Call for Interdisciplinary Projects Sevres A General Information

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1 Call for Interdisciplinary Projects Sevres 2014 Project title Impact of colors on Mice Behaviors A General Information Acronym ICMB Keywords (5) Colors perception, behavior, Cognitive, Comparative Biology, Chromo-therapy Team members Names Fields of interest Czerwinska Urszula Genetics, systems biology Marck Adrien Biology comparative, Cognitive sciences, sport, poetry, power rangers Marcou Quentin Image analysis, Pattern recognition, Machine learning Monnier Delphine Medicine, education Thouvenin Olivier Neurosciences, Imagery, Bioinspired materials Abstract (200 words max) It is widely approved that colors can impact human s moods and behavior. However there is a need for a solid quantitative basis to prove this statement. The vision disabilities are common disorders which make us address the question whether and how the multicolor environment would affect their behavior. Moreover, we are one step from the application for the gene therapy for colorblind people. It would be crucial to imagine the impact of such a therapy on their quality of life. In this study we will use three transgenic mice strains with different numbers of cone types (mono-, di-, tri-chromatic). Using an automated image analysis tool, we will analyze in a quantitative manner the different behaviors of these mice under exposure to different colors. With these lines we will make use of gene therapy to change the number of cone types during mice life. We will then analyze their changes in behavior in the way they behave. In parallel we will try to relate these behaviors to brain pattern activation using an innovative Doppler ultrasounds technique. 1

2 B Description of the project (1 page max) B-1 General Introduction Visual perception is one of the most important sense for human and other animals. Vision is involved in several primary tasks of life such as spatial displacement, predation, reproduction but also in more complex behaviors in social and cultural environments. The eye is a well structured organ possessing three types of photoreceptive cones (red, green and blue) in human and only two in mice (green and blue). The visual perception with these photoreceptors offers to animals a colored world. A previous study led by MA READ et al. has shown that colored walls of schools increases students cooperation. This previous research indicates that colors impact on behavior. The chromo-therapy appears as an alternative therapy for depression. Nevertheless, no studies have a holistic approach to understand how the perception of different colors impacts on the behavior of the animals. In this project, we propose to determine the difference in behavior in different colorful environment for the mice Mus musculus. In our colorful world, the color vision disorders might be a real handicap. The gene therapy aiming to cure the colorblindness have been already performed and proven in squirrel monkeys (ref). We are about to apply it in colorblind humans. But what would it mean to restore the full colorful vision of color disabled people? With the creation of mice strain with a trichromatic vision, there's a challenge how to cope the augmented skills. It is possible that one day we will be able to augment human vision with additional capacity. What would be the impact of our world perception and behavior. Would the meaning of colors change? Would our reaction change? As it has been tested that some animals have preference for different colors, we would like to test a quantify the behavior of four mice strains: WT (dichromatic), monochromatic (green or blue) and trichromatic (green, red, blue). We will make use of a high-tech devices and data treatment and modeling software. We would like to compare the behavior of mice with augmented, disabled and normal vision. At the same time, with the development of the gene therapy for monochromatic vision strain we address the question how the color perception abilities change can affect an individual. Therefore, this study will provide true quantitative data and provoke many ethic questions about the future world perception. B-2 Objectives and specific aims The project is an interdisciplinary research program based on the impact colors on mice behaviors. We will use different mice strains to determine the relation between color perception and behavior. Here we will test: (i): The relation between the number of type color cones and the behavior (ii): The change of number of cones during the life will impact on behavior (iii): Modulation of brain activation pattern 2

