New technologies that have made it possible to visualize specific classes of neurons, and to monitor and manipulate their activity in vivo, are transforming our understanding of neural circuit function and development. While the range of tools for molecular circuit visualization and manipulation continues to grow at an explosive rate in the mouse, the development of comparable tools for the study of circuits in non-murine mammals lags far behind. The inability to employ state of the art molecular tools for cell-type specific visualization and manipulation of neural circuits severely limits progress in understanding important aspects of cortical organization that are not well represented in the mouse brain. The goal of this application is to begin to bridge this technology gap by developing a recombinant viral vector for use in non-murine mammals that will permit in vivo expression of molecular reporters and effectors using cell-type specific promoters. As proof of principle, we will generate and characterize a helper-dependent adenovirus (HdAd) vector that will allow the selective expression of genetically encoded fluorescent proteins and light-sensitive channels in GABAergic neurons of the ferret visual cortex. The availability of a viral construct that yields expression selectively in GABAergic neurons of non-murine mammals will make it possible to address a host of questions that are critical for understanding cortical function in health and disease. Moreover, success in generating this construct will open the door to a battery of cell-type specific molecular tools that will be of tremendous value for the study of cortical and subcortical structures in a wide range of mammalian species including primates.
In this project we aim to develop new molecular tools that will allow us to analyze the structure, function, and development of identified populations of neurons in the living brain. The knowledge derived with these tools will provide the foundation for developing new approaches to the diagnosis and treatment of neurological and psychiatric disorders.