2. Introduction
3. Materials and Methods
4. Results
5. Discussion
6. Conclusion
5 年以内に雑誌等で刊行予定のため非公開
7. Acknowledgement
My deepest gratitude goes to Dr. Hirofumi Kunitomo and Dr. Yuichi Iino for letting me have
great experiences of PhD course in this laboratory. I thank to Dr. Kunitomo for suggesting the
topic of this study and his kind supervision. Dr. Iino has provided me with unstinting
encouragement, creative and comprehensive advice. This study could not have been possible
without generous helps from Dr. Kunitomo and Dr. Iino.
I would like to express my appreciation to Dr. Masahiro Tomioka, Dr. Yu Toyoshima,
Dr. Moonsun Jang and Dr. Hirofumi Sato for their experimental advice and helps. I am grateful
to Mabardi Llian for proofreading, and Manami Kanamori for experimental assistance. I also
thank to other members of the Y. I. laboratory members for helpful comments and discussion. I
thank to Dr. Yoshitaka Oka and Dr. Shinji Kanda for providing electrophysiology setup and
experimental instruction.
I thank to the Caenorhabditis Genetics Center (CGC) and the National Bioresource
Project (NBRP) for C. elegans strains; Dr. Takeshi Ishihara for pDEST-nls-YC2.60; Dr. Chronis
N., Dr. Albrecht D. and Dr. Bargmann C. for design of microfluidics chips.
8. Reference
Accardi, A. (2015) ‘Structure and gating of CLC channels and exchangers.’, The Journal of
physiology, 593(18), pp. 4129–4138. doi: 10.1113/JP270575.
Adachi, T. et al. (2010) ‘Reversal of salt preference is directed by the insulin/PI3K and G q/PKC
signaling in Caenorhabditis elegans’, Genetics. doi: 10.1534/genetics.110.119768.
Adrian, R. H. and Bryant, S. H. (1974) ‘On the repetitive discharge in myotonic muscle fibres’,
The Journal of Physiology. doi: 10.1113/jphysiol.1974.sp010620.
Ahnert-Hilger, G. and Jahn, R. (2011) ‘CLC-3 spices up GABAergic synaptic vesicles’, Nature
Neuroscience. doi: 10.1038/nn.2786.
Albrecht, D. R. and Bargmann, C. I. (2011) ‘High-content behavioral analysis of Caenorhabditis
elegans in precise spatiotemporal chemical environments’, Nature Methods. doi:
10.1038/nmeth.1630.
Bacaj, T. et al. (2008) ‘Glia are essential for sensory organ function in C. elegans.’, Science
(New York, N.Y.), 322(5902), pp. 744–7. doi: 10.1126/science.1163074.
Bargmann, C. I., Hartwieg, E. and Horvitz, H. R. (1993) ‘Odorant-selective genes and neurons
mediate olfaction in C. elegans’, Cell, 74(3), pp. 515–527. doi: 10.1016/0092-8674(93)80053-H.
Bargmann, C. I. and Horvitz, H. R. (1991) ‘Chemosensory neurons with overlapping functions
direct chemotaxis to multiple chemicals in C. elegans’, Neuron, 7(5), pp. 729–742. doi:
10.1016/0896-6273(91)90276-6.
Blanz, J. et al. (2007) ‘Leukoencephalopathy upon disruption of the chloride channel ClC-2’,
Journal of Neuroscience. doi: 10.1523/JNEUROSCI.0338-07.2007.
Blaxter, M. and Denver, D. R. (2012) ‘The worm in the world and the world in the worm’, BMC
Biology. doi: 10.1186/1741-7007-10-57.
Bösl, M. R. et al. (2001) ‘Male germ cells and photoreceptors, both dependent on close cell-cell
interactions, degenerate upon ClC-2 Cl- channel disruption’, EMBO Journal. doi:
10.1093/emboj/20.6.1289.
Branicky, R. et al. (2014) ‘The voltage-gated anion channels encoded by clh-3 regulate egg
laying in C. elegans by modulating motor neuron excitability’, Journal of Neuroscience. doi:
10.1523/JNEUROSCI.3112-13.2014.
