Trends in high‐throughput and functional neuroimaging in Caenorhabditis elegans

Abstract

The nervous system of Caenorhabditis elegans is an important model system for understanding the development and function of larger, more complex nervous systems. It is prized for its ease of handling, rapid life cycle, and stereotyped, well-cataloged development, with the development of all 302 neurons mapped all the way from zygote to adult. The combination of easy genetic manipulation and optical transparency of the worm allows for the direct imaging of its interior with fluorescent microscopy, without physically compromising the normal physiology of the animal itself. By expressing fluorescent markers, biologists study many developmental and cell biology questions in vivo; by expressing genetically encoded fluorescent calcium indicators within neurons, it is also possible to monitor their dynamic activity, answering questions about the structure and function of neural microcircuitry in the worm. However, to successfully image the worm it is necessary to overcome a number of experimental challenges. It is necessary to hold worms within the field of view, collect images efficiently and rapidly, and robustly analyze the data obtained. In recent years, a trend has developed toward imaging a large number of worms or neurons simultaneously, directly exploiting the unique properties of C. elegans to acquire data on a scale, which is not possible in other organisms. Doing this has required the development of new experimental tools, techniques, and data analytic approaches, all of which come together to open new perspectives on the field of neurobiology in C. elegans, and neuroscience in general. WIREs Syst Biol Med 2017, 9:e1376. doi: 10.1002/wsbm.1376 For further resources related to this article, please visit the WIREs website.

Novel Technological Advances in Functional Connectomics in C. elegans

“…This device was used to examine stimulus-response relationships in chemosensory neurons over a short temporal timescale [44]. Over the last decade, the applications of microfabrication techniques have exponentially increased in neuroscience with chips being designed for high-throughput and high resolution- based applications [44,45,46,47,48].…”

Functional Connectomics in <em>C. elegans</em>

“…The activity of a single neuron can be controlled by this method. Similarly, calcium imaging allows for the activity of a single neuron to be monitored (36). As in optogenetic studies, genetic manipulation is involved, but in this case using fluorescent tags such as GFP or mCherry fused to the calcium binding protein, calmodulin, resulting in Genetically Encoded Calcium Indicators (GECIs).…”

Multimodal Stimulation in a Microfluidic Device Facilitates Studies of Interneurons in Sensory Integration in C. elegans

“…Recent studies further demonstrate the advantages of microfluidics for automated and high‐throughput experiments when coupled with software and additional hardware . Further, microfluidics can be designed to work together with any modality of optical microscopy, allowing for the imaging of fluorescent markers such as calcium indicators …”

“…[28][29][30][31] Further, microfluidics can be designed to work together with any modality of optical microscopy, allowing for the imaging of fluorescent markers such as calcium indicators. [32] While microfluidic platforms have been widely developed for C. elegans to monitor neuronal activity and behavior under spatially or temporally controlled stimuli, including chemical, mechanical, oxygen, or temperature gradients, [32][33][34][35][36][37][38] simultaneously recording neuronal activity under well-controlled multimodal stimulation via for instance, calcium imaging, has not yet been shown. This is mainly due to the complexity of these experiments and the demands and constraints each experimental component places onto the integrated assay system.…”