Deploying photons for communication within neuronal networks

Abstract

Deficiencies in neurotransmission lead to neurological disorders or misinterpretation of perceived threats. To restore defects in cellular communication, we developed a synthetic, photon-assisted synaptic transmission (PhAST) system. PhAST is based on luciferases and channelrhodopsins that enable the transmission of a neuronal state across space, using photons as neurotransmitters. We demonstrate the ability to overcome synaptic barriers and rescue the behavioral deficit of a genetically engineered glutamate mutant with conditional, Ca2+-triggered photon emission between two cognate neurons of the Caenorhabditis elegans nociceptive avoidance circuit.We also deploy these ingredients for asynaptic transmission between two unrelated cells in a sexually dimorphic neuronal network. Functional PhAST could sensitize otherwise poorly responsive males to touch and hence expand the behavioral repertoire. Our study, thus, establishes a powerful framework for complex photon-based communication between neurons in a living animal, that can readily be expanded to synthetic neuronal networks, organoids or non-invasive brain-machine interfaces.

Expanded FLP toolbox for spatiotemporal protein degradation and transcriptomic profiling in C. elegans

“…For generation of pBN532 hlh-12p::FLP::SL2::mTagBFP2, an intergenic gpd-2/-3 sequence was amplified with primers B1012 and B1364 (see Supplementary Table S1) using pBN338 as template. A sequence encoding mTag2BFP2 was amplified with B1365 and B1366 using pMINIT mTagBFP2 [31] as template. The two PCR fragments were PCR-stitched with primers B1012 and B1366 and inserted by NEBuilder HiFi DNA Assembly (New England Biolabs) into Mlu I of pBN523.…”

Sexually dimorphic architecture and function of a mechanosensory circuit in C. elegans

“…Analysis: Image processing and analysis were performed as described in 19 . To extract GCaMP intensity over time, images were preprocessed in ImageJ and then imported into python to extract signal intensity using in-house procedures written in Python or IgroPro.…”

“…Numerous studies have focused on understanding the molecular and cellular pathways involved in mechanosensation in both mammalian and invertebrate systems [12][13][14] . Although recent evidence has provided insight into sex differences in mechanical nociception [15][16][17][18][19] , it is still unknown whether males and females sense innocuous touch differently.C. elegans has been used extensively to explore the cells and molecules that govern mechanosensation, and specifically touch sensation 14,20 .…”

Sexually dimorphic architecture and function of a mechanosensory circuit in C. elegans

“…The stimulus pro le consisted of a 2-second 250 kPa pressure step, overlayed with a 150 kPa oscillation, resulting in a maximum de ection of 9 µm (Supplementary Figure S6C). Analysis: Image processing and analysis were performed as described in 19 . To extract GCaMP intensity over time, images were preprocessed in ImageJ and then imported into python to extract signal intensity using in-house procedures written in Python or IgroPro.…”

“…Numerous studies have focused on understanding the molecular and cellular pathways involved in mechanosensation in both mammalian and invertebrate systems [12][13][14] . Although recent evidence has provided insight into sex differences in mechanical nociception [15][16][17][18][19] , it is still unknown whether males and females sense innocuous touch differently.…”