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

Hendricks, Michael; Ha, Heonick; Maffey, Nicolas; Zhang, Yun

doi:10.1038/nature11081

Cited by 166 publications

(253 citation statements)

References 29 publications

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“…Recently, several reports have described the important roles for GAR‐3 in neurons, mediating multiple roles in acetylcholine signaling, including acting as an extrasynaptic acetylcholine detector in ventral motor neurons (Hendricks et al ., 2012; Chan et al ., 2013). GAR‐3 is expressed in neurons and the pharyngeal muscle, with particularly high expression in the terminal bulb of the pharynx.…”

Section: Resultsmentioning

confidence: 99%

Chemical activation of a food deprivation signal extends lifespan

Lucanic

Garrett

et al. 2016

Aging Cell

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SummaryModel organisms subject to dietary restriction (DR) generally live longer. Accompanying this lifespan extension are improvements in overall health, based on multiple metrics. This indicates that pharmacological treatments that mimic the effects of DR could improve health in humans. To find new chemical structures that extend lifespan, we screened 30 000 synthetic, diverse drug‐like chemicals in Caenorhabditis elegans and identified several structurally related compounds that acted through DR mechanisms. The most potent of these NP1 impinges upon a food perception pathway by promoting glutamate signaling in the pharynx. This results in the overriding of a GPCR pathway involved in the perception of food and which normally acts to decrease glutamate signals. Our results describe the activation of a dietary restriction response through the pharmacological masking of a novel sensory pathway that signals the presence of food. This suggests that primary sensory pathways may represent novel targets for human pharmacology.

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Section: Resultsmentioning

confidence: 99%

Chemical activation of a food deprivation signal extends lifespan

Lucanic

Garrett

et al. 2016

Aging Cell

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“…Because C. elegans nuclei are thought to be porous to calcium and because the nuclei take up a large portion of the cell body, nuclear recordings used here likely capture calcium transients observed in the cell body. There are, however, known neurons where calcium signals in the processes are different from those in the cell body and, by extension, the nuclei (24,(35)(36)(37). It remains to be seen whether independent calcium dynamics in the processes are unique to these few specific neurons or are a more general phenomenon.…”

Section: Discussionmentioning

confidence: 98%

Whole-brain calcium imaging with cellular resolution in freely behaving Caenorhabditis elegans

Nguyen

Shipley

Linder

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

360

355

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The ability to acquire large-scale recordings of neuronal activity in awake and unrestrained animals is needed to provide new insights into how populations of neurons generate animal behavior. We present an instrument capable of recording intracellular calcium transients from the majority of neurons in the head of a freely behaving Caenorhabditis elegans with cellular resolution while simultaneously recording the animal's position, posture, and locomotion. This instrument provides whole-brain imaging with cellular resolution in an unrestrained and behaving animal. We use spinning-disk confocal microscopy to capture 3D volumetric fluorescent images of neurons expressing the calcium indicator GCaMP6s at 6 head-volumes/s. A suite of three cameras monitor neuronal fluorescence and the animal's position and orientation. Custom software tracks the 3D position of the animal's head in real time and two feedback loops adjust a motorized stage and objective to keep the animal's head within the field of view as the animal roams freely. We observe calcium transients from up to 77 neurons for over 4 min and correlate this activity with the animal's behavior. We characterize noise in the system due to animal motion and show that, across worms, multiple neurons show significant correlations with modes of behavior corresponding to forward, backward, and turning locomotion.calcium imaging | large-scale recording | behavior | C. elegans | microscopy H ow do patterns of neural activity generate an animal's behavior? To answer this question, it is important to develop new methods for recording from large populations of neurons in animals as they move and behave freely. The collective activity of many individual neurons appears to be critical for generating behaviors including arm reach in primates (1), song production in zebrafinch (2), the choice between swimming or crawling in leech (3), and decision-making in mice during navigation (4). New methods for recording from larger populations of neurons in unrestrained animals are needed to better understand neural coding of these behaviors and neural control of behavior more generally.Calcium imaging has emerged as a promising technique for recording dynamics from populations of neurons. Calcium-sensitive proteins are used to visualize changes in intracellular calcium levels in neurons in vivo which serve as a proxy for neural activity (5). To resolve the often weak fluorescent signal of an individual neuron in a dense forest of other labeled cells requires a high magnification objective with a large numerical aperture that, consequently, can image only a small field of view. Calcium imaging has traditionally been performed on animals that are stationary from anesthetization or immobilization to avoid imaging artifacts induced by animal motion. As a result, calcium imaging studies have historically focused on small brain regions in immobile animals that exhibit little or no behavior (6).No previous neurophysiological study has attained whole-brain imaging with cellular resolution in a...

