2016 Fiscal Year Annual Research Report
Risk of hypothermia for memory function
Publicly Offered Research
| Project Area | "LIVING IN SPACE" - Integral Understanding of life-regulation mechanism from "SPACE" |
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| Project/Area Number |
16H01629
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| Research Institution | University of Tsukuba |
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Principal Investigator |
ラザルス ミハエル 筑波大学, 国際統合睡眠医科学研究機構, 准教授 (80469650)
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| Project Period (FY) |
2016-04-01 – 2018-03-31
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| Keywords | 低体温状態 / 記憶固定 / 薬理遺伝学 |
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| Outline of Annual Research Achievements |
We have developed a high-throughput sleep bioassay system, which is based on the use of electroencephalogram and electromyogram recordings for experimental assessment of sleep and intraperitoneal thermal sensors for the simultaneous measurement of body temperature. In addition, we have used an innovative genetically engineered system to induce hypothermia by activating GABAergic neurons in the median preoptic area (MnPO) of the hypothalamus. Excitatory “designer receptors exclusively activated by designer drugs” (DREADD) involve mutant human muscarinic Gq-protein-coupled receptors (hM3Dq) that are responsive to the inert biologic compound clozapine N-oxide. We stereotaxically microinjected adeno-associated virus coding Cre-dependent hM3Dq DREADD-mCherry into the MnPO of transgenic mice expressing Cre-recombinase under the glutamate decarboxylase 2 (GAD2) promoter (GAD2-Cre mice) to specifically express hM3Dq in GABAergic neurons.
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| Current Status of Research Progress |
Current Status of Research Progress
2: Research has progressed on the whole more than it was originally planned.
Reason
We succeeded in FY2016 in developing a method to induce hypothermia in mice which is the most challenging aspect of the proposed research project. As planned, we will proceed in FY2017 to elucidate effects on memory in our newly developed mouse model of induced hypothermia.
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| Strategy for Future Research Activity |
We will investigate the effects of chemogenetically induced hypothermia on learning and memory in a paradigm based on fear conditioning. Mice are trained to associate a foot shock with the context in which it occurs. Characteristic “freezing” behavior, which entails complete immobility except for breathing, is used as a measure of fear memory. One day after training, freezing is evaluated in two contexts: Context A, which is the context in which the foot shock was delivered, and Context B, which is a novel context used to evaluate memory specificity. In case it does not show any phenotype, another hippocampus dependent memory paradigm, social interaction memory, is utilized.
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