Pde4b-regulated cAMP signaling pathway in the AUDGABA-S1TrSst circuit underlies acute stress-induced anxiety-like behavior
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PROVIDER: PRJNA1205373 | ENA |
REPOSITORIES: ENA
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Project description:Pde4b-regulated cAMP signaling pathway in the AUDGABA-S1TrSst circuit underlies acute stress-induced anxiety-like behavior
| PRJNA1204092 | ENA
Project description:Acute stress-induced anxiety is an important way for animals to avoid danger. However, neural and molecular mechanisms that underlie control of anxiety behavior are largely elusive. Here, we find acute physical stress activates a large number of neurons in the primary somatosensory cortex, trunk region (S1Tr). Single-cell sequencing reveals the S1Tr c-fos positive neurons activated by acute stress are largely GABAergic somatostatin (Sst) neurons. These S1TrSst neurons activated by acute stress showed desensitization during subsequent anxiety-like behavior tests. Selective inhibition or apoptosis of S1TrSst neurons mimics acute stress effects to induce anxiety. In contrast, selective activation of S1TrSst neurons reduced acute stress-induced anxiety. Furthermore, we demonstrate that S1TrSst cells receive inputs from the secondary auditory cortex, dorsal area (AUD) GABAergic neurons to modulate acute stress-induced anxiety. Finally, from the results of spatial transcriptome sequencing and precise projection-specificity Pde4b protein knockdown strategy, we show that acute stress reduces Pde4b-regulated cyclic adenosine monophosphate (cAMP) signaling pathway activity in the AUDGABA-S1TrSst projections and resulting in a hypoactivity of S1TrSst neurons during subsequent behavioral tests. Our study unveils a neural and molecular mechanism for acute stress-elicited anxiety and affords a theoretical basis for clinical treatment of anxiety disorders.
2025-01-03 | GSE285650 | GEO
Project description:Acute stress-induced anxiety is an important way for animals to avoid danger. However, neural and molecular mechanisms that underlie control of anxiety behavior are largely elusive. Here, we find acute physical stress activates a large number of neurons in the primary somatosensory cortex, trunk region (S1Tr). Single-cell sequencing reveals the S1Tr c-fos positive neurons activated by acute stress are largely GABAergic somatostatin (Sst) neurons. These S1TrSst neurons activated by acute stress showed desensitization during subsequent anxiety-like behavior tests. Selective inhibition or apoptosis of S1TrSst neurons mimics acute stress effects to induce anxiety. In contrast, selective activation of S1TrSst neurons reduced acute stress-induced anxiety. Furthermore, we demonstrate that S1TrSst cells receive inputs from the secondary auditory cortex, dorsal area (AUD) GABAergic neurons to modulate acute stress-induced anxiety. Finally, from the results of spatial transcriptome sequencing and precise projection-specificity Pde4b protein knockdown strategy, we show that acute stress reduces Pde4b-regulated cyclic adenosine monophosphate (cAMP) signaling pathway activity in the AUDGABA-S1TrSst projections and resulting in a hypoactivity of S1TrSst neurons during subsequent behavioral tests. Our study unveils a neural and molecular mechanism for acute stress-elicited anxiety and affords a theoretical basis for clinical treatment of anxiety disorders.
2025-01-02 | GSE285495 | GEO
Project description:Both the amygdala and the bed nucleus of the stria terminalis (BNST) have been implicated in maladaptive anxiety characteristic of anxiety disorders. However, the underlying circuit and cellular mechanisms have remained elusive. Here we show that mice with Erbb4 gene deficiency in somatostatin-expressing (SOM+) neurons exhibit heightened anxiety as measured in the elevated plus maze test and the open field test, two assays commonly used to assess anxiety-related behaviors in rodents. Using a combination of electrophysiological, molecular, genetic and pharmacological techniques we demonstrate that the abnormal anxiety in the mutant mice is caused by enhanced excitatory synaptic inputs onto SOM+ neurons in the central amygdala (CeA), and the resulting reduction in inhibition onto downstream SOM+ neurons in the BNST. Notably, our results indicate that an increase in dynorphin signaling in SOM+ CeA neurons mediates the paradoxical reduction in inhibition onto SOM+ BNST neurons, and that the consequent enhanced activity of SOM+ BNST neurons is both necessary for and sufficient to drive the elevated anxiety. Finally, we show that the elevated anxiety and the associated synaptic dysfunctions and increased dynorphin signaling in the CeA-BNST circuit of the Erbb4 mutant mice can be recapitulated by stress in wild-type mice. Together, our results unravel previously unknown circuit and cellular processes in the central extended amygdala that can cause maladaptive anxiety.
2018-05-31 | GSE113979 | GEO
Project description:A central extended amygdala circuit that modulates anxiety
| PRJNA454720 | ENA
Project description:SMC3 is a chromatin binding factor that plays central roles in genome organization and in proper neurodevelopment. Mutations in SMC3 gene (SMC3) induce neurodevelopmental and behavioral phenotypes in humans, including changes in anxiety behavior and self-injury. However, it is not clear what are the exact roles of SMC3 in behavior in adulthood or if its effects are only developmental. Using an adulthood forebrain excitatory neuron specific Smc3 knockout mouse model, the current study determined specific sex-dependent effects of SMC3 ablation during the adulthood. Behavioral tests identified anxiolytic effects of Smc3 knockout in females and anxiogenic effects in males four weeks after initiation of adulthood knockout. The prefrontal cortex, a regulator of anxiety behavior, also displayed sex-dependent effects in dendritic complexity. Transcriptional analysis revealed differential effects of Smc3 knockout in males and females, including changes in anxiety-related genes and relevant transcriptional pathways. While anxiety behavior was sex-specific, both males and females developed self-injury behavior at approximately ten weeks after induction of knockout. The current study demonstrates that neuronal SMC3 regulates anxiety during the adulthood in a sex-specific manner.
