Compartmentalized calcium dynamics in a C. elegans interneuron encode head movement

Abstract

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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Figure 1: Compartmentalized calcium signals in RIA encode head movement.
Figure 2: RIA compartmentalized activity requires transmission from SMD motor neurons.
Figure 3: A muscarinic acetylcholine pathway establishes motor-correlated RIA dynamics.
Figure 4: Sensory-evoked synchronized RIA activity is dependent on glutamate-dependent transmission and is additive with compartmentalized dynamics.

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Acknowledgements

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.

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M.H. and Y.Z. designed experiments, analysed data, interpreted results and wrote the paper. M.H., H.H. and N.M. performed experiments.

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Correspondence to Yun Zhang.

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The authors declare no competing financial interests.

Supplementary information

Supplementary Information

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)

Supplementary Movie 1

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)

Supplementary Movie 2

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)

Supplementary Movie 3

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)

Supplementary Movie 4

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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