Nicoletti, Martina et al. (2021) International Worm Meeting "Biophysical models of C.elegans neurons: the case of AWCON and RMD neurons."

Folli, Viola, Nicoletti, Martina, Filippi, Simonetta, Ruocco, Giancarlo, Loppini, Alessandro, Chiodo, Letizia

[International Worm Meeting, 2021]

Caenorhabditis elegans nervous system constitutes an ideal framework for computational neuroscience studies. Its nervous system has been fully reconstructed in neuron numbers and connections. However, the mechanisms at the basis of neuronal signals generation in single neurons are still largely unexplored due to experimental difficulties related to the small size of the neurons. In this context, biophysical models of single neurons could help elucidate the single-neuron dynamics and guide future experiments. In this work, we present biophysical models of the ionic currents found in the nematode neurons and muscles, based on the application of the Hodgkin-Huxley model to the C. elegans case. The models of single ionic currents are combined to describe the dynamics of the AWCON sensory neurons and RMD motor neurons [1]. Our models properly replicate experimental voltage-clamp recordings on AWCON neurons and current-clamp recordings on RMD neurons. The role of single ionic currents in the whole-neuron dynamics is investigated by analyzing the conductance and the responses of in silico knockout neurons. These analyses highlighted the importance of T-type calcium currents and leakage currents in the peculiar bistable behavior observed in RMD neurons. Moreover, our analysis highlighted different dynamical regimes in C. elegans neurons, including bistable and sustained oscillatory regimes. Furthermore, we study the chemosensory responses of AWCON neurons in a wide range of odor concentrations and exposure times by coupling our model of the electrical responses [1] with the model of chemosensory responses developed by Usuyama et al. [2,3]. In conclusion, our work constitutes the basis for extensive biophysical modeling of the C. elegans nervous system from the single-cell up to network scale. [1] M. Nicoletti et al. PloS One 2019, 14(7): e0218738. [2] M. Usuyama et al. PloS One 2012, 7(8): e42907. [3] M. Nicoletti, et al. "AWC C. elegans neuron: A biological sensor model." 2020 IEEE International Workshop on Metrology for Industry 4.0 & IoT, Roma, Italy, 2020, pp. 329-333, doi:0.1109/MetroInd4.0IoT48571.2020.9138174

Lanza, Enrico et al. (2021) International Worm Meeting "C. elegans-based chemosensation strategy for the early detection of cancer metabolites in urine samples"

Folli, Viola, Ferrarese, Giuseppe, Caprini, Davide, Lonardo, Maria Teresa, Pannone, Luca, Ruocco, Giancarlo, Di Rocco, Martina, Martinelli, Simone, Schwartz, Silvia, Milanetti, Edoardo, Lanza, Enrico

[International Worm Meeting, 2021]

Olfaction is one of the primary mechanisms through which many animals adapt to environmental changes. Olfactory receptors, which in all animals belong to the G-protein coupled receptors (GPCRs) family, play a crucial role in distinguishing the wide range of volatile or soluble molecules by directly binding them with high accuracy. Chemosensation is particularly developed in organisms lacking long-range sensory mechanisms like hearing and vision. The genome of the nematode Caenorhabditis elegans possesses a remarkable number of genes encoding chemosensory receptors, making it able to detect a similar number of odorants as mammals, despite the extremely low number of chemosensory neurons available. Here, we show that C. elegans displays attraction towards urine samples collected from women with breast cancer but avoids those from healthy subjects. This behavior is strongly influenced by the female hormone cycle. Behavioral assays performed on animals in which the AWC sensory neurons were genetically ablated demonstrate an essential role of these neurons in sensing cancer odorants. Calcium imaging experiments on AWC neurons dramatically increase the accuracy in discriminating between positive and control samples (with an accuracy of 97.22%). Also, chemotaxis assays performed on mutant animals harboring individual deletion in genes encoding GPCRs expressed in AWC neurons allow us to identify candidate receptors that are likely to be involved in binding cancer metabolites. This finding suggests that a specific alteration of a restricted number of metabolites is sufficient for the highly accurate cancer discriminating behavior of C. elegans, which may allow in principle to identify the fundamental fingerprint of breast cancer.