Cooperative Agreements

 DESCRIPTION (provided by applicant): Neurons communicate information through fluctuations in the electrical potentials across their cellular membranes. Whole-cell patch clamping, the gold standard technique for measuring these fluctuations, is something of an art form, requiring great skill to perform on only a few cells per day. Thus, it has been primarily limited to in vitro experiments, a few in vivo experiments, and very limited applications in the awake brain. Dr. Forest (and collaborator Dr.

 DESCRIPTION (provided by applicant): Genetic tools have dramatically increased the power and resolution of neuroscientific experiments, allowing monitoring and perturbation of specific neuronal populations within the brain, often in the context of complex cognitive and behavioral paradigms. However, the usefulness of these tools is limited by the available means of delivering them in circuit-specific ways, a major drawback in view of the critical importance of specific connectivity between individual neurons and between neuronal classes.

 DESCRIPTION (provided by applicant): The brain circuit is an intricately interconnected network of a vast number of neurons with diverse molecular, anatomical and physiological properties. Neuronal cell types are fundamental building blocks of neural circuits. To understand the principles of information processing in the brain circuit, it is essential to have a systematic understanding of the common and unique properties for each of its components - the cell types, how they are connected to each other, and what are their functions in the circuit.

 DESCRIPTION (provided by applicant): Our understanding of brain function at the cellular and circuit level is critically dependent on the ability to interrogate and alter neural cells withhigh specificity. The use of light, either through single-photon or multi- photon excitation, is the onl method that provides sufficient resolution to probe the brain at the cellular and subcellular levels.

 DESCRIPTION (provided by applicant): The human brain is arguably the most complex biological structure. Understanding how many different cell types exist in the human brain and mapping neural connections are critical tasks to better understand the development and function of the brain. This is particularly challenging in the human brain due to inherent limitations of working with postmortem tissue.

 DESCRIPTION (provided by applicant): Dramatic new insights into the functioning of neural networks have been made possible by our ability to visualize neural function with calcium-sensitive fluorophores, and biology has been revolutionized by the ability to sequence and manipulate DNA, RNA, and proteins. Both of these tremendous advances have unexplored "flip sides". Our understanding of neural network function remains limited by our inability see GABA-mediated synaptic activity: we can't measure the output of the remarkable diversity of interneuron structure and function.

 DESCRIPTION (provided by applicant):Unraveling the complexity of the mammalian brain is one of the most challenging problems in biology today. A major goal of neuroscience is to understand how circuits of neurons and non-neuronal cells process sensory information, generate movement, and subserve memory, emotion and cognition. Elucidating the properties of neural circuits requires an understanding of the cell types that comprise these circuits and their roles in processing and integrating information.

 DESCRIPTION (provided by applicant): Understanding the exact cell-type composition in brain regions is fundamental to integrating physiological, behavioral and neurochemical data to systematically understand the brain structure and function. At present, although the major categories of cell-types present in brain have been defined, the different subtypes within these categories, as well as their location and connectivity are far from understood.

 DESCRIPTION (provided by applicant): The classification of neurons into distinct types is a fundamental endeavor in neuroscience. Neuronal classification allows one to gain insight into the building blocks of the nervous system, is essential for a mechanistic understanding of the function of the nervous system and is a prerequisite for unambiguous communication between investigators. No single unequivocal categorization scheme exists yet for neurons in the mammalian cerebral cortex.

 DESCRIPTION (provided by applicant): Cajal revolutionized the study of the brain through the use of the Golgi stain to label cells sparsely and stochastically in a fashion that revealed a neuron's morphology in its entirety. Although genetic tools for sparse and stochastic labeling and manipulation of single neurons in Drosophila have been used extensively over the past 15 years, they have only recently become available for mammalian systems, but the latter tools are limited to only a few systems for which cell-type specific reagents (e.g.