3 C Detailed description of the project (2 pages (max) + figures and references. The main scientific idea and aim should be developed, put into general context, and some details should be provided on the different phases and methodological approaches. Alternative routes should be proposed in the case of setbacks in the proposed plan. Ethical and/or safety aspects of the proposed research should also be discussed when identified) Colors are a vital element of the environment, for humans and for animals. The vision disabilities are widely recognized as a handicap. In few of years with gene therapy we will have treatment for color-blind and monochromatic people so we want know if it will change their behavior. In our project we will study impact of colors on mice behavior. We expect that changing color in environment can have an important impact. It is well know that colors are not negligible and animals can have a preference for a certain colors. However, we decided to measure rather their activity after exposure to a different color light. Moreover, inspired by recently created mice with trichromatic vision, we would like to investigate the colors effect on mice with mono-, di- and trichromatic vision. We are interested in the difference of reaction on a specific color and general behavioral change of mice strains. In the second experiment (i):for the first experiment we will use four groups of mice. The four groups are wild type (dichromatic vision: green, blue), human red pigment knock-in mouse (trichromatic vision) and two knock-out subgroups (monochromatic vision: green or blue) and will be ordered or bought from collaborating labs. Animals will be brewed in an animal housing in optimal conditions of food and temperatures. The four groups of animals (10-30 individuals each, with equal part of male and female) will be placed in boxes and illuminated with a specific color for a half a day. Mice behavior will be recorded with a digital camera. Mice should be of a similar age (1 year old). After a week in natural conditions we test a new light color to neutralize possible previous color effect. And we repeat that for the seven colors: red, green, blue, pink, yellow, UV-A and day light (for control). Collected data will be treated with appropriate software: Mice Profiler. (ii): The second part of the project aims at understanding if a change in the number of chromatic cone types during life will impact on mice behaviour. First, we will need to develop a gene therapy to modify the vision of mice during life. This therapy is based on viral vectors targeting mice cones photoreceptors inserting a gene coding for an opsin sensitive to a specific colour. The vectors will be injected directly on the retina, while the mice are anesthetized. Such an approach has already been proven successful in monkeys [Réf] and needs to be adapted in mice. We will develop three different vectors coding respectively for blue, green and red opsins. We will use two different strains of mice. First, we will use the previously studied monochromatic mice and restore a bi-chromatic vision at different ages (2 weeks, 1, 2, 6 and 12 months). Secondly, we will use a wild-type population of mice and apply this gene therapy to obtain mice with a tri-chromatic vision. Then, we will apply the same previous protocol to test the relation between colours and behaviour. So, we will test different ages for the gene therapy to precise previous results lead on dogs. (iii): In order to relate the global behaviour approach described previously and actual neurological processes we will study brain activation pattern arising from the behaviour changes. Eventually we will be able to identify brain regions involved in the attribution of an emotional valence attributed to different colours. To assess brain activation patterns, we will use an ultrasonic device mounted on the mice head. I has been demonstrated that Doppler ultrasounds allow to measure blood flow (similarly to BOLD signal measured by MRI), and thus determine activated regions in the brain [ref]. Control studies have already been conducted and demonstrated that the implantation of such a device has no influence on mice general behaviour (ESPCI neuroscience division). Hence we will be able to identify active areas of the 3

4 brain with a millimetric resolution in freely behaving mice. Alternatively, we would perform different behavioral tests like placing food in colored recipients and study the preference of different strains for a specific color. We would also test them in a maze with differently colored paths or in a water maze with colored rescue platforms. We would also increase the number of individuals or test for several age intervals. Our study also concerns about augmented vision abilities. Future would bring an application of gene therapy on colorblind humans. Data collected in our experiment would bring some insight of a change from dichromatic to trichromatic vision on their world perception. It also brings up a question of augmented human vision if we manage one day to enable human to see UV or IR light. Figure 2 : Proposal planning of the project. We will launch the experimental parts in parallel to have the time to improve the gene therapy technique. Delivrable - Scientific articles - Organization of a specific conference - Create a large network of collaborators and share the possible application. References: Komáromy, A. M., Alexander, J. J., Rowlan, J. S., Garcia, M. M., Chiodo, V. A., Kaya, A.,... & Aguirre, G. D. (2010). Gene therapy rescues cone function in congenital achromatopsia. Human molecular genetics, ddq136. Computerized video analysis of social interactions in mice. de Chaumont F 1, Coura RD, Serreau P, Cressant A, Chabout J, Granon S, Olivo-Marin JC. 4

5 D Scientific Interest in the project of all the participants and beyond (200 words max. What are your motivations to participate to this project? Why should other scientists, society and general public be interested?) Our team members come from various field: biology, physics, medicine, computer science and bioscience. This highly interdisciplinary project will require interactions from all these disciplines: synthetic biology, genetics, cognitive science, brain imaging, image analysis, and statistics. So our versatile team is perfectly suited to tackle this project. We have the unique opportunity to craft a cutting edge research project that will shed light on the behavioral aspects of color perception. We found many evidence that gene therapy could soon be applied to patients suffering from colorblind. While several teams work on developing treatments, we rather focus on the social outcomes of such a cure. On the other hand, it is important to have quantitative insights on the impact of colors. This data might be the starting point for further development of similar studies in human. Additionally, it would be proved evidence based for chromo-therapy. 5

6 E BUDGET (1 million euro max for 3 years including salaries, equipment, consumables, etc.) Salaries : 5 PH-D: euros Consommable : 150 mice (cages, technicians, food, ) : euros biology costs : others : Equipment : 150 mice : generously given echographe supersonicmagine : euros software : open source Bureautique : euros camera : euros Total : euros 6