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Forsyth Scientists Develop System for Automated Analysis of Behavior


Computer-Controlled System Also Offers New Methodology for Rapid And Efficient Drug Screening

Tuesday, August 22, 2006 Boston The Forsyth Institute today announced the creation of a new computerized system for monitoring, analyzing and controlling cognitive science experiments. For the first time, researchers will have the ability to automate the analysis of animal behavior, while also conducting functional experiments on a large number of subjects simultaneously. The Forsyth Automated Training Apparatus, (ATA), also provides an efficient methodology to conduct drug screening and potentially shorten the development time for new drugs.

Michael Levin, Ph.D., Director of the Forsyth Center for Regenerative and Developmental Biology, and his team, use the flatworm, Planaria, to investigate biophysical control mechanisms in the study of regeneration and memory. They have also developed a number of techniques to manipulate the nervous system of embryonic frog and fish embryos, and are now investigating how behavior and memory is determined by central nervous system structure. The Levin Lab developed this computer-controlled system to overcome a number of problems that exist in current attempts to understand how the brain and nervous system give rise to memory, behavior, and cognition by studying animal model systems.

The challenges in studying animal behavior include:

· Large amounts of time needed to get statistically-meaningful data (having to watch an animal in detail over multiple 24-hour periods is often impractical and gives rise to operator tedium);

· observer bias and difficulty of objective, quantitative measurements of behavior and memory;

· oversensitization of subject animals from handling;

· inconsistencies in protocols and controls, making it difficult for other laboratories to repeat experiments and verify their results;

· difficulty in making primary data available to other groups in the field.

Previous efforts to automate behavioral experiments have primarily focused on larger animals such as rodents, worked with one animal at a time, and require a researcher to observe behavior. The system, developed by Levin and his colleagues, Caitlin Hicks and Debra Sorocco, is scaleable and allows researchers to overcome these challenges by allowing a large number of animals to be analyzed, with generation of primary data that is immediately inputted into a data base. The system also enables scientists to automate control of the environment – the software manipulates each animal’s sensory inputs and records many aspects of their reactions. By providing appropriate stimuli animals can be trained to move in certain ways based on light cues, allowing the study of learning and memory. Levin and his coworkers developed a standardized, modular platform that can easily be deployed in other labs, allowing any researcher to automatically and quantitatively compare behavior and learning performance in normal, or genetically- or pharmacologically-modified animals. An overview of the project will be published in the September issue of the Journal of Neurobiology.

“This automated technology opens up research in exciting directions,” said Dr. Levin. “The use of this system will reveal much about cognitive abilities of many different species, while simultaneously eliminating the margin of error. We are looking forward to sharing some of the results of our research with the neurobiology community.”

According to Philip Stashenko, D.M.D., PhD, Vice President of Research for The Forsyth Institute, the system also offers great potential for the pharmaceutical industry. “Dr. Levin’s prototype solves experimental problems in the lab today and offers a solution that will be very useful in the search for the neuromodulatory drugs of the future.”

Benefits to Drug Screening

A number of academic and commercial pharmaceutical projects have generated large genetic, proteomic, or small-molecule (drug) libraries that must be screened to identify compounds of interest to both biomedicine and basic biology. Typically this screening is conducted on single cells in culture, or in organisms such as yeast. However, these strategies are insufficient for studying the effect of compounds on complex multicellular systems or nervous system function. If one wants to find a drug that improves memory or works as a sedative, single-cell models are not informative. Screens on multicellular models, such as zebrafish, have been successful but the current necessity for manual analysis has made it impractical for high-throughput neurological screens.

The Forsyth system can be scaled to provide an extremely powerful tool by allowing automated screens in small animal model systems for new compounds that, for example increase learning and cognitive ability, expand memory, are sedatives or stimulants, counteract effects of neurotoxins, suppress pain, modulate the activity of other psychoactive compounds, or serve as antidotes to drug addiction.

How it Works

The device basically consists of a set of small chambers monitored by digital cameras. Each chamber contains a complex set of light, vibration, and other devices. The computer constantly monitors the animal’s position and orientation within each dish and provides rewards or noxious stimuli in accordance to the pre-established ‘learning’ program. For example, a worm may be rewarded with the turning off of a bright light whenever it stays in a small area at the center of the dish, thus training it to remain in a particular location. Or a tadpole may be trained to move for 5 seconds whenever a bright light is applied. The device makes it easy to designate some chambers as controls (where a random or opposite relationship between stimulus and response is given) and automatically produces both QuickTime digital movies of each animal’s chamber and a data file from which one can easily compute time spent in each area of the dish, average movement, etc. By running a given protocol in this device, a researcher can gather data for

many days without any involvement on their part, thus freeing up valuable time and removing sources of bias. Other labs are then able to analyze the data remotely (over the web) and mine it in any way they wish.

Michael Levin, PhD. is an Associate Member of the Staff in The Forsyth Institute Department of Cytokine Biology and the Director of the Forsyth Center for Regenerative and Developmental Biology. Through experimental approaches and mathematical modeling, Dr. Levin and his team examine the processes governing large-scale pattern formation and biological information storage during animal embryogenesis. The lab’s investigations are directed toward understanding the mechanisms of signaling between cells and tissues that allows a living system to reliably generate and maintain a complex morphology. The Levin team studies these processes in the context of embryonic development and regeneration, with a particular focus on the biophysics of cell behavior.

The Forsyth Institute is the world’s leading independent organization dedicated to scientific research and education in oral, craniofacial and related biomedical sciences.


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