Xenopus laevis is an extremely powerful system in which to study the genetics and biophysics of developmental morphogenesis. To allow the field to capitalize on the power of this model species for neurobehavioral work, we propose the creation of a new research tool: a computer-controlled system which enables the fully-automated analysis of behavior. The system consists of 200 individual chambers each containing a single Xenopus larva (or indeed, any of a number of small model species). The computer controls the light distribution, sound, and temperature environment within each dish, and continuously monitors the behavior of each animal. By providing changes in this environment, the system can not only observe and analyze the reactions of a large number of subjects in parallel, but also train the animals in a variety of classical conditioning and other learning paradigms. This system will enable researchers to study normal and genetically or pharmacologically-modified larvae and ascertain effects of any experimental perturbation on movement, learning rate, sensory perception, etc. We will design and create the system to maximize its adoption by as many labs as possible, and make publicly available detailed manuals for its construction and use. By creating a standardized, modular, fully-automated device and software, we will enable any lab to conduct powerful analyses of behavior. Moreover, any lab will be able to repeat another lab's work precisely, even if complex behavioral experiments are involved. This device also eliminates operator tedium and subjective interpretation inherent in manual experiments with animals, and provides completely objective metrics of many aspects of tadpole behavior. The data is saved as movies of each chamber and quantitative measurements in Excel, allowing any permitted person (even remotely, via the internet) to analyze the data. We further propose to use this device to study the behavior and learning ability of larvae with reversed brain asymmetry (altered handedness of brain hemispheres). Because of its ability to handle many animals simultaneously, this system will serve as an important proof-of-principle prototype for future efforts that will enable screening large drug and gene libraries for new compounds that enhance memory and learning, counteract neurotoxins or drug addiction, function as sedatives or stimulants, etc. Current screening efforts are done in simple unicellular models, which do not offer the ability to discover new drugs with important and beneficial neuroactive effects. The creation of this system and illustration of its use on an important neurobiological problem (the behavioral consequences of brain lateralization) will enable great progress in the fields of neuroscience, and will accelerate the discovery of drugs and gene products that have specific and desired effects on cognition, behavior, and memory. Our application is ideally suited to the goals of NIMH, since it is a unique tool for the automated study of the mechanisms linking nervous system structure and function.
This work will have high positive impact on public health by 1) providing a new tool to the research community for research into a number of cognitive and neural diseases, 2) shedding light on the consequences of brain laterality reversal for memory and learning, and 3) enabling identification of new drugs targeting brain disease and augmenting learning and memory abilities. These three outcomes will result in the eventual development of novel therapeutics for brain diseases.
| Blackiston, Douglas J; Levin, Michael (2013) Ectopic eyes outside the head in Xenopus tadpoles provide sensory data for light-mediated learning. J Exp Biol 216:1031-40 |
| Blackiston, Douglas J; Levin, Michael (2013) Inversion of left-right asymmetry alters performance of Xenopus tadpoles in nonlateralized cognitive tasks. Anim Behav 86:459-466 |
| Pai, Vaibhav P; Vandenberg, Laura N; Blackiston, Douglas et al. (2012) Neurally Derived Tissues in Xenopus laevis Embryos Exhibit a Consistent Bioelectrical Left-Right Asymmetry. Stem Cells Int 2012:353491 |
| Blackiston, Douglas J; Levin, Michael (2012) Aversive training methods in Xenopus laevis: general principles. Cold Spring Harb Protoc 2012: |
