On-chip functional neuroimaging with mechanical stimulation inCaenorhabditis eleganslarvae for studying development and neural circuits

Abstract

New designs of microfluidic devices can facilitate recording of C. elegans larvae neuronal responses to precise mechanical stimuli, which reveal new understanding of development of mechanosensory neurons and circuits.

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

“…We developed a monolithic microfluidic platform in which we can deliver chemical and mechanical stimulations to specific spatial locations of a worm body (Figure B,C; Figure S1, Supporting Information; see the Experimental Section for details). This device integrates PDMS actuators for the delivery of mechanical stimulus, with a chemical delivery module. Using the platform, we can touch either the anterior or posterior regions of the worm body and deliver chemical stimuli to either the head or tail of the worm (Figure A).…”

“…Our system can deliver simultaneous mechanical and chemical stimuli to C. elegans with precise spatiotemporal and intensity patterns, while recording single‐cell neuronal responses via calcium imaging. Specifically, we integrated deformable polydimethylsiloxane (PDMS) membranes that can deliver well‐controlled mechanical stimuli with a module for the controlled delivery of chemical stimuli via off‐chip solenoid valves. We demonstrate that both sensory neurons and interneurons can be activated by distinct types of stimulation.…”

Microfluidics for mechanobiology of model organisms

“…The use of microfluidics for mechanobiology of worms is largely limited to studies of sensory neurons in adults rather than in developing larvae. To our knowledge, Cho et al (2018) published the only device for testing touch sensitivity of larvae.…”

“…To study touch sensitivity of C. elegans larvae, Cho et al (2018) presented a device adapted from previous devices for studying adult worms (Cho et al, 2017; Nekimken, Fehlauer, et al, 2017), with a fluorescent calcium sensor, GCaMP (Chen et al, 2013), as a readout for neuron activation. To mechanically stimulate a worm, the authors used actuators similar to those described in Section 3, but required a different polymer formulation, resulting in a lower modulus of elasticity to enable actuation suitable for small larvae.…”

“…To mechanically stimulate a worm, the authors used actuators similar to those described in Section 3, but required a different polymer formulation, resulting in a lower modulus of elasticity to enable actuation suitable for small larvae. With this device, Cho et al (2018) showed that the anterior ventral touch neuron can still be activated, despite the fact that the neuron is not incorporated into downstream neuronal circuits at the L2 stage. Similarly, a harsh touch neuron can be activated in L2 larvae even before its branched structure forms.…”