Neural representation of mating partners by male C. elegans

项目总结

Project Summary Understanding how neural circuits create animal behavior requires knowing the system-wide activity patterns that connect sensory experience to motor activities, all within the full set of feedback loops by which actuated motor decisions modulate the animal's perceptions of itself and the outside world during naturally executed and unrestrained behaviors. Mechanistic understanding further requires interpretation of system-wide activity patterns in terms of the connectivity, synaptic, and cellular properties of all relevant neurons. Modeling requires comprehensive mapping of the salient dimensions of sensory input and motor output, as well as how high- dimensional neural activity patterns are properly projected, by decision-making and the internal constraints of the nervous system and motor system, into the fewer dimensions that characterize any animal's observed behavior. Such models are facilitated by using animals where entire brain and motor circuits can be mapped and interrogated with full molecular and cellular resolution. Here, we will use the mating behavior of the male C. elegans as such a paradigm. The mating behavior of C. elegans is a critically important and goal-directed task that occurs in natural environments and is robustly executed in the laboratory. Males use a specialized circuit of ~100 neurons – sensory neurons, interneurons, neuromodulatory, and motor neurons – all contained within the male tail ganglia to locate hermaphrodites, locate the vulva along the hermaphrodite's body, and initiate and complete insemination. A diverse set of mechanosensory, chemosensory, and pheromone sensing neurons are used to recognize the shape, texture, and chemical signature of the hermaphrodite body. Several neurons are specialized to detect fiducial points along the hermaphrodite body. The male implicitly uses an internal representation of the size, shape, and predictable behaviors of the hermaphrodite to positively recognize the hermaphrodite, infer its own position along the hermaphrodite, and execute an optimal movement strategy to maintain contact with the hermaphrodite and find and penetrate the vulva. It is now possible to record neural activity from the entire set of neurons in the male tail with high temporal resolution and complete cellular resolution. We will couple experiments, modern data analysis and modeling methods, and cellular and molecular genetic perturbations to elucidate the full set of sensorimotor events that organize the mating behavior. We will develop a realistic model of the circuit that integrates the observable behavioral algorithms with the connectivity and activity patterns of the male tail ganglion. We will apply genetic tools to identify and elucidate each sensory neuron type, and how it affects each aspect of decision-making by downstream interneurons and motor neurons. We will characterize key synaptic properties by molecular dissection of neurotransmitter and receptor types. We will store this comprehensive neurophysiological and neurogenetic data in online project databases connected to our computational models that will allow the wider community to view and probe our data-driven modeling eff ort.