Viscerosensory Modulation of Brain Circuits in Larval Zebrafish

Project Summary/Abstract How brain circuits are modulated by sensory signals from internal organs (viscera) during ethologically relevant behaviors is a fundamental, yet largely unexplored question in neuroscience. Achieving a comprehensive understanding of viscerosensory integration in the brain of unanesthetized animals has been challenging given that neural activity measurements in the vagus nerve, the main viscerosensory input to the brain, require invasive procedures in rodents. This project will address this challenge by using the zebrafish larva. Its suitability for organism-wide neural activity measurement and genetic manipulation, as well as its well- characterized behaviors, all make it an ideal system for a comprehensive systems-level investigation of viscerosensory integration in the brain during naturalistic behaviors. In the R34 phase of the grant, this project will focus on (1) probing visceral response dynamics like heart rate, gill ventilation, and gut motility in response to environmental challenges; and (2) determining the viscerosensory inputs to the brain by studying the encoding properties of vagal sensory neurons. Accomplishing Aims 1 and 2 would set the stage for investigating the neural circuits that integrate viscerosensory information in different brain regions and their role in behavior and decision-making. Aim 1: Determine internal organ dynamics in response to environmental changes. Aim 1 of the project will measure the changes in heart rate, gill ventilation, and gut motility in addition to tracking behavioral variables like tail angle and eye position during responses to visual threat, oxygen fluctuations, or temperature fluctuations. We will use machine learning techniques to identify discrete ‘visceral states’ from measured internal organ dynamics. Then behavioral and visceral states will be merged using multidimensional embedding techniques to identify discrete ‘organismal states’ and the transitions between them. Aim 2: Probe the encoding properties of vagal sensory neurons Aim 2 will measure neural activity in the right and left vagal sensory ganglia of behaving fish while also tracking the internal organ parameters described in aim 1. These datasets will be summarized using encoding models to describe the visceral information represented in each cell of each vagal ganglion.