2024-09-01 | GSE270835 | GEO
Project description:Investigating the molecular basis and correlates of anxiety-related and depression-like behaviors, we generated a mouse model consisting of high (HAB) and low (LAB) anxiety-related behavior mice. We utilized the elevated plus-maze for testing the genetic predisposition to anxiety-related behavior and, consequently, used this as selection criterion for the inbreeding of our animals. In depression-related tests, HAB mice display a more passive, depression-like coping strategy than LAB mice, resembling clinical comorbidity of anxiety and depression as observed in psychiatric patients. Using a microarray approach, the hypothalamic paraventricular nucleus (PVN), the basolateral/lateral (BLA), the medial (MeA) and central amygdala (CeA), the nucleus accumbens (NAc), the cingulate cortex (Cg) and the supraoptic nucleus (SON) – centers of the central nervous anxiety and fear circuitries – were investigated and screened for differences between HAB and LAB mice. Analysis was performed from six animals per line (HAB and LAB, respectively) pooled per brain region in ten technical replicates, thereof five with a dye-swapped design giving a total of 70 array slides analyzed. The LAB mouse line is referred to as reference.
2011-08-29 | E-GEOD-28999 | biostudies-arrayexpress
Project description:Investigating the molecular basis and correlates of anxiety-related and depression-like behaviors, we generated a mouse model consisting of high (HAB), normal (NAB) and low (LAB) anxiety-related behavior mice. We utilized the elevated plus-maze for testing the genetic predisposition to anxiety-related behavior and, consequently, used this as selection criterion for the inbreeding of our animals. In depression-related tests, HAB mice display a more passive, depression-like coping strategy than LAB mice, resembling clinical comorbidity of anxiety and depression as observed in psychiatric patients. Using a microarray approach, the hypothalamic paraventricular nucleus (PVN), the basolateral (BLA) and central amygdala (CeA), the cingulate cortex (Cg) and the dentate gyrus (DG) – centers of the central nervous anxiety and fear circuitries – were investigated and screened for differences between HAB, NAB and LAB mice. Analysis was performed from four to six animals per line (HAB, NAB and LAB from generation 25, respectively) per brain region, giving a total of 78 individual arrays analyzed. The LAB mouse line is referred to as reference.
2011-05-04 | E-GEOD-29014 | biostudies-arrayexpress
Project description:MAP kinase signaling has been implicated in brain development, long-term memory, and the response to antidepressants. Inducible Braf knockout mice enabled us to unravel a new role of neuronal MAPK signaling for emotional behavior. Braf mice that were induced during adulthood showed normal anxiety but increased depression-like behavior, in accordance with pharmacological findings. In contrast, the inactivation of Braf in the juvenile brain leads to normal depression-like behavior but decreased anxiety in adults. In these mutants we found no alteration of GABAergic neurotransmission but reduced neuronal arborization in the dentate gyrus. Analysis of gene expression in the hippocampus revealed nine downregulated MAPK target genes that represent candidates to cause the mutant phenotype. Our results reveal the differential function of MAPK signaling in juvenile and adult life phases and emphasize the early postnatal period as critical for the determination of anxiety in adults. Moreover, these results validate inducible gene inactivation as new valuable approach, allowing to discriminate between gene function in the adult and the developing postnatal brain. Five male Braf-cko, six male homozygous Braf-flox littermates, six male heterozygous CamkII-Cre, and six male wildtype littermates were killed with CO2, the complete hippocampal tissue was prepared, and total RNA was extracted with the Trizol protocol. The integrity and quality of the RNA samples were analyzed with an RNA electrophoresis chip (RNA 6000 Nano Kit, Agilent, Boeblingen, Germany). RNA samples of high integrity and quality (RIN ≥ 7.5) were further processed with the TotalPrep RNA Amplification Kit (Ambion, Austin, TX, USA) and hybridized onto MouseWG-6 v1.1 Expression Bead-Chips (Illumina, San Diego, CA, USA) following manufacturer’s instructions. Data were analyzed using the software R (used packages: beadarray, limma, and vsn).
2012-04-18 | E-GEOD-33618 | biostudies-arrayexpress
Project description:Embryonic exposure to the endocrine disruptor vinclozolin during gonadal sex determination promotes an epigenetic reprogramming of the male germ-line that is associated with transgenerational adult onset disease states. Further analysis of this transgenerational phenotype on the brain demonstrated reproducible changes in the brain transcriptome three generations (F3) removed from the exposure. The transgenerational alterations in the male and female brain transcriptomes were distinct. In the males, the expression of 92 genes in the hippocampus and 276 genes in the amygdala were transgenerationally altered. In the females, the expression of 1,301 genes in the hippocampus and 172 genes in the amygdala were transgenerationally altered. Analysis of specific gene sets demonstrated that several brain signaling pathways were influenced including those involved in axon guidance and long-term potentiation. An investigation of behavior demonstrated that the vinclozolin F3 generation males had a decrease in anxiety-like behavior, while the females had an increase in anxiety-like behavior. These observations demonstrate that an embryonic exposure to an environmental compound appears to promote a reprogramming of brain development that correlates with transgenerational sex-specific alterations in the brain transcriptomes and behavior. Observations are discussed in regards to environmental and transgenerational influences on the etiology of brain disease. Keywords: expression analysis, transgenerational changes due to vinclozolin
2009-01-03 | GSE14269 | GEO