Braubach, O. R. et al. (2009) ‘Olfactory conditioning in the zebrafish (Danio rerio)’,
Behavioural Brain Research. doi: 10.1016/j.bbr.2008.10.044.
Brenner, S. (1974) ‘The genetics of Caenorhabditis elegans.’, Genetics, 77(1), pp. 71–94. doi:
10.1002/cbic.200300625.
Chalasani, S. H. et al. (2007) ‘Dissecting a circuit for olfactory behaviour in Caenorhabditis
elegans’, Nature. doi: 10.1038/nature06292.
Charlet-B., N. et al. (2002) ‘Loss of the muscle-specific chloride channel in type 1 myotonic
dystrophy due to misregulated alternative splicing’, Molecular Cell. doi: 10.1016/S10972765(02)00572-5.
Chen, D. Y. et al. (2011) ‘A critical role for IGF-II in memory consolidation and enhancement’,
Nature. doi: 10.1038/nature09667.
Chen, Y. F. et al. (2019) ‘Knockdown of CLC-3 in the hippocampal CA1 impairs contextual fear
memory’, Progress in Neuro-Psychopharmacology and Biological Psychiatry. doi:
10.1016/j.pnpbp.2018.07.004.
Cho, C. E. et al. (2016) ‘Parallel encoding of sensory history and behavioral preference during
Caenorhabditis elegans olfactory learning’, eLife. doi: 10.7554/eLife.14000.
Chronis, N., Zimmer, M. and Bargmann, C. I. (2007) ‘Microfluidics for in vivo imaging of
neuronal and behavioral activity in Caenorhabditis elegans’, Nature Methods. doi:
10.1038/nmeth1075.
Colbert, H. A. and Bargmann, C. I. (1995) ‘Odorant-specific adaptation pathways generate
olfactory plasticity in C. elegans’, Neuron. doi: 10.1016/0896-6273(95)90224-4.
Deidda, G. et al. (2015) ‘Reversing excitatory GABA A R signaling restores synaptic plasticity
and memory in a mouse model of Down syndrome’, Nature Medicine. doi: 10.1038/nm.3827.
Dutzler, R. et al. (2002) ‘X-ray structure of a CIC chloride channel at 3.0 Å reveals the
molecular basis of anion selectivity’, Nature. doi: 10.1038/415287a.
Fahlke, C. et al. (1995) ‘An aspartic acid residue important for voltage-dependent gating of
human muscle chloride channels’, Neuron. doi: 10.1016/0896-6273(95)90050-0.
Félix, M. A. and Duveau, F. (2012) ‘Population dynamics and habitat sharing of natural
populations of Caenorhabditis elegans and C. briggsae’, BMC Biology. doi: 10.1186/1741-700710-59.
Fernandes-Rosa, F. L. et al. (2018) ‘A gain-of-function mutation in the CLCN2 chloride channel
gene causes primary aldosteronism’, Nature Genetics. Springer US, 50(March), pp. 1–7. doi:
10.1038/s41588-018-0053-8.
Gong, J. et al. (2019) ‘A Cold-Sensing Receptor Encoded by a Glutamate Receptor Gene’, Cell.
doi: 10.1016/j.cell.2019.07.034.
Gordus, A. et al. (2015) ‘Feedback from network states generates variability in a probabilistic
olfactory circuit’, Cell. doi: 10.1016/j.cell.2015.02.018.
Gottfried, J. A., O’Doherty, J. and Dolan, R. J. (2003) ‘Encoding predictive reward value in
human amygdala and orbitofrontal cortex’, Science. doi: 10.1126/science.1087919.
Gottschalk, A. et al. (2005) ‘Identification and characterization of novel nicotinic receptorassociated proteins in Caenorhabditis elegans’, EMBO Journal. doi: 10.1038/sj.emboj.7600741.
Govorunova, E. G. et al. (2015) ‘Natural light-gated anion channels: A family of microbial
rhodopsins for advanced optogenetics’, Science. doi: 10.1126/science.aaa7484.
Grant, J., Matthewman, C. and Bianchi, L. (2015) ‘A Novel Mechanism of pH Buffering in C.
elegans Glia: Bicarbonate Transport via the Voltage-Gated ClC Cl- Channel CLH-1’, Journal of
Neuroscience, 35(50), pp. 16377–16397. doi: 10.1523/JNEUROSCI.3237-15.2015.
