Pde4b-regulated cAMP signaling pathway in the AUDGABA-S1TrSst circuit underlies acute stress-induced anxiety-like behavior
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ABSTRACT:
PROVIDER: PRJNA1205373 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR31866652_1.fastq.gz | Fastqsanger.gz | |||
| SRR31866652_2.fastq.gz | Fastqsanger.gz |
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Project description:Pde4b-regulated cAMP signaling pathway in the AUDGABA-S1TrSst circuit underlies acute stress-induced anxiety-like behavior
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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.
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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.
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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.
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