Distinct reward processing by subregions of the nucleus accumbens
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE222274 | GEO | 2023/01/14
REPOSITORIES: GEO
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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.
2023-12-17 | GSE220269 | GEO
Project description:Reduced reward interest/learning and reward-to-effort valuation are distinct, common symptoms in neuropsychiatric disorders for which chronic stress is a major aetiological factor. Pyramidal glutamate neurons in the basal amygdala (BA) project to various brain regions including nucleus accumbens (NAc). The BA-NAc neural pathway is activated by reward and aversion, with many neurons being monovalent. In adult male mice, chronic social stress (CSS) led to both reduced discriminative reward learning (DRL) associated with decreased BA-NAc Ca2+ activity, and reduced sucrose reward-to-effort valuation (REV) associated, in contrast, with increased BA-NAc Ca2+ activity. Chronic tetanus toxin inhibition of BA-NAc neurons replicated the CSS-DRL effect whilst causing only a mild REV reduction, whilst chronic DREADDs activation of BA-NAc neurons replicated the CSS effect on REV without affecting DRL. This study provides novel evidence that chronic stress disruption of reward processing involves the BA-NAc neural pathway; the bi-directional effects implicate activity changes in BA-NAc reward (learning) and aversion (effort) neurons, with the net overall direction of stress-induced change in activity dependent on on-going stimulus processing and behaviour.
2022-12-01 | GSE216588 | GEO
Project description:Reduced reward interest/learning and reward-to-effort valuation are distinct, common symptoms in neuropsychiatric disorders for which chronic stress is a major aetiological factor. Pyramidal glutamate neurons in the basal amygdala (BA) project to various brain regions including nucleus accumbens (NAc). The BA-NAc neural pathway is activated by reward and aversion, with many neurons being monovalent. In adult male mice, chronic social stress (CSS) led to both reduced discriminative reward learning (DRL) associated with decreased BA-NAc Ca2+ activity, and reduced sucrose reward-to-effort valuation (REV) associated, in contrast, with increased BA-NAc Ca2+ activity. Chronic tetanus toxin inhibition of BA-NAc neurons replicated the CSS-DRL effect whilst causing only a mild REV reduction, whilst chronic DREADDs activation of BA-NAc neurons replicated the CSS effect on REV without affecting DRL. This study provides novel evidence that chronic stress disruption of reward processing involves the BA-NAc neural pathway; the bi-directional effects implicate activity changes in BA-NAc reward (learning) and aversion (effort) neurons, with the net overall direction of stress-induced change in activity dependent on on-going stimulus processing and behaviour.
2022-12-01 | GSE216587 | GEO
Project description:The human striatum can be subdivided into the caudate, putamen, and nucleus accumbens (NAc). In mice, this roughly corresponds to the dorsal medial striatum (DMS), dorsal lateral striatum (DLS), and ventral striatum (NAc). Each of these structures have some overlapping and distinct functions related to motor control, cognitive processing, motivation, and reward. Previously, we used a “time-of-death” approach to identify diurnal rhythms in RNA transcripts in these three human striatal subregions. Here, we identify molecular rhythms across similar striatal subregions collected from C57BL/6J mice across 6 times of day and compare results to the human striatum. Pathway analysis indicates a large degree of overlap between species in rhythmic transcripts involved in processes like cellular stress, energy metabolism, and translation. Notably, a striking finding in humans is that small nucleolar RNAs (snoRNAs) and long non-coding RNAs (lncRNAs) are among the most highly rhythmic transcripts in the NAc and this is not conserved in mice, suggesting the rhythmicity of RNA processing in this region could be uniquely human. Furthermore, the peak timing of overlapping rhythmic genes is altered between species, but not consistently in one direction. Taken together, these studies reveal conserved as well as distinct transcriptome rhythms across the human and mouse striatum and are an important step in understanding the normal function of diurnal rhythms in humans and model organisms in these regions and how disruption could lead to pathology.
2024-02-03 | GSE254949 | GEO
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
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.
2015-02-27 | GSE66345 | GEO
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.
