主催: The Japanese Pharmacological Society, The Japanese Society of Clinical Pharmacology
会議名: WCP2018 (18th World Congress of Basic and Clinical Pharmacology)
開催地: Kyoto
開催日: 2018/07/01 - 2018/07/06
Diverse cells underlie basic drives and actions essential for animal survival, including behaviors such as those related to thirst, hunger, and sleep. Cell-type-specific activity signals that underlie these animal behaviors have been elucidated, interestingly, using proteins essential for plant behaviors1. These channelrhodopsin proteins are light-gated ion channels that enable motile algae to seek light conditions suitable for photosynthesis1; we have been able to discover principles of function by solving the key high-resolution channelrhodopsin crystal structures and by structure-guided redesign for altered ion selectivity, kinetics, and spectral properties1,2. These discoveries not only revealed basic principles governing operation of light-gated ion channels for plant survival-drive behavior, but also enabled the creation of new proteins for illuminating (via optogenetics)3 fundamental animal survival-drive behavior via application to circuit function. Here we will present our structures and structure-guided tool redesign outcomes, and our application of these tools to uncover basic hypothalamic mechanisms underlying thirst4,5, feeding6,7, sleep8, and other fundamental drives9, via identification of internal cellular-resolution brain states that dynamically control the elements of drive-motivated behavior. And we will present in detail a new general method for identifying the cellular manifestation of internal states by integrating brain-wide single-cell activity imaging and control with hydrogel-tissue chemistry10 for high-content cellular-resolution molecular phenotyping11. Together, these experiments have established an approach for unbiased discovery of cellular elements underlying behavior, and have revealed an evolutionarily-conserved set of diverse cellular systems that collectively govern survival drive-related internal states.
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2Kato et al. (2012). Crystal structure of the channelrhodopsin light-gated cation channel. Nature 482: 369-74.
3Deisseroth K (2015). Optogenetics: ten years of microbial opsins in neuroscience. Nature Neuroscience 18: 1213-25.
4Allen WE et al. (2017). Thirst-associated preoptic neurons encode an aversive motivational drive. Science 357: 1149-55.
5Augustine et al. (2018). Hierarchical neural architecture underlying thirst regulation. Nature, doi: 10.1038/nature25488.
6Domingos et al. (2011). Leptin regulates the reward value of nutrient. Nature Neuroscience 14: 1562-8.
7Ferenczi et al. (2016). Prefrontal regulation of brainwide circuit dynamics and reward-related behavior. Science 351 (6268): aac9698.
8Adamantidis et al. (2007). Neural substrates of awakening probed with optogenetic control of hypocretin neurons. Nature 450: 420-4.
9Kim et al. (2013). Assembling behavioral states: divergent neural pathways recruit separable anxiety features. Nature 496: 219-23.
10Gradinaru et al. (2018). Hydrogel-tissue chemistry: principles and applications. Annual Review of Biophysics, in press.
11Lovett-Barron et al. (2017). Ancestral circuits for the coordinated modulation of brain state. Cell 171: 1411-23.