Gray, J. M., Hill, J. J. and Bargmann, C. I. (2005) ‘A circuit for navigation in Caenorhabditis
elegans’, Proceedings of the National Academy of Sciences of the United States of America. doi:
10.1073/pnas.0409009101.
10
Grimley, J. S. et al. (2013) ‘Visualization of synaptic inhibition with an optogenetic sensor
developed by cell-free protein engineering automation’, Journal of Neuroscience. doi:
10.1523/JNEUROSCI.4616-11.2013.
Hata, Y., Slaughter, C. A. and Südhof, T. C. (1993) ‘Synaptic vesicle fusion complex contains
unc-18 homologue bound to syntaxin’, Nature. doi: 10.1038/366347a0.
Hedgecock, E. M. and Russell, R. L. (1975) ‘Normal and mutant thermotaxis in the nematode
Caenorhabditis elegans’, Proceedings of the National Academy of Sciences of the United States
of America. doi: 10.1073/pnas.72.10.4061.
Hirano, Y. et al. (2013) ‘Fasting launches CRTC to facilitate long-term memory formation in
Drosophila’, Science. doi: 10.1126/science.1227170.
Horikawa, K. et al. (2010) ‘Spontaneous network activity visualized by ultrasensitive Ca 2+
indicators, yellow Cameleon-Nano’, Nature Methods. doi: 10.1038/nmeth.1488.
Iino, Y. and Yoshida, K. (2009) ‘Parallel use of two behavioral mechanisms for chemotaxis in
Caenorhabditis elegans.’, The Journal of neuroscience : the official journal of the Society for
Neuroscience, 29(17), pp. 5370–5380. doi: 10.1523/JNEUROSCI.3633-08.2009.
Iwata, R. et al. (2011) ‘Roles for class IIA phosphatidylinositol transfer protein in
neurotransmission and behavioral plasticity at the sensory neuron synapses of Caenorhabditis
elegans’, Proceedings of the National Academy of Sciences of the United States of America. doi:
10.1073/pnas.1016232108.
Jang, M. S. et al. (2019) ‘Multiple sensory neurons mediate starvation-dependent aversive
navigation in Caenorhabditis elegans’, Proceedings of the National Academy of Sciences of the
United States of America. doi: 10.1073/pnas.1821716116.
Jentsch, T. J. (2007) ‘Chloride and the endosomal-lysosomal pathway: Emerging roles of CLC
chloride transporters’, Journal of Physiology. doi: 10.1113/jphysiol.2006.124719.
Jentsch, T. J. (2008) CLC Chloride Channels and Transporters: From Genes to Protein
Structure, Pathology and Physiology, Critical Reviews in Biochemistry and Molecular Biology.
doi: 10.1080/10409230701829110.
11
Jeworutzki, E. et al. (2014) ‘GlialCAM, a CLC-2 Cl- channel subunit, activates the slow gate of
CLC chloride channels’, Biophysical Journal. doi: 10.1016/j.bpj.2014.07.040.
Kindt, K. S. et al. (2007) ‘Dopamine Mediates Context-Dependent Modulation of Sensory
Plasticity in C. elegans’, Neuron. doi: 10.1016/j.neuron.2007.07.023.
Kunitomo, H. et al. (2013) ‘Concentration memory-dependent synaptic plasticity of a taste
circuit regulates salt concentration chemotaxis in Caenorhabditis elegans.’, Nature
communications. Nature Publishing Group, 4(May), p. 2210. doi: 10.1038/ncomms3210.
Kuramochi, M. and Doi, M. (2019) ‘An excitatory/inhibitory switch from asymmetric sensory
neurons defines postsynaptic tuning for a rapid response to NaCl in Caenorhabditis elegans’,
Frontiers in Molecular Neuroscience. doi: 10.3389/fnmol.2018.00484.
Lewis, J. A. et al. (1980) ‘The genetics of levamisole resistance in the nematode Caenorhabditis
elegans’, Genetics.
Li, Z. et al. (2014) ‘Encoding of both analog- and digital-like behavioral outputs by one C.
