Chemogenetic manipulation of zebrafish brain
My laboratory investigates how animals process sensory information, and how different brain areas contribute to the sensory computation and sensory cue mediated behavior. Here, we propose to utilize the chemogenetic methods, as well pharmacology and genetics, which allows to perturb the activity of specific cells in the brain noninvasively. We will combined this method together with neural activity imaging and behavioral analyses.
We will use two chemogenetic tools: genetically engineered genes nitroreductase and TRPV1. Both these tools allow manipulation of neural activity and assess the role specific neuronal population in the brain in sensory processing and behavior. This also allows us to study the effect of perturbation of neural activity during different developmental stages on behaviour of animals and brain function. We expect to perform our experiments in a total 5760 zebrafish at different developmental stage from larvae to juveniles and adults. This experimental tool is noninvasive in zebrafish, does not involve chronic pain or invasive surgery. Our animals’ health is at most important for all these behavioral experiments.
Using zebrafish, a small vertebrate, we replace mammalian animal models such as the mouse or rats. Moreover, we refine the concentration of the chemogenetic drugs and duration of exposure to the drug and reduce the time of experiments to a minimal level. All our experiments consider studying the information processing of the vertebrate brain. Hence, these experiments require working with living animals. In the future, when enough information is collected, such experiments will be used to design computational models/simulations of brain circuits. This will allow reduction of the number of animals for such behavioral experiments.
We anticipate that our findings will go beyond zebrafish brain and will allow better understanding of neural mechanisms underlying psychological conditions such as learning disabilities, anxiety and inspire novel therapies.
We will use two chemogenetic tools: genetically engineered genes nitroreductase and TRPV1. Both these tools allow manipulation of neural activity and assess the role specific neuronal population in the brain in sensory processing and behavior. This also allows us to study the effect of perturbation of neural activity during different developmental stages on behaviour of animals and brain function. We expect to perform our experiments in a total 5760 zebrafish at different developmental stage from larvae to juveniles and adults. This experimental tool is noninvasive in zebrafish, does not involve chronic pain or invasive surgery. Our animals’ health is at most important for all these behavioral experiments.
Using zebrafish, a small vertebrate, we replace mammalian animal models such as the mouse or rats. Moreover, we refine the concentration of the chemogenetic drugs and duration of exposure to the drug and reduce the time of experiments to a minimal level. All our experiments consider studying the information processing of the vertebrate brain. Hence, these experiments require working with living animals. In the future, when enough information is collected, such experiments will be used to design computational models/simulations of brain circuits. This will allow reduction of the number of animals for such behavioral experiments.
We anticipate that our findings will go beyond zebrafish brain and will allow better understanding of neural mechanisms underlying psychological conditions such as learning disabilities, anxiety and inspire novel therapies.