Investigation of the stress-induced synaptic changes and its molecular mechanism in the anterior cingulate cortex

• Project/Area Number: 16K08528
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Environmental physiology(including physical medicine and nutritional physiology)
• Research Institution: Saitama Medical University
• Principal Investigator: Yasushi Hojo 埼玉医科大学, 医学部, 助教 (20536875)
• Project Period (FY): 2016-10-21 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 帯状回 / ストレス / グルココルチコイド受容体 / オシレーション / ドーパミン受容体 / シナプス / グルココルチコイド

Outline of Final Research Achievements

The anterior cingulate cortex (ACC), which is responsible for higher order process including attention, empathy and decision making, is vulnerable to stress. In the ACC, however, the site of action of glucocorticoid, released from adrenal upon stress, remains unclear. We identified the cell type which expresses glucocorticoid receptor in mouse ACC, i.e., glutametargic and GABAergic (parvalbumin- and somatostatin-positive) neurons. Neural circuits of these neurons mainly play a role in generating network oscillation which is associated with the higher order process in ACC above. We also investigated the effect of glucocorticoid on the network oscillation by using the mouse ACC slice. In glucocorticoid-treated group, the magnitude of dopamine-induced modulatory effect on oscillation power was suppressed, suggesting that glucocorticoid alters ACC function via dopaminergic system in ACC.

Academic Significance and Societal Importance of the Research Achievements

ストレスに対して影響を受けやすいと言われていた前部帯状回において、ストレス時に分泌されるホルモンがどの種類の細胞に作用するかを明らかにした点、また、注意・共感・意思決定といった高次脳機能を発揮する際に観測される神経回路の発振現象が、このストレスホルモンによって変化することを明らかにした点。以上二点から、前部帯状回の高次機能がストレスによってどのように変化させられるのか、その解明につながることが期待される。

Research Products

• [Journal Article] Chronic Restraint Stress Affects Network Oscillations in the Anterior Cingulate Cortex in Mice (2020)
  • Author(s): Ito Rina、Nakano Takanari、Hojo Yasushi、Hashizume Miki、Koshiba Mamiko、Murakoshi Takayuki
  • Journal Title: Neuroscience Volume: 437 Pages: 172-183
  • DOI: 10.1016/j.neuroscience.2020.04.021
  • Peer Reviewed
• [Presentation] Identification of cell types that express glucocorticoid receptors in mouse anterior cingulate cortex (2019)
  • Author(s): Yasushi Hojo, Mai Kawata, Rina Ito,Miki Hashizume,Takanari Nakano, Takayuki Murakoshi
  • Organizer: The 42nd annual meeting of the Japan Neuroscience Society
• [Presentation] The effect of glucocorticoid on dopamine receptors in the anterior cingulate cortex of mice (2018)
  • Author(s): Hojo, Y., Matsunaga, T., Komatsu, M., Ito K., Hashimoto T., Takizawa, K., Noguchi S., Ito, R., Hashizume, M., Nakano, T. & Murakoshi, T.
  • Organizer: 日本神経科学会
• [Presentation] Effects of glucocorticoid on pre-pulse inhibition and network oscillation in anterior cingulate cortex in mice (2017)
  • Author(s): 松永洸昴、小松睦実、伊藤健治、瀧澤恵子、伊藤吏那、中野貴成、北條泰嗣、村越隆之
  • Organizer: 第90回日本薬理学会年会
  • Place of Presentation: 長崎ブリックホール
  • Year and Date: 2017-03-15
• [Presentation] プレパルス抑制（PPI）と前部帯状回皮質（ACC)神経回路オシレーションに対するグルココルチコイド投与の影響 (2017)
  • Author(s): 松永洸昴、小松睦実、伊藤健治、瀧澤恵子、伊藤吏那、中野貴成、北條泰嗣、村越隆之
  • Organizer: 第26回神経行動薬理若手研究者の集い
  • Place of Presentation: 福岡大学
  • Year and Date: 2017-03-14
• [Presentation] Effect of glucocorticoid on prepulse inhibition and network oscillation in the anterior cingulate cortex of mice (2017)
  • Author(s): Hojo, Y., Matsunaga, T., Komatsu, M., Ito K., Takizawa, K., Ito, R., Hashizume, M., Nakano, T. & Murakoshi, T.
  • Organizer: 日本神経科学会