Elegans interneuron’, Cell. doi: 10.1016/j.cell.2014.09.056.
Liu, J. et al. (2010) ‘C. elegans phototransduction requires a G protein-dependent cGMP
pathway and a taste receptor homolog’, Nature Neuroscience. doi: 10.1038/nn.2540.
López-Cruz, A. et al. (2019) ‘Parallel Multimodal Circuits Control an Innate Foraging
Behavior’, Neuron. doi: 10.1016/j.neuron.2019.01.053.
Luo, L. et al. (2014) ‘Dynamic encoding of perception, memory, and movement in a C. elegans
chemotaxis circuit’, Neuron. doi: 10.1016/j.neuron.2014.05.010.
Nagashima, T., Iino, Y. and Tomioka, M. (2019) ‘DAF-16/FOXO promotes taste avoidance
learning independently of axonal insulin-like signaling’, PLoS Genetics. doi:
10.1371/journal.pgen.1008297.
Nehrke, K. et al. (2000) ‘Into ion channel and transporter function. Caenorhabditis elegans ClCtype chloride channels: novel variants and functional expression.’, American journal of
physiology. Cell physiology, 279(6), pp. C2052-66. Available at:
http://www.ncbi.nlm.nih.gov/pubmed/11078724.
12
O’Doherty, J. P. et al. (2003) ‘Temporal difference models and reward-related learning in the
human brain’, Neuron. doi: 10.1016/S0896-6273(03)00169-7.
Oda, S., Tomioka, M. and Iino, Y. (2011) ‘Neuronal plasticity regulated by the insulin-like
signaling pathway underlies salt chemotaxis learning in Caenorhabditis elegans’, Journal of
Neurophysiology. doi: 10.1152/jn.01029.2010.
Ohno, H. et al. (2014) ‘Role of synaptic phosphatidylinositol 3-kinase in a behavioral learning
response in C. elegans.’, Science, 345(6194), pp. 313–317. doi: 10.1126/science.1250709.
Ohno, H. et al. (2017) ‘Dynamics of Presynaptic Diacylglycerol in a Sensory Neuron Encode
Differences between Past and Current Stimulus Intensity’, Cell Reports. doi:
10.1016/j.celrep.2017.08.038.
Ortiz, C. O. et al. (2009) ‘Lateralized Gustatory Behavior of C. elegans Is Controlled by Specific
Receptor-Type Guanylyl Cyclases’, Current Biology, 19(12), pp. 996–1004. doi:
10.1016/j.cub.2009.05.043.
Otis, J. M. et al. (2017) ‘Prefrontal cortex output circuits guide reward seeking through divergent
cue encoding’, Nature. doi: 10.1038/nature21376.
Pavlov, I. P. (1927) Classics in the History of Psychology -- Pavlov (1927) Lecture 2,
CONDITIONED REFLEXES: AN INVESTIGATION OF THE PHYSIOLOGICAL ACTIVITY OF
THE CEREBRAL CORTEX.
Perkins, L. A. et al. (1986) ‘Mutant sensory cilia in the nematode Caenorhabditis elegans’,
Developmental Biology. doi: 10.1016/0012-1606(86)90314-3.
Petalcorin, M. I. R. et al. (1999) ‘Disruption of clh-1, a chloride channel gene, results in a wider
body of Caenorhabditis elegans’, Journal of Molecular Biology. doi: 10.1006/jmbi.1999.3241.
Pfeffer, C. K. et al. (2009) ‘NKCC1-dependent GABAergic excitation drives synaptic network
maturation during early hippocampal development’, Journal of Neuroscience. doi:
10.1523/JNEUROSCI.1377-08.2009.
13
Pierce-Shimomura, J. T., Morse, T. M. and Lockery, S. R. (1999) ‘The fundamental role of
pirouettes in Caenorhabditis elegans chemotaxis’, Journal of Neuroscience. doi:
10.1523/jneurosci.19-21-09557.1999.
Piggott, B. J. et al. (2011) ‘The neural circuits and synaptic mechanisms underlying motor
initiation in C. elegans’, Cell. doi: 10.1016/j.cell.2011.08.053.