2014-12-01 | GSE62258 | GEO
Project description:Background: Psychosis is a defining feature of schizophrenia and highly prevalent in bipolar disorder. Notably, individuals suffering with these illnesses also have major disruptions in sleep and circadian rhythms, and disturbances to sleep and circadian rhythms can precipitate or exacerbate psychotic symptoms. Psychosis is associated with the striatum, though no study to date has directly measured molecular rhythms and determined how they are altered in the striatum of subjects with psychosis. Methods: Here, we perform RNA-sequencing and both differential expression and rhythmicity analyses to investigate diurnal alterations in gene expression in human postmortem striatal subregions (NAc, caudate, and putamen) in subjects with psychosis relative to unaffected comparison subjects. Results: Across regions, we find differential expression of immune-related transcripts and a substantial loss of rhythmicity in core circadian clock genes in subjects with psychosis. In the nucleus accumbens (NAc), mitochondrial-related transcripts have decreased expression in psychosis subjects, but only in those who died at night. Additionally, we find a loss of rhythmicity in small nucleolar RNAs and a gain of rhythmicity in glutamatergic signaling in the NAc of psychosis subjects. Between region comparisons indicate that rhythmicity in the caudate and putamen is far more similar in subjects with psychosis than in matched comparison subjects. Conclusions: Together, these findings reveal differential and rhythmic gene expression differences across the striatum that may contribute to striatal dysfunction and psychosis in psychotic disorders.
2022-08-31 | GSE202537 | GEO
Project description:Despite addiction being one of the most prevalent and debilitating disorders worldwide, effective treatments are lacking. Repeated cocaine exposure induces maladaptive transcriptional regulation within the brainâ??s reward circuitry, such as the nucleus accumbens (NAc), and epigenetic mechanisms, such as histone acetylation or methylation on Lys (K) residues, have been linked to these lasting actions of cocaine. However, in contrast to K methylation, the functional role of histone Arg (R) methylation remains unexplored in addiction models and poorly understood in brain in general. Here we show that protein-R-methyltransferase-6 (PRMT6) and its associated histone mark, asymmetric dimethylation of R2 on histone H3 (H3R2me2a), are decreased in the NAc of mice and rats after repeated cocaine exposure, as well as in the NAc of cocaine-addicted humans. PRMT6 downregulation occurs selectively in NAc medium spiny neurons expressing dopamine D2 receptors (D2-MSNs) and serves to protect against cocaine-induced addictive-like behavioral abnormalities. Using ChIP-seq, we demonstrate that reduced H3R2me2a binding at gene targets in NAc after repeated cocaine is strongly correlated with increased binding of H3K4me3, and identify Src kinase signaling inhibitor 1 (Srcin1 or p140Cap) as a key gene for these chromatin modifications. Cocaine induction of Srcin1 in NAc, which is associated with reduced Src signaling, decreases cocaine reward, the motivation to self administer cocaine, and cocaine-induced changes in NAc MSN dendritic spines. These results suggest that this suppression of Src signaling in NAc D2-MSNs, via PRMT6 and H3R2me2a downregulation, functions as a homeostatic brake to restrain cocaine action, and provide novel candidates for the development of new treatments for cocaine addiction. H3R2me2A ChIP-seq of mouse. Cocaine vs Saline, 3 biological replicates.
2016-08-08 | E-GEOD-85310 | biostudies-arrayexpress
Project description:The striatum in the brain is involved in various behavioral functions, including reward, and disease processes, such as opioid use disorder (OUD). Further understanding of the role of striatal subregions in reward behaviors and their potential associations with OUD requires molecular identification of specific striatal cell types in human brain. The human striatum contains subregions based on different anatomical, functional, and physiological properties, with the dorsal striatum further divided into caudate and putamen. Both caudate and putamen are associated with alterations in reward processing, formation of habits, and development of negative affect states in OUD. Using single nuclei RNA-sequencing of human postmortem caudate and putamen, we identified canonical neuronal cell types in striatum (e.g., dopamine receptor 1 or 2 expressing neurons, D1 or D2) and less abundant subpopulations, including D1/D2 hybrid neurons and multiple classes of interneurons. By comparing unaffected subjects to subjects with OUD, we found neuronal-specific differences in pathways related to neurodegeneration, interferon response, and DNA damage. DNA damage markers were also elevated in striatal neurons of rhesus macaques following chronic opioid administration. We identified sex-dependent differences in the expression of stress-induced transcripts (e.g., FKBP5) among astrocytes and oligodendrocytes from female subjects with OUD. Thus, we describe striatal cell types and leverage these data to gain insights into molecular alterations in human striatum associated with opioid addiction.
2023-11-28 | GSE233279 | GEO