2023-08-17 ペンシルベニア州立大学(PennState)
◆この研究は、脳の前頭前野が計画、記憶、意思決定、社会的行動などのエグゼクティブ機能に関連すると考えられる部位でのソマトスタチンのシグナル機構を説明しています。この研究は、人間の脳でのソマトスタチンの機能と、そのシグナルがいくつかの神経精神疾患でどのように間違っているかを解明するための初期段階です。
<関連情報>
- https://www.psu.edu/news/eberly-college-science/story/uncovering-role-somatostatin-signaling-brain/
- https://www.cell.com/cell-reports/fulltext/S2211-1247(23)00987-7
ソマトスタチンペプチドシグナル伝達は皮質回路を減衰させ、探索行動を促進する Somatostatin peptide signaling dampens cortical circuits and promotes exploratory behavior
Dakota F. Brockway,Keith R. Griffith,Chloe M. Aloimonos,Thomas T. Clarity,J. Brody Moyer,Grace C. Smith,Nigel C. Dao,Md Shakhawat Hossain,Patrick J. Drew,Joshua A. Gordon,David A. Kupferschmidt,Nicole A. Crowley
Cell Reports Published:August 16, 2023
DOI:https://doi.org/10.1016/j.celrep.2023.112976
Highlights
•SST peptide signaling confers broad inhibitory control in the prefrontal cortex
•Optogenetic activation of SST neurons mimics pharmacological effects of SST
•SST neurons display task-relevant activity during exploratory behaviors in vivo
•Pharmacological administration of SST receptor targeting drugs promotes exploratory behavior
Summary
We sought to characterize the unique role of somatostatin (SST) in the prelimbic (PL) cortex in mice. We performed slice electrophysiology in pyramidal and GABAergic neurons to characterize the pharmacological mechanism of SST signaling and fiber photometry of GCaMP6f fluorescent calcium signals from SST neurons to characterize the activity profile of SST neurons during exploration of an elevated plus maze (EPM) and open field test (OFT). We used local delivery of a broad SST receptor (SSTR) agonist and antagonist to test causal effects of SST signaling. SSTR activation hyperpolarizes layer 2/3 pyramidal neurons, an effect that is recapitulated with optogenetic stimulation of SST neurons. SST neurons in PL are activated during EPM and OFT exploration, and SSTR agonist administration directly into the PL enhances open arm exploration in the EPM. This work describes a broad ability for SST peptide signaling to modulate microcircuits within the prefrontal cortex and related exploratory behaviors.
