Disturbance in neuronal circuits critical for mediating reward and aversion underlies a number of neuropsychiatric disorders. However, genes and pathways that control the assembly and function of the reward and aversion neuronal circuits remain poorly defined. In this exploratory R21 application, we propose to employ larval zebrafish to study neuronal circuits underlying aversion, because the system offers great opportunity for high throughput genetic and drug screening in the context of a developing vertebrate brain. We have discovered that larval zebrafish find the dark environment aversive thereby preferring to stay in the light side. Our central hypothesis is that this dark avoidance behavior represents an excellent paradigm for understanding the development of neuronal circuitry underlying aversion at molecular and cellular levels.
This project aims to advance our understanding of the aversion neural circuitry at molecular and cellular levels. These studies will bridge critical technological and knowledge gaps, and lay foundation for understanding human disorders such as addiction ad anxiety, and in the long run, enabling the development of more specific and efficacious therapies for these disorders.