Dual Color Neural Activation and Behavior Control with Chrimson and CoChR in Caenorhabditis elegans.

By enabling a tight control of cell excitation, optogenetics is a powerful approach to study the function of neurons and neural circuits. With its transparent body, a fully mapped nervous system, easily quantifiable behaviors and many available genetic tools, Caenorhabditis elegans is an extremely well-suited model to decipher the functioning logic of the nervous system with optogenetics. Our goal was to establish an efficient dual color optogenetic system for the independent excitation of different neurons in C. elegans. We combined two recently discovered channelrhodopsins: the red-light sensitive Chrimson from Chlamydomonas noctigama and the blue-light sensitive CoChR from Chloromonas oogama. Codon-optimized versions of Chrimson and CoChR were designed for C. elegans and expressed in different mechanosensory neurons. Freely moving animals produced robust behavioral responses to light stimuli of specific wavelengths. Since CoChR was five times more sensitive to blue light than the commonly used ChR2, we were able to use low blue light intensities producing no cross-activation of Chrimson. Thanks to these optogenetics tools, we revealed asymmetric cross-habituation effects between the gentle and harsh touch sensory motor pathways. Collectively, our results establish the Chrimson/CoChR pair as a potent tool for bimodal neural excitation in C. elegans and equip this genetic model organism for the next generation of in vivo optogenetic analyses.

The balance between cytoplasmic and nuclear CaM kinase-1 signaling controls the operating range of noxious heat avoidance.

Through encounters with predators, competitors, and noxious stimuli, animals have evolved defensive responses that minimize injury and are essential for survival. Physiological adaptation modulates the stimulus intensities that trigger such nocifensive behaviors, but the molecular networks that define their operating range are largely unknown. Here, we identify a gain-of-function allele of the cmk-1 CaMKI gene in C. elegans and show that loss of the regulatory domain of the CaMKI enzyme produces thermal analgesia and shifts the operating range for nocifensive heat avoidance to higher temperatures. Such analgesia depends on nuclear CMK-1 signaling, while cytoplasmic CMK-1 signaling lowers the threshold for thermal avoidance. CMK-1 acts downstream of heat detection in thermal receptor neurons and controls neuropeptide release. Our results establish CaMKI as a key regulator of the operating range for nocifensive behaviors and suggest strategies for producing thermal analgesia through the regulation of CaMKI-dependent signaling.

Dynamic switching between escape and avoidance regimes reduces Caenorhabditis elegans exposure to noxious heat.

To survive, animals need to minimize exposure to damaging agents. They can either stay away from noxious stimuli (defined as avoidance), requiring the detection of remote warning cues, or run away upon exposure to noxious stimuli (defined as escape). Here we combine behavioural quantitative analyses, simulations and genetics to determine how Caenorhabditis elegans minimizes exposure to noxious heat when navigating in thermogradients. We find that worms use both escape and avoidance strategies, each involving the modulation of multiple parameters like speed and the frequency of steering and withdrawal behaviours. As some behavioural parameters promote escape while impairing avoidance, and vice versa, worms need to dynamically tune those parameters according to temperature. Furthermore, selectively disrupting avoidance or escape, through mutations affecting neuropeptide or TRPV channel signalling, increases exposure to heat. We conclude that dynamically switching between avoidance and escape regimes along the innocuous-noxious temperature continuum efficiently minimizes exposure to noxious heat.