Bioelectronics for Millimeter-Sized Model Organisms

Abstract

Advances in microfabrication technologies and biomaterials have enabled a growing class of electronic devices that can stimulate and record bioelectronic signals. Many of these devices have been developed for humans or vertebrate animals, where miniaturization allows for implantation within the body. There are, however, another class of bioelectronic interfaces that exploit microfabrication and nanoelectronics to record signals from tiny, millimeter-sized organisms. In these cases, rather than implanting a device inside an animal, animals themselves are loaded in large numbers into bioelectronic devices for neural circuit and behavioral interrogation. These scalable interfaces provide platforms to develop new therapeutics as well as better understand basic principles of bioelectronic communication, neuroscience, and behavior. Here we review recent progress in these bioelectronic technologies and describe how they can complement on-chip optical, mechanical, and chemical interrogation methods to achieve high-throughput, multimodal studies of millimeter-sized small animals. ADVANTAGES OF MILLIMETER-SIZED ORGANISMS Small model organisms such as Caenorhabditis elegans, Drosophila, and zebrafish have been a cornerstone for understanding principles of neurobiology, behavior, genetics, and development (Davis, 2004; Sattelle and Buckingham, 2006; Stewart et al., 2014). Despite their small nervous systems and less anatomical complexity compared with that of mammalian models, there are significant advantages in using millimeter-sized animals to answer fundamental questions in neurobiology (Figure 1).

Multiple neuronal networks coordinate Hydra mechanosensory behavior

“…Transparent, millimeter-sized animals in particular offer a number of advantages for neuroscientists because it is possible to image neural activity throughout the entire nervous system using genetically encoded calcium or voltage-sensitive fluorescent proteins ( Broussard et al, 2014 ; Chen et al, 2013 ; Lemon et al, 2015 ; Prevedel et al, 2014 ; Ahrens et al, 2013 ; Cong et al, 2017 ; Kim et al, 2017 ; Portugues et al, 2014 ; Vladimirov et al, 2014 ; Gonzales et al, 2020 ). In addition, some millimeter-sized animals are compatible with microfluidic devices for precise environmental control and microscopy techniques that offer cellular-resolution functional imaging of the entire nervous system.…”

Multiple neuronal networks coordinate Hydra mechanosensory behavior

“…Transparent, millimeter-sized animals in particular offer a number of advantages for neuroscientists because it is possible to image neural activity throughout the entire nervous system using genetically-encoded calcium or voltage-sensitive fluorescent proteins [16][17][18][19][20][21][22][23][24][25] . In addition, some millimeter-sized animals are compatible with microfluidic devices for precise environmental control and microscopy techniques that offer cellular-resolution functional imaging of the entire nervous system.…”

In vivo neuromodulation of animal behavior with organic semiconducting oligomers

“…A major obstacle for the discovery of neuroactive compounds is the inability to predict how small molecules will alter complex behaviors. Behavioral profiling in simple animal models may reveal conserved functions of bioactive molecules and predict the mechanisms of action of compounds designed for other purposes ( 11 ). The small freshwater polyp Hydra vulgaris is an attractive animal model for neuromodulation because of its limited behavioral capacity, simple body anatomy, transparency and plasticity of the epithelia, and a nervous system with hundred to thousand neurons (depending on the animal size).…”