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

Abstract

Animals' perception and behavior involve integration of multiple sensory modalities. Caenorhabditis elegans is a useful model for studying multimodal sensory integration, as it has well‐characterized neuronal circuits in a relatively simple nervous system. However, most studies based on functional imaging have only been conducted on single modal stimuli, because well‐controlled multimodal experiments for C. elegans are technically difficult. For instance, no single systems currently deliver precise stimuli with spatial, temporal, and intensity control, despite prior hypotheses that interneurons do integrate these sensory inputs to control behavior. Here, a microfluidic platform that can easily deliver spatially and temporally controlled combination stimuli to C. elegans is presented. With this platform, both sensory and interneuron activity is measured in response to mechanical and chemical stimulations in a quantitative and high‐throughput manner. It is found that the activity of command interneuron PVC can be modulated by prior stimulation both within the same and across different modalities. The roles of monoaminergic and peptidergic signaling are further examined on the process of multimodal integration through PVC activity. The approach exemplified here is envisioned to be broadly applicable in different contexts to elucidate underlying mechanisms and identify genes affecting multisensory integration.

Graphical-model framework for automated annotation of cell identities in dense cellular images

“… ( A ) Schematic of the microfluidic device Cho et al, 2020 used in chemical stimulation experiments. The position of nematode in the imaging channel is shown.…”

Graphical-Model Framework for Automated Annotation of Cell Identities in Dense Cellular Images

“…Isoamyl alcohol (IAA) is a well-known component of the bacterial metabolites that C. elegans senses and responds to 41–43 . We recorded neuronal responses to a step-change in IAA concentration using a microfluidic system 44 (Figure 4 – figure supplement 3). We observed both odor-specific responses and spontaneous activities (Figure 4E).…”

“…A) Schematic of the microfluidic device 44 used in chemical stimulation experiments. The position of nematode in the imaging channel is shown.…”

“…Whole-brain functional recording data while providing chemical stimulus were acquired using a microfluidic device designed for applying chemical stimulation 44 to the nose-tip of the animal. Here image stacks were acquired with 1 μm spacing between z-planes and 10 ms exposure for each z-plane.…”

On‐Chip Rotation of Caenorhabditis elegans Using Microfluidic Vortices

“…[18,19] Therefore, studies of C. elegans involving transgenic strains have been proven invaluable to the understanding of genetic and cellular mechanisms and the studies of human diseases. [20][21][22][23] Although C. elegans hermaphrodites possess a relatively compact nervous system (302 neurons) and 959 somatic cells organized into various tissues and organs, [20,24] clear and comprehensive observation of all cells can be difficult to image through conventional (i.e., widefield) microscopy, since distinct cells are sometimes challenging to resolve in worms lying on their side. Additionally, when using confocal microscopy at higher magnification, the quality of the fluorescent signals obtained in each z-slice decreases in intensity and resolution when imaging further away from the coverslip.…”