Development and commercialization of optimal microscopes for membrane potential optical recording – Voltimagmicro

The understanding of the brain relies on the analysis of electrical and chemical activity from multiple sites of neurons, in particular those sites where synaptic signals originate. This concept also applies to the study of functional deficits in animal models with the ultimate goal of understanding the mechanisms of human diseases involving synaptic activity. To this purpose, optical techniques are unique in allowing recording of chemical and electrical signals from multiple neuronal structures at micron and sub-micron scale. The achievement of this type of measurements, however, often relies on the solution of very challenging technical problems, i.e. on the optimization of the optical apparatus which is typically available in very few laboratories. In contrast, the optical facilities available in several institutes and based on equipment from large manufacturers, do not provide enough flexibility for experiments of this kind. These factors prevent the important diffusion of optical measurements of membrane potential. To overcome these obstacles and satisfy the needs of this important market niche, a product that is both flexible for a particular experimental investigation and feasible for the research budget of individual research groups can be commercialized, under a licence agreement, by a small company with a long history in this type of product and service. Based on the expertise of Marco Canepari and Jean-Claude Vial, this proposal is aimed at designing and developing imaging systems for voltage imaging experiments with the ultimate goal of their commercialization. We choose as industrial partner CAIRN Research Ltd, a well established company in the fields of neurobiology and cardiology, because of its long history in customizing microscopy solutions. This project is timing because of the recent solution of technical problems related to voltage imaging experiments. In particular the dramatic improvement in the resolution of these measurements and the limitation of the problem of photo-toxicity opens the gate to the spread of these methods for pre-medical imaging. The coordinator of this project is an international leader in the field of voltage imaging and he is the editor of the first handbook of this technique. To satisfy the particular needs of potential customers, our commercial system will be developed starting from two prototypes: A) a two-photon microscope to resolve voltage signals from sub-micron structures and B) a microscope to combine voltage imaging with other optical techniques to correlate in space and time membrane potential and chemical signals. We designed a strategy to assess the capabilities of our system. We will make our prototypes available to external scientists selected as “potential customers”, to obtain an important feedback necessary for commercialization. Finally, we will provide variants of our system, tailored to the needs and budget of different experimentalists.