Comprehensive profiling of brain dynamics during anesthesia across phylogeny
Abstract
Abstract The behavioral effects of anesthetics are highly conserved across species, hinting at shared and fundamental underlying mechanisms. Here we compile a dataset of multiscale neural activity during wakefulness and anesthesia, encompassing human, macaque, marmoset, mouse, zebrafish and nematode. Applying massive feature extraction, we characterize local neural dynamics across >6,000 time-series features. This reveals a conserved dynamical profile of anesthesia across species, characterized by shorter intrinsic timescales of neural activity and dampened inter-regional synchrony. Deep-brain stimulation of the macaque centromedian thalamus reverses this profile and restores behavioral responsiveness. This conserved dynamical phenotype covaries with conserved transcriptional profiles of excitatory and inhibitory neurotransmission. Biophysical modeling provides a potential mechanistic link between the macroscale dynamical phenotype of anesthesia and microscale effects of key molecular targets on the timescales of synaptic excitation and inhibition. These analyses reveal a shared neural endpoint of anesthesia: across species and scales, anesthetics induce spatiotemporal isolation of local neural activity.
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Authors: Andrea I. Luppi, Lynn Uhrig, Jordy Tasserie, Golia Shafiei, Antoine Légaré, Kanako Muta, Junichi Hata, Hideyuki Okano, Daniel Golkowski, Andreas Ranft, Rüdiger Ilg, Denis Jordan, Silvia Gini, Zhen-Qi Liu, Yohan Yee, Pablo Castro, Camilo Miguel Signorelli, Rodrigo Cofré, Alain Destexhe, David Krishna Menon, Emmanuel Andreas Stamatakis, Patrick Desrosiers, Paul De Koninck, Christopher W. Connor, Alessandro Gozzi, Ben Fulcher, Béchir Jarraya, Bratislav Mišić
Institutions: Brigham and Women's Hospital, University of Pennsylvania, The University of Sydney, Harvard University, University of Oxford, Boston University, University of Calgary, University of Copenhagen, Inserm, Commissariat à l'Énergie Atomique et aux Énergies Alternatives, University Hospital Heidelberg, Université Paris Cité, Sorbonne Paris Cité, University of Cambridge, Centre National de la Recherche Scientifique, RIKEN Center for Brain Science, Université Laval, McGill University, Technical University of Munich, TUM Klinikum, Université Paris-Saclay, CEA Paris-Saclay, Italian Institute of Technology, University of Trento, Tokyo Metropolitan University, Keio University, Institut des Neurosciences Paris-Saclay, FHNW University of Applied Sciences and Arts Northwestern Switzerland, Institut de Physique de Nice, Hôpital Foch, Center for Neuroscience and Cognitive Systems, Asklepios