General anesthetics (GA) has been discovered for centuries and was often used in surgeries. However, many patients are dying from the usage of GA for different reasons. Although scientists are working on to solve the problems, the mechanism of GA is still a mystery. Recently, scientists from Duke University found neurons that are active during sleep can be activated in anesthesia. These neurons are called Anesthetic Activated Neurons ( AANs ). This is a massive step for us to break the mystery. In this paper, we designed an experiment that aims to reveal one mechanism of GA: the relationship between sleep-related neurons and sensation of pain under the use of GA. The designed experiment involves several control groups that consist of mice with different treatments on their genes and different GA.
Robinson, D. and Toledo, A. (2012) Historical Development of Modern Anesthesia. Journal of Investigative Surgery, 25, 141-149. https://doi.org/10.3109/08941939.2012.690328
Mayo Clinic (2019) General Anesthesia. http://www.mayoclinic.org/tests-procedures/anesthesia/about/pac-203845683
Alkire, M., Hudetz, A. and Tononi, G. (2008) Consciousness and Anesthesia. Science, 322, 876-880. https://doi.org/10.1126/science.1149213
Lydic, R. and Biebuyck, J. (1994) EDITORIAL II Sleep Neurobiology: Relevance for Mechanistic Studies of Anaesthesia. British Journal of Anaesthesia, 72, 506-508. https://doi.org/10.1093/bja/72.5.506
Nelson, L., Guo, T., Lu, J., Saper, C., Franks, N. and Maze, M. (2002) The Sedative Component of Anesthesia Is Mediated by GABAA Receptors in an Endogenous Sleep Pathway. Nature Neuroscience, 5, 979-984. https://doi.org/10.1038/nn913
Franks, N. (2008) General Anaesthesia: From Molecular Targets to Neuronal Pathways of Sleep and Arousal. Nature Reviews Neuroscience, 9, 370-386. https://doi.org/10.1038/nrn2372
Rudolph, U. and Antkowiak, B. (2004) Molecular and Neuronal Substrates for General Anaesthetics. Nature Reviews Neuroscience, 5, 709-720. https://doi.org/10.1038/nrn1496
Jiang-Xie, L., Yin, L., Zhao, S., Prevosto, V., Han, B., Dzirasa, K. and Wang, F. (2019) A Common Neuroendocrine Substrate for Diverse General Anesthetics and Sleep. Neuron, 102, 1053-1065.E4. https://doi.org/10.1016/j.neuron.2019.03.033
Wigren, H. and Porkka-Heiskanen, T. (2018) Novel Concepts in Sleep Regulation. Acta Physiologica, 222, e13017. https://doi.org/10.1111/apha.13017
Physiology Plus (2019) Pain Pathway Physiology. http://physiologyplus.com/pain-pathway-physiology/
Bercier, V., Rosello, M., Del Bene, F. and Revenu, C. (2019) Zebrafish as a Model for the Study of Live in Vivo Processive Transport in Neurons. Frontiers in Cell and Developmental Biology, 7, 17. https://doi.org/10.3389/fcell.2019.00017
Liu, A., Lai, H., Chang, R. and Gentleman, S. (2017) Free of Acrylamide Sodium Dodecyl Sulphate (SDS)-Based Tissue Clearing (FASTClear): A Novel Protocol of Tissue Clearing for Three-Dimensional Visualization of Human Brain Tissues. Neuropathology and Applied Neurobiology, 43, 346-351. https://doi.org/10.1111/nan.12361
Sakurai, K., Zhao, S., Takatoh, J., Rodriguez, E., Lu, J., Leavitt, A., et al. (2016) Capturing and Manipulating Activated Neuronal Ensembles with CANE Delineates a Hypothalamic Social-Fear Circuit. Neuron, 92, 739-753. https://doi.org/10.1016/j.neuron.2016.10.015
Sherin, J., Elmquist, J., Torrealba, F. and Saper, C. (1998) Innervation of Histaminergic Tuberomammillary Neurons by GABAergic and Galaninergic Neurons in the Ventrolateral Preoptic Nucleus of the Rat. The Journal of Neuroscience, 18, 4705-4721. https://doi.org/10.1523/JNEUROSCI.18-12-04705.1998
Li, X., Zhao, X., Fang, Y., Jiang, X., Duong, T., Fan, C., et al. (1998) Generation of Destabilized Green Fluorescent Protein as a Transcription Reporter. Journal of Biological Chemistry, 273, 34970-34975. https://doi.org/10.1074/jbc.273.52.34970
Kroeger, D., Absi, G., Gagliardi, C., Bandaru, S., Madara, J., Ferrari, L., et al. (2018) Galanin Neurons in the Ventrolateral Preoptic Area Promote Sleep and Heat Loss in Mice. Nature Communications, 9, Article No. 4129. https://doi.org/10.1038/s41467-018-06590-7
Gaus, S., Strecker, R., Tate, B., Parker, R. and Saper, C. (2002) Ventrolateral Preoptic Nucleus Contains Sleep-Active, Galaninergic Neurons in Multiple Mammalian Species. Neuroscience, 115, 285-294. https://doi.org/10.1016/S0306-4522(02)00308-1
Menétrey, D., Gannon, A., Levine, J. and Basbaum, A. (1989) Expression of c-fos Protein in Interneurons and Projection Neurons of the Rat Spinal Cord in Response to Noxious Somatic, Articular, and Visceral Stimulation. Journal of Comparative Neurology, 285, 177-195. https://doi.org/10.1002/cne.902850203
Abbadie, C., Taylor, B., Peterson, A. and Basbaum, A. (1997) Differential Contribution of the Two Phases of the Formalin Test to the Pattern of c-fos Expression in the Rat Spinal Cord: Studies with Remifentanil and Lidocaine. Pain, 69, 101-110. https://doi.org/10.1016/S0304-3959(96)03285-X
Neumann, S., Braz, J., Skinner, K., Llewellyn-Smith, I. and Basbaum, A. (2008) Innocuous, Not Noxious, Input Activates PKC Interneurons of the Spinal Dorsal Horn via Myelinated Afferent Fibers. Journal of Neuroscience, 28, 7936-7944. https://doi.org/10.1523/JNEUROSCI.1259-08.2008
Johnson, Z., Revis, A., Burdick, M. and Rhodes, J. (2010) A Similar Pattern of Neuronal Fos Activation in 10 Brain Regions Following Exposure to Reward- or Aversion-Associated Contextual Cues in Mice. Physiology & Behavior, 99, 412-418. https://doi.org/10.1016/j.physbeh.2009.12.013
Nakai, J., Ohkura, M. and Imoto, K. (2001) A High Signal-to-Noise Ca2+ Probe Composed of a Single Green Fluorescent Protein. Nature Biotechnology, 19, 137-141. https://doi.org/10.1038/84397
Feng, G., Lu, J. and Gross, J. (2004) Generation of Transgenic Mice. In: Luo, Z.D., Ed., Pain Research. Methods in Molecular Medicine, Humana Press, New York, 255-267. https://doi.org/10.1385/1-59259-770-X:155
Chen, Q., Cichon, J., Wang, W., Qiu, L., Lee, S., Campbell, N., et al. (2012) Imaging Neural Activity Using Thy1-GCaMP Transgenic Mice. Neuron, 76, 297-308. https://doi.org/10.1016/j.neuron.2012.07.011