Mechanisms and Functions of Brain- Body- Environment Interactions in C. elegans

Descripción del proyecto

Comprensión de los mecanismos de control encefálico del comportamiento medioambiental

Las grabaciones de la actividad neuronal a gran escala han revelado que los patrones de actividad neuronal generalizados en todo el encéfalo codifican parámetros de movimiento. Las representaciones conductuales a nivel encefálico también están implicadas en el procesamiento sensorial. Estos hallazgos son universales en todo el reino animal, desde los nematodos hasta los mamíferos, pero los mecanismos subyacentes siguen sin conocerse. El equipo del proyecto elegansBrainBodyEnvi, financiado por el Consejo Europeo de Investigación, utilizará el nematodo «Caenorhabditis elegans» como modelo animal para aplicar una combinación de imágenes de Ca2+ de resolución unicelular en todo el encéfalo y manipulación genética en animales en libertad. El estudio en nematodos brinda la oportunidad de dilucidar las funciones universales de las representaciones conductuales de todo el encéfalo. El objetivo es establecer principios fundamentales y formular hipótesis de trabajo para futuros estudios en organismos modelo y encéfalos más complejos.

Objetivo

Recent large-scaRecent large-scale neuronal activity recordings in awake, behaving animals revealed a new, unexpected neuroscientific principle: widespread neuronal activity patterns across the brain encode parameters of movement. Surprisingly, these brain-wide behavior representations even extend to areas that are implicated in the processing of sensory information (e.g. the visual cortex in mice). Thus, a large fraction of the brains activity seems to be dedicated to representing the animals current, ongoing behavior. These observations have been made across the animal kingdom including worms, flies and mammals, suggesting a universal principle; however, the underlying mechanisms and functions remain unknown. In this proposal, we take advantage of the tractable model organism C. elegans to tackle this problem, combining brain-wide single cell resolution Ca2+-imaging in freely behaving animals with genetic circuit manipulation tools. It was previously recognized that the brain operates in a closed loop, actively sensing its body and its environment and making predictions of movement outcomes to optimally control behavior. Here, we propose to reconcile these long-standing concepts with the new observations of brain-wide behavior representations. Our core hypothesis is that sensory to motor transformation is a distributed process incorporating multiple functions like gain-control, re-afference prediction and predictive processing. Our team is at the forefront of scientific innovation and discoveries in this field, and we thereby are making substantial contributions to this currently ongoing paradigm shift in our understanding of how the brain operates. Studying these phenomena in worms offers a unique and timely opportunity to rapidly uncover the universal functions of brain wide behavioral representations. We therefore aim to make fundamental predictions and to formulate new working hypotheses for similar studies in larger model organisms with more complex brains.