaine treatment, we perform the first Iso-Seq analysis on its mRNAs to determine the full-length transcripts without assembly.
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