Pristerà, A. et al. (2019) ‘Dopamine neuron-derived IGF-1 controls dopamine neuron firing, skill
learning, and exploration’, Proceedings of the National Academy of Sciences of the United States
of America. doi: 10.1073/pnas.1806820116.
Pusch, M. et al. (1995) ‘Mutations in dominant human myotonia congenita drastically alter the
voltage dependence of the CIC-1 chloride channel’, Neuron. doi: 10.1016/0896-6273(95)900233.
Ratté, S. and Prescott, S. A. (2011) ‘CLC-2 channels regulate neuronal excitability, not
intracellular chloride levels’, Journal of Neuroscience. doi: 10.1523/JNEUROSCI.2748-11.2011.
Rea, S. L. et al. (2005) ‘A stress-sensitive reporter predicts longevity in isogenic populations of
Caenorhabditis elegans’, Nature Genetics. doi: 10.1038/ng1608.
Redemann, S. et al. (2011) ‘Codon adaptation-based control of protein expression in C. elegans’,
Nature Methods. doi: 10.1038/nmeth.1565.
Rhodes, T. H. et al. (1999) ‘A missense mutation in canine ClC-1 causes recessive myotonia
congenita in the dog’, FEBS Letters. doi: 10.1016/S0014-5793(99)00926-6.
Rinke, I., Artmann, J. and Stein, V. (2010) ‘ClC-2 voltage-gated channels constitute part of the
background conductance and assist chloride extrusion’, Journal of Neuroscience. doi:
10.1523/JNEUROSCI.6299-09.2010.
Saeki, S., Yamamoto, M. and Iino, Y. (2001) ‘Plasticity of chemotaxis revealed by paired
presentation of a chemoattractant and starvation in the nematode Caenorhabditis elegans’,
Journal of Experimental Biology.
14
Sakurai, Y. (2010) ‘線虫 C. elegans の餌と連合した塩濃度学習の遺伝学的解析 (Genetic
analyses for characterization of the food-associated salt chemotaxis learning mechanism in C.
elegans)’, Master’s thesis, Dept. of Biol. Sci., The Univ. of Tokyo.
Sasakura, H. and Mori, I. (2013) ‘Behavioral plasticity, learning, and memory in C. elegans’,
Current Opinion in Neurobiology. doi: 10.1016/j.conb.2012.09.005.
Satoh, Y. et al. (2014) ‘Regulation of experience-dependent bidirectional chemotaxis by a neural
circuit switch in Caenorhabditis elegans’, Journal of Neuroscience. doi:
10.1523/JNEUROSCI.1757-14.2014.
Schafer, W. R. and Kenyon, C. J. (1995) ‘A calcium-channel homologue required for adaptation
to dopamine and serotonin in Caenorhabditis elegans’, Nature. doi: 10.1038/375073a0.
Schriever, AM. et al. (1999) ‘CLC chloride channels in Caenorhabditis elegans.’, Journal of
Biological Chemistry.
Serrano-Saiz, E. et al. (2013) ‘XModular control of glutamatergic neuronal identity in C. elegans
by distinct homeodomain proteins’, Cell. doi: 10.1016/j.cell.2013.09.052.
Shindou, T. et al. (2019) ‘Active propagation of dendritic electrical signals in C. elegans’,
Scientific Reports. doi: 10.1038/s41598-019-40158-9.
Sieburth, D., Madison, J. M. and Kaplan, J. M. (2007) ‘PKC-1 regulates secretion of
neuropeptides’, Nature Neuroscience. doi: 10.1038/nn1810.
Singhvi, A. et al. (2016) ‘A Glial K/Cl Transporter Controls Neuronal Receptive Ending Shape
by Chloride Inhibition of an rGC’, Cell. Elsevier Inc., 165(4), pp. 936–948. doi:
10.1016/j.cell.2016.03.026.
Smith, H. K. et al. (2013) ‘Defining specificity determinants of cGMP mediated gustatory
sensory transduction in Caenorhabditis elegans’, Genetics. doi: 10.1534/genetics.113.152660.
Staley, K. et al. (1996) ‘Alteration of GABA(A) receptor function following gene transfer of the
CLC-2 chloride channel’, Neuron. doi: 10.1016/S0896-6273(00)80186-5.
