過剰な不安を抑える脳のセーフティネット~不安誘発的な環境で活性化する神経回路を発見~

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2025-03-31 理化学研究所

理化学研究所の研究チームは、不安を誘発する環境下で活性化し、不安様行動を抑制する神経回路をマウス実験で発見。内側手綱核上部亜核から脚間核外側亜核外側領域への神経投射が鍵で、後者の神経細胞を活性化すると不安様行動が減少し、抑制すると増加することが確認された。不安環境下ではこの神経活動が自然に高まることも判明。この神経回路は不安過剰を抑える「脳内セーフティネット」として機能する可能性がある。

<関連情報>

内側手綱核の上側部分から間脳核への神経経路が不安を抑制する The neural pathway from the superior subpart of the medial habenula to the interpeduncular nucleus suppresses anxiety

Takehisa Handa,Taku Sugiyama,Tanvir Islam,Joshua P. Johansen,Yuchio Yanagawa,Thomas J. McHugh & Hitoshi Okamoto
Molecular Psychiatry  Published:26 March 2025
DOI:https://doi.org/10.1038/s41380-025-02964-8

過剰な不安を抑える脳のセーフティネット~不安誘発的な環境で活性化する神経回路を発見~

Abstract

The medial habenula (MHb) and its projection target, the interpeduncular nucleus (IPN), are highly conserved throughout vertebrate evolution. The MHb-IPN pathway connects the limbic system to the brainstem, consisting of subpathways that project in a topographically organized manner, and has been implicated in the regulation of fear and anxiety. Previous studies have revealed subregion-specific functions of the cholinergic ventral MHb and a substance P (SP)-positive (SP+) subpart of the dorsal MHb (dMHb). In contrast, the dMHb also contains another subpart, a SP-negative subpart known as the ‘superior part of MHb (MHbS)’. Although the MHbS has been characterized from various aspects, e.g. distinct c-Fos responses to stressful events and electrophysiological properties compared to other subregions, many of its physiological functions remain to be investigated. Here we found that dopamine receptor D3 (DRD3)-Cre mice enable the labeling of the IPN subregion that receives the MHbS projection. The Cre-expressing somata within the lateral subnucleus of the IPN (LIPN) were concentrated in its most lateral area, which we refer to as the ‘lateral subregion of the LIPN (lLIPN)’. This region is characterized by the absence of SP+ axons, in contrast to the medial subregion of the LIPN (mLIPN) innervated by the SP+ axons from the dorsal MHb. Chemogenetic activation and genetically induced synaptic silencing of the DRD3-Cre+ cells reduced and enhanced anxiety-like behavior, respectively. Moreover, c-Fos expression was increased in the lLIPN under an anxiogenic environment. These findings suggest that the MHbS-lLIPN pathway is activated under anxiogenic environments to counteract anxiety.

生物工学一般
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