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“…Several neurons in C. elegans exhibit less calcium activity in their soma, with higher activity compartmentalized to their processes (5,32,45). Because processes of the head ganglia are tightly bundled fascicles, our current setup does not allow isolation of signals corresponding to individual neuronal processes.…”

Section: Discussionmentioning

confidence: 99%

Pan-neuronal imaging in roaming Caenorhabditis elegans

Venkatachalam

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

216

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We present an imaging system for pan-neuronal recording in crawling Caenorhabditis elegans. A spinning disk confocal microscope, modified for automated tracking of the C. elegans head ganglia, simultaneously records the activity and position of ∼80 neurons that coexpress cytoplasmic calcium indicator GCaMP6s and nuclear localized red fluorescent protein at 10 volumes per second. We developed a behavioral analysis algorithm that maps the movements of the head ganglia to the animal's posture and locomotion. Image registration and analysis software automatically assigns an index to each nucleus and calculates the corresponding calcium signal. Neurons with highly stereotyped positions can be associated with unique indexes and subsequently identified using an atlas of the worm nervous system. To test our system, we analyzed the brainwide activity patterns of moving worms subjected to thermosensory inputs. We demonstrate that our setup is able to uncover representations of sensory input and motor output of individual neurons from brainwide dynamics. Our imaging setup and analysis pipeline should facilitate mapping circuits for sensory to motor transformation in transparent behaving animals such as C. elegans and Drosophila larva.C. elegans | Drosophila | calcium imaging | thermotaxis U nderstanding how brain dynamics creates behaviors requires quantifying the flow and transformation of sensory information to motor output in behaving animals. Optical imaging using genetically encoded calcium or voltage fluorescent probes offers a minimally invasive method to record neural activity in intact animals. The nematode Caenorhabditis elegans is particularly ideal for optical neurophysiology owing to its small size, optical transparency, compact nervous system, and ease of genetic manipulation. Imaging systems for tracking the activity of small numbers of neurons have been effective in determining their role during nematode locomotion and navigational behaviors like chemotaxis, thermotaxis, and the escape response (1-6).Recordings from large numbers of interconnected neurons are required to understand how neuronal ensembles carry out the systematic transformations of sensory input into motor patterns that build behavioral decisions.Several methods for fast 3D imaging of neural activity in a fixed imaging volume have been developed for different model organisms (7)(8)(9)(10)(11)(12)(13)(14). High-speed light sheet microscopy, light field microscopy, multifocus microscopy, and two-photon structured illumination microscopy have proved effective for rapidly recording large numbers of neurons in immobilized, intact, transparent animals like larval zebrafish and nematodes (15)(16)(17)(18)(19). However, these methods are problematic when attempting to track many neurons within the bending and moving body of a behaving animal. Panneuronal recording in moving animals poses higher demands on spatial and temporal resolution. Furthermore, extracting neuronal signals from recordings in a behaving animal requires an effective analysis pipel...

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

Cited by 166 publications

References 29 publications

Chemical activation of a food deprivation signal extends lifespan

Chemical activation of a food deprivation signal extends lifespan

Whole-brain calcium imaging with cellular resolution in freely behaving Caenorhabditis elegans

Pan-neuronal imaging in roaming Caenorhabditis elegans

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