15
Staley, K. J., Soldo, B. L. and Proctor, W. R. (1995) ‘Ionic mechanisms of neuronal excitation by
inhibitory GABAA receptors’, Science. doi: 10.1126/science.7638623.
Stauber, T., Weinert, T. and Jentsch, T. J. (2012) ‘Cell biology and physiology of CLC chloride
channels and transporters’, Comprehensive Physiology. doi: 10.1002/cphy.c110038.
Stölting, G., Fischer, M. and Fahlke, C. (2014a) ‘ClC-1 and ClC-2 form hetero-dimeric channels
with novel protopore functions’, Pflugers Archiv European Journal of Physiology. doi:
10.1007/s00424-014-1490-6.
Stölting, G., Fischer, M. and Fahlke, C. (2014b) ‘CLC channel function and dysfunction in
health and disease’, Frontiers in Physiology, 5(OCT), pp. 1–18. doi: 10.3389/fphys.2014.00378.
Summers, P. J. et al. (2015) ‘Multiple sensory inputs are extensively integrated to modulate
nociception in C. elegans’, Journal of Neuroscience. doi: 10.1523/JNEUROSCI.0225-15.2015.
Suzuki, H. et al. (2008) ‘Functional asymmetry in Caenorhabditis elegans taste neurons and its
computational role in chemotaxis.’, Nature, 454(7200), pp. 114–7. doi: 10.1038/nature06927.
Thiemann, A. et al. (1992) ‘A chloride channel widely expressed in epithelial and non-epithelial
cells’, Nature. doi: 10.1038/356057a0.
Tomioka, M. et al. (2006) ‘The Insulin/PI 3-Kinase Pathway Regulates Salt Chemotaxis
Learning in Caenorhabditis elegans’, Neuron, 51(5), pp. 613–625. doi:
10.1016/j.neuron.2006.07.024.
Tsalik, E. L. and Hobert, O. (2003) ‘Functional mapping of neurons that control locomotory
behavior in Caenorhabditis elegans’, Journal of Neurobiology. doi: 10.1002/neu.10245.
Ventimiglia, D. and Bargmann, C. I. (2017) ‘Diverse modes of synaptic signaling, regulation,
and plasticity distinguish two classes of C. elegans glutamatergic neurons’, eLife. doi:
10.7554/eLife.31234.
Wang, L. et al. (2017) ‘A gustatory neural circuit of Caenorhabditis elegans generates memorydependent behaviors in Na+ chemotaxis’, Journal of Neuroscience. doi:
10.1523/JNEUROSCI.1774-16.2017.
16
Ware, R. W. et al. (1975) ‘The nerve ring of the nematode Caenorhabditis elegans: Sensory input
and motor output’, Journal of Comparative Neurology. doi: 10.1002/cne.901620106.
White, J. G. et al. (1986) ‘The structure of the nervous system of the nematode Caenorhabditis
elegans.’, Philosophical Transactions of the Royal Society of London, 314(1165), pp. 1–340. doi:
10.1098/rstb.1986.0056.
Winter, Y. and Stich, K. P. (2005) ‘Foraging in a complex naturalistic environment: Capacity of
spatial working memory in flower bats’, Journal of Experimental Biology. doi:
10.1242/jeb.01416.
Wu, F.-F. (2002) ‘Novel CLCN1 mutations with unique clinical and electrophysiological
consequences’, Brain, 125(11), pp. 2392–2407. doi: 10.1093/brain/awf246.
Yamamoto, T. et al. (2015) ‘Single Nucleotide variations in CLCN6 identified in patients with
benign partial epilepsies in infancy and/or febrile seizures’, PLoS ONE. doi:
10.1371/journal.pone.0118946.
Zou, W. et al. (2018) ‘Decoding the intensity of sensory input by two glutamate receptors in one
C. elegans interneuron’, Nature Communications. doi: 10.1038/s41467-018-06819-5.
Zullo, J. M. et al. (2019) ‘Regulation of lifespan by neural excitation and REST’, Nature. doi:
10.1038/s41586-019-1647-8.
17
...
論文の公開元へ
