New approach for the study of body temperature regulation using activity control of GABAergic neurons

2011 Fiscal Year Final Research Report

• Project/Area Number: 22790236
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Environmental physiology (including Physical medicine and Nutritional physiology)
• Research Institution: National Institute for Physiological Sciences
• Principal Investigator: YAMANAKA Megumi (MARUYAMA Megumi) 生理学研究所, 発達生理学研究系, 特別協力研究員 (80346379)
• Project Period (FY): 2010 – 2011
• Keywords: GABA作動性神経 / オプトジェネティクス / チャネルロドプシン / 体温調節 / ハロロドプシン / 遺伝子改変マウス

Research Abstract

GABAergic neurons in the hypothalamus play an important role in the regulation of body temperature. In the present research, I generated new transgenic mice in which GABAergic neurons express light activated proteins, such as channelrhodopsin2(ChR2) or Halorhodopsin(Halo) to control the activity of GABAergic neurons. Tetracycline transactivator(tTA) is inserted in the GAD67 gene allele, GAD67-tTA mice. These mice were crossed with TetO ChR2 mice to generate bi-genic mice. In these mice brain, ChR2 expression is observed in the GABA neurons. However, the expression level of ChR2 is too low to control the activity of GABA neurons. This might be caused by neomycin resistant gene cassette located near tTA gene in the GAD67-tTA mice interfered tTA expressin. To remove Neo cassette, these mice were crossed with Cre mice. Then, these mice were crossed with TetO ChR2 mice again. However, expression level of ChR2 was not increased. In future, I will try virus vector instead of transgenic method to introduce ChR2 in GABAergic neurons.