The confinement of neuronal activity to specific subcellular regions is a mechanism for expanding the computational properties of neurons. Although the circuit organization underlying compartmentalized activity has been studied in several systems1,2,3,4, its cellular basis is still unknown. Here we characterize compartmentalized activity in Caenorhabditis elegans RIA interneurons, which have multiple reciprocal connections to head motor neurons and receive input from sensory pathways. We show that RIA spatially encodes head movement on a subcellular scale through axonal compartmentalization. This subcellular axonal activity is dependent on acetylcholine release from head motor neurons and is simultaneously present and additive with glutamate-dependent globally synchronized activity evoked by sensory inputs. Postsynaptically, the muscarinic acetylcholine receptor GAR-3 acts in RIA to compartmentalize axonal activity through the mobilization of intracellular calcium stores. The compartmentalized activity functions independently of the synchronized activity to modulate locomotory behaviour.
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Euler, T., Detwiler, P. B. & Denk, W. Directionally selective calcium signals in dendrites of starburst amacrine cells. Nature 418, 845–852 (2002)
Borst, A. & Euler, T. Seeing things in motion: models, circuits, and mechanisms. Neuron 71, 974–994 (2011)
Rall, W., Shepherd, G. M., Reese, T. S. & Brightman, M. W. Dendrodendritic synaptic pathway for inhibition in the olfactory bulb. Exp. Neurol. 14, 44–56 (1966)
Zhu, J. & Heggelund, P. Muscarinic regulation of dendritic and axonal outputs of rat thalamic interneurons: a new cellular mechanism for uncoupling distal dendrites. J. Neurosci. 21, 1148–1159 (2001)
White, J. G., Southgate, E., Thomson, J. N. & Brenner, S. The structure of the nervous system of the nematode Caenorhabditis elegans . Phil. Trans. R. Soc. Lond. B 314, 1–340 (1986)
Varshney, L. R., Chen, B. L., Paniagua, E., Hall, D. H. & Chklovskii, D. B. Structural properties of the Caenorhabditis elegans neuronal network. PLOS Comput. Biol. 7, e1001066 (2011)
Ha, H.-I. et al. Functional organization of a neural network for aversive olfactory learning in Caenorhabditis elegans . Neuron 68, 1173–1186 (2010)
Gray, J. M., Hill, J. J. & Bargmann, C. I. A circuit for navigation in Caenorhabditis elegans . Proc. Natl Acad. Sci. USA 102, 3184–3191 (2005)
Tian, L. et al. Imaging neural activity in worms, flies and mice with improved GCaMP calcium indicators. Nature Methods 6, 875–881 (2009)
Brockie, P. J., Madsen, D. M., Zheng, Y., Mellem, J. & Maricq, A. V. Differential expression of glutamate receptor subunits in the nervous system of Caenorhabditis elegans and their regulation by the homeodomain protein UNC-42. J. Neurosci. 21, 1510–1522 (2001)
Chronis, N., Zimmer, M. & Bargmann, C. I. Microfluidics for in vivo imaging of neuronal and behavioral activity in Caenorhabditis elegans . Nature Methods 4, 727–731 (2007)
Chalasani, S. H. et al. Dissecting a circuit for olfactory behaviour in Caenorhabditis elegans . Nature 450, 63–70 (2007)
Clark, D. A., Biron, D., Sengupta, P. & Samuel, A. D. T. The AFD sensory neurons encode multiple functions underlying thermotactic behavior in Caenorhabditis elegans . J. Neurosci. 26, 7444–7451 (2006)
Hart, A. C., Sims, S. & Kaplan, J. M. Synaptic code for sensory modalities revealed by C. elegans GLR-1 glutamate receptor. Nature 378, 82–85 (1995)
Macosko, E. Z. et al. A hub-and-spoke circuit drives pheromone attraction and social behaviour in C. elegans . Nature 458, 1171–1175 (2009)
Schiavo, G. et al. Tetanus and botulinum-B neurotoxins block neurotransmitter release by proteolytic cleavage of synaptobrevin. Nature 359, 832–835 (1992)
Wang, X. et al. The C. elegans L1CAM homologue LAD-2 functions as a coreceptor in MAB-20/Sema2 mediated axon guidance. J. Cell Biol. 180, 233–246 (2008)
Rand, J. B. & Nonet, M. L. in C. elegans II (eds Riddle, D. L., Blumenthal, T., Meyer, B. J. & Priess, J. R. ) 611–643 (Cold Spring Harbor Laboratory Press, 1997)
Goodman, M. B., Hall, D. H., Avery, L. & Lockery, S. R. Active currents regulate sensitivity and dynamic range in C. elegans neurons. Neuron 20, 763–772 (1998)
Park, Y.-S., Kim, S., Shin, Y., Choi, B. & Cho, N. J. Alternative splicing of the muscarinic acetylcholine receptor GAR-3 in Caenorhabditis elegans . Biochem. Biophys. Res. Commun. 308, 961–965 (2003)
