2020 Fiscal Year Research-status Report
Astrocytic NO drives presynaptic cascade for inducing ischemic longterm potentiation at hippocampal CA1 synapses
| Project/Area Number |
20K16509
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| Research Institution | Okinawa Institute of Science and Technology Graduate University |
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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, 研究員 (70814333)
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| Project Period (FY) |
2020-04-01 – 2022-03-31
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| Keywords | anoxia / aLTP / Nitric oxide / positive feedback loop / memory |
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| Outline of Annual Research Achievements |
After a stroke, neurons in hippocampal CA1 area are selectively damaged by the toxicity of glutamate leaking out of cells and released from nerve terminals. This is modelled in slices as aLTP of glutamatergic transmission.
Although NO is involved in aLTP induction, neither the origin of NO nor the mechanism of aLTP expression is identified. Our results revealed that NO derived from both neurons and astrocytes induces aLTP, and that aLTP expression is maintained by a positive feedback loop involving NO related cascade molecules.
We also demonstrated that pharmacological block of aLTP expression rescues activity-dependent postsynaptic LTP from occlusive block with aLTP, suggesting an option for rescuing memory impairments and neuronal loss in patients exposed to a transient brain ischemia.
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| Current Status of Research Progress |
Current Status of Research Progress
1: Research has progressed more than it was originally planned.
Reason
My initial project is for 3-years studies but the overall progress of my project is more than my expectation. I introduced some of nice quality instruments for my experiment and animal breeding is going very smoothly as well; all of these speed up my progress.
I always struggled by out-of-date instruments such as micromanipulators and low-resolution fluorescence camera all of which impeded my experiment. Moreover, data obtaining from these obsolete rigs are unstable and unreliable. After importing new micromanipulators and a high-resolution camera, I could record very stable electrophysiological and imaging data to support my idea and hypothesis.
I have accomplished almost 85% of total progress. I'm now going to make figures and manuscript for the submission.
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| Strategy for Future Research Activity |
I've finishing almost 90% of my experiments including:
1. A transient anoxia induces LTP associated with an increased transmitter release probability. 2. Induction of aLTP is mediated by NO and its downstream molecular cascade. 3. Source of NO released from neurons (nNOS) and glia (eNOS) in response to a transient anoxia. 4. NO and its downstream molecular cascade involve in aLTP maintenance. 5. aLTP occludes theta-burst stimulation-induced LTP. 6. Theta-burst stimulation-induced LTP can be rescued by blocking aLTP.
My further plans for this project are remaining as fllows:
1. To analyze two-photon calcium imaging in astrocytes after aLTP induction.
2. To prepare the manuscript and figures for the journal submission.
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| Causes of Carryover |
I am going to the remaining amount for imaging analyzing software and for paper submission.
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