Optogenetic Manipulation of Olfactory Responses in Transgenic Zebrafish: A Neurobiological and Behavioral Study.

Yun-Mi Jeong,Jeong-Soo Lee,Robert Gerlai,Cheol-Hee Kim,Kyu-Seok Hwang,Tae-Ik Choi

doi:10.3390/ijms22137191

Abstract

Olfaction is an important neural system for survival and fundamental behaviors such as predator avoidance, food finding, memory formation, reproduction, and social communication. However, the neural circuits and pathways associated with the olfactory system in various behaviors are not fully understood. Recent advances in optogenetics, high-resolution in vivo imaging, and reconstructions of neuronal circuits have created new opportunities to understand such neural circuits. Here, we generated a transgenic zebrafish to manipulate olfactory signal optically, expressing the Channelrhodopsin (ChR2) under the control of the olfactory specific promoter, omp. We observed light-induced neuronal activity of olfactory system in the transgenic fish by examining c-fos expression, and a calcium indicator suggesting that blue light stimulation caused activation of olfactory neurons in a non-invasive manner. To examine whether the photo-activation of olfactory sensory neurons affect behavior of zebrafish larvae, we devised a behavioral choice paradigm and tested how zebrafish larvae choose between two conflicting sensory cues, an aversive odor or the naturally preferred phototaxis. We found that when the conflicting cues (the preferred light and aversive odor) were presented together simultaneously, zebrafish larvae swam away from the aversive odor. However, the transgenic fish with photo-activation were insensitive to the aversive odor and exhibited olfactory desensitization upon optical stimulation of ChR2. These results show that an aversive olfactory stimulus can override phototaxis, and that olfaction is important in decision making in zebrafish. This new transgenic model will be useful for the analysis of olfaction related behaviors and for the dissection of underlying neural circuits.

Highlights

Multimodal integration of various sensory information in the environment is important to generate appropriate behavioral responses
The transgenic zebrafish were insensitive to the aversive odorant when stimulated by the ChR2 specific blue light. These results suggest that olfaction is a critical sensory input in decision making in wild type larval zebrafish as it is able to override phototaxis, an olfaction driven response that is abolished in transgenic fish upon optogenetic activation of the olfactory sensory neurons with the ChR2 specific blue light
Optogenetic methods allow activation/deactivation of specified neuronal subpopulations and the monitoring of neuronal activity in the intact brain, methods that help us understand how changes in the activity of specific neuronal circuits contribute to behavior

Summary

Introduction

Multimodal integration of various sensory information in the environment is important to generate appropriate behavioral responses. How the brain transforms sensory information into an observable behavioral output, i.e., how a decision is made to respond to a stimulus, is a major question in neuroscience. When two sensory inputs conflict, one sensory influence the other and this dominance may be beneficial in decision making of animals [1]. When incompatible sensory inputs such as an attractive and an aversive cue were given concurrently, which cue would be dominance and the underlying mechanism remains unclear. Olfaction (i.e., sense of smell) is one of the most important senses affecting decision making for survival and fundamental behaviors of animals [3]

Methods

Results

Conclusion