| 研究実績の概要 |
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.
|
| 今後の研究の推進方策 |
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.
|
