Pde4b-regulated cAMP signaling pathway in the AUDGABA-S1TrSst circuit underlies acute stress-induced anxiety-like behavior

ABSTRACT: 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE285495 | GEO | 2025/01/02

REPOSITORIES: GEO