Astrocytic NO drives presynaptic cascade for inducing ischemic longterm potentiation at hippocampal CA1 synapses

2021 Fiscal Year Annual Research Report

• Project/Area Number: 20K16509
• Research Institution: Okinawa Institute of Science and Technology Graduate University
• Principal Investigator: WANG Han・Ying 沖縄科学技術大学院大学, 細胞分子シナプス機能ユニット, ポストドクトラルスカラー (70814333)
• Project Period (FY): 2020-04-01 – 2022-03-31
• Keywords: Anoxia / LTP / Glutamate / NO / Hippocampus

Outline of Annual Research Achievements

A transient anoxia can be mimicked in slices as anoxia-induced long-term potentiation (aLTP) of glutamate release. Although nitric oxide (NO) is responsible for aLTP induction, the site of NO production is unclear as well as the mechanism by which aLTP is expressed and maintained for a long period.
We identified that NO is released from both pyramidal neurons and nearby astrocytes. We also found that elevated NO switches on a positive feedback loop for its regenerative production. Once aLTP is expressed, it occludes activity-dependent LTP, which however can be rescued by blocking the regenerative loop of NO production.
These results offer a therapeutic possibility of rescuing patients from memory deficit after exposure to anoxia.