Animal model of cognitive impairments following gelastic seizures with the use of optogenetics

• Project/Area Number: 16K15644
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Neurosurgery
• Research Institution: Niigata University
• Principal Investigator: Hasegawa Isao 新潟大学, 医歯学系, 教授 (60282620)
• Co-Investigator(Renkei-kenkyūsha): 岡戸 晴生 (亀山 茂樹) 東京都医学総合研究所 (60221842) ; 目黒 玲子 新潟大学 (30251804) ; 戸田 春男 新潟医療福祉大学 (10217507)
• Research Collaborator: 園田 真樹 新潟大学
• Project Period (FY): 2016-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000); Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 笑い発作 / てんかん性脳症 / 視床下部 / 視床 / 光遺伝学 / チャネルロドプシン / 作業記憶 / 視床下部過誤腫 / 手綱核 / 視床背内側核 / ラット / 動物モデル / 前頭葉 / 脳神経外科学 / 脳・神経

Outline of Final Research Achievements

We introduced ChR2 into lateral hypothalamus using AAV9 viral vectors, and photostimulated ChR2-expressing axonal terminals in the dorsomedial and lateral habenular nuclei in the thalamus at 80 Hz when the rats conducted a spatial working memory and control visual discrimination tasks. The pathway-specific photostimulation induced transient increases and late suppression of δ～β and γ powers, and induced working memory task-specific behavioral impairments when stimulation was applied during the cue-presenting period, but not during the delay period. These results demonstrated the feasibility of pathway-specific photostimulation in mimicking post-epileptic neural circuit changes, indicating that transient hyperactivation and subsequent suppression of the hypothalamus-dorsal thalamic pathway plays a role in cognitive impairments following gelastic seizures.

Research Products

• [Journal Article] Locally induced neuronal synchrony precisely propagates to specific cortical areas without rhythm distortion. (2018)
  • Author(s): Toda H, Kawasaki K, Sato S, Horie M, Nakahara K, Bepari AK, Sawahata H, Suzuki T, Okado H, Takebayashi H, Hasegawa I.
  • Journal Title: Scientific Reports Volume: - Issue: 1 Pages: 7678-7678
  • DOI: 10.1038/s41598-018-26054-8
  • Peer Reviewed / Open Access
• [Journal Article] Predictors of cognitive function in patients with hypothalamic hamartoma following stereotactic radiofrequency thermocoagulation surgery. (2017)
  • Author(s): Sonoda M, Masuda H, Shirozu H, Ito Y, Akazawa K, Asano E, Kameyama S.
  • Journal Title: Epilepsia Volume: 58 Pages: 1556-1565
  • Peer Reviewed
• [Presentation] Predictive analysis of perioperative cognitive function in patients with hypothalamic hamartoma, who underwent surgery of stereotactic radiofrequency thermocoagulation. (2017)
  • Author(s): Sonoda M, Masuda H, Shirozu H, Ito Y, Akazawa K, Kameyama S
  • Organizer: The 11th Asian & Oceanian Epilepsy Congress