BRAIN EAGER: Tagging the Genetic, Synaptic, and Network Origins of Learning from Social Experiences

University Of Texas Southwestern Medical Center, Dallas TX

Investigators

Abstract

How we learn from social experiences and during social interactions is poorly understood, but it is thought to involve intricate changes to nerve cells in the brain and the connections between these cells. Cells involved in social learning are intermingled and intertwined with cells that may have completely different functions. Because of this complexity, identifying and studying the specific cells and networks involved in social learning remain a major challenge, and new methods are required to address this needle-in-a-hay-stack problem. This research will build a new set of genetic tools that allow researchers to mark cells in the brains of mice and zebra finches that are specifically involved in learning during social interactions, and will apply cutting-edge imaging, physiological, and genetic methods to dissect how the marked cells change during learning. This research is of fundamental importance because it will shed light on the brain mechanisms involved in social learning and build a new set of genetic tools that can be used by the scientific community to study brain mechanisms involved in learning and memory. The research also is of importance because developmental disorders and head injuries can severely compromise circuits in the brain and individuals' ability to learn from social encounters and navigate complex social interactions. The tools and methodologies developed in this research will be made freely available to other scientists through the world-wide web (http://www.utsouthwestern.edu/education/medical-school/departments/neuroscience/index.html) and through the Addgene public repository (http://www.addgene.org/). Funding for this research will also be used to educate and train young scientists in novel genetic, molecular, imaging and behavioral methodologies. The proposed research will identify neuronal mechanisms involved in social learning from olfactory and auditory cues in mice and zebra finches, respectively. The proposal takes a highly interdisciplinary, collaborative approach involving four independent laboratories. The researchers will fluorescently "tag" neurons in mice and zebra finches that are selectively activated by olfactory and auditory social experiences using novel genetic strategies and viral tools that leverage the immediate-early gene c-Fos. Within brain regions of interest (olfactory and vocal learning circuits), these viral tools will differentially label neuronal populations depending on cellular activity and the specific social cues animals experience. In vivo Ca2+ imaging will be used to identify and map populations of neurons involved in processing and learning from social encounters. Novel optical methods will be used to map synaptic connectivity among tagged neuronal populations in vivo. Electrophysiological and transcriptomic analyses will be used to identify physiological and genetic factors unique to each tagged population, and identify neural subtypes and subpopulations responsible for social learning. These combined approaches will help reveal the network-level plasticity induced by social experiences. This collaborative, high-risk/high-impact research will generate novel in vivo molecular tools that allow fine and selective dissection of the network components of social learning.