Liu, Y., LeBoeuf, B. & Garcia, L. R. Gαq-coupled muscarinic acetylcholine receptors enhance nicotinic acetylcholine receptor signaling in Caenorhabditis elegans mating behavior. J. Neurosci. 27, 1411–1421 (2007)
Steger, K. A. & Avery, L. The GAR-3 muscarinic receptor cooperates with calcium signals to regulate muscle contraction in the Caenorhabditis elegans pharynx. Genetics 167, 633–643 (2004)
Hulme, E. C., Birdsall, N. J. & Buckley, N. J. Muscarinic receptor subtypes. Annu. Rev. Pharmacol. Toxicol. 30, 633–673 (1990)
Miller, K. G., Emerson, M. D. & Rand, J. B. Goα and diacylglycerol kinase negatively regulate the Gqα pathway in C. elegans . Neuron 24, 323–333 (1999)
Lackner, M. R., Nurrish, S. J. & Kaplan, J. M. Facilitation of synaptic transmission by EGL-30 Gqα and EGL-8 PLCβ: DAG binding to UNC-13 is required to stimulate acetylcholine release. Neuron 24, 335–346 (1999)
Crapse, T. B. & Sommer, M. A. Corollary discharge across the animal kingdom. Nature Rev. Neurosci. 9, 587–600 (2008)
Lockery, S. R. The computational worm: spatial orientation and its neuronal basis in C. elegans . Curr. Opin. Neurobiol. 21, 782–790 (2011)
Joesch, M., Schnell, B., Raghu, S. V., Reiff, D. F. & Borst, A. ON and OFF pathways in Drosophila motion vision. Nature 468, 300–304 (2010)
Brenner, S. The genetics of Caenorhabditis elegans . Genetics 77, 71–94 (1974)
Mello, C. C., Kramer, J. M., Stinchcomb, D. & Ambros, V. Efficient gene transfer in C. elegans: extrachromosomal maintenance and integration of transforming sequences. EMBO J. 10, 3959–3970 (1991)
We thank the Caenorhabditis Genetics Center and C. elegans Gene Knockout Consortium for C. elegans strains; the Wellcome Trust Sanger Institute for cosmid; C. Bargmann for the TeTx cDNA, eat-4 cDNA and Pttx-3::GCaMP strain; Y. Kohara for the gar-3 cDNA; J. Nakai for the GCaMP DNA; N. Bhatla for help with integration; L. Tian and L. Looger for the GCaMP3.3 plasmid; Y. Shen for the lad-2 promoter; and C. Bargmann, K. Blum, F. Engert, C. Fang-Yen, S. Hendricks, S. Jesuthasan, A. Samuel, J. Sanes, E. Soucy and members of the Zhang laboratory for advice and discussion. M.H. thanks S. Moser for personal support. This work was supported by funding from The Esther A. and Joseph Klingenstein Fund, the March of Dimes Foundation, the Alfred P. Sloan Foundation, the John Merck Fund and the National Institutes of Health (DC009852) to Y.Z.
The authors declare no competing financial interests.
This file contains Supplementary Figures 1-5 which show the calcium imaging analysis of C. elegans interneurons RIA and motor neurons SMDs. (PDF 9130 kb)
This file contains Supplementary Movie 1 which shows the compartmentalized calcium signals in RIA axonal domains and the head movement of a transgenic animal that expresses GCaMP3 in RIA interneuron. It demonstrates that calcium signals in the ventral and dorsal RIA axonal compartments in the nerve ring (nrV and nrD) correlate with ventral and dorsal head bending, respectively. Anterior is to the left. Dorsal is up and ventral is down. (MOV 11629 kb)
This file contains Supplementary Movie 2 which shows neuronal calcium signals and head movement of a transgenic animal that expresses GCaMP3 in SMDV, SMDD motor neurons and several other neurons in the head. It shows that the calcium signals in SMDV and SMDD correlate with ventral and dorsal head bending, respectively. Anterior is to the left. Dorsal is up and ventral is down. (MOV 2598 kb)
This file contains Supplementary Movie 3 which shows that the compartmentalized calcium signals in different RIA axonal domains persist in an animal that is paralyzed with the nicotinic acetylcholine receptor agonist levamisole. Anterior is to the left. Dorsal is up and ventral is down. (MOV 2241 kb)
This file contains Supplementary Movie 4 which shows that oscillatory calcium dynamics in SMDV and SMDD motor neurons persist in an animal that is paralyzed with the nicotinic acetylcholine receptor agonist levamisole. Anterior is to the left. Dorsal is up and ventral is down. (MOV 4609 kb)
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Hendricks, M., Ha, H., Maffey, N. et al. Compartmentalized calcium dynamics in a C. elegans interneuron encode head movement. Nature 487, 99–103 (2012). https://doi.org/10.1038/nature11081
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