Unraveling VTA modulation of hippocampal encoding

Louisiana State University, Baton Rouge LA

Investigators

Abstract

This award is funded in whole or in part under the American Rescue Plan Act of 2021 (Public Law 117-2). The brain is an organ that stores, compares, and interprets information about the state of the body, and how organisms interact with their environment. There is a wealth of information about objects, time, space, and events available to the organism. However, the storage capacity of the brain, and the volume of information that can be processed – at once – is limited. For this reason, there is a need for the brain to assign priority levels to environmental stimuli and select what is most applicable at a given time point. This mechanism and connections between the brain regions of the brain that controls it are still poorly understood. This research will investigate how two key brain regions concerned with novelty detection work together to continuously classify and prioritize the information to be stored in a continuously changing environment. This research will have a broad impact on society by increasing our knowledge and understanding of cognition in normal states. This research will further have broader impacts by elucidating the role of specific cell types in learning, and how their dysregulation can lead to neurological disorders. Lastly, this research is designed to increase participation in STEM by facilitating the training of students in cutting-edge techniques that can be applied broadly in biomedical science research and industries. Reciprocal connection between the VTA and hippocampus (CA1) forms a loop that governs novelty detection. While the VTA contains dopamine, glutamate, and GABA neurons, the function of the loop has been primarily attributed to the VTA dopamine projections. The goal of this research is to dissect the functional significance of VTA glutamate projections to the hippocampus, and their role in novelty learning and context discrimination. To achieve this goal, neural recording will be combined with optogenetic modulation of VTA terminals in the CA1 of freely behaving mice. This method will create the premise to address two main objectives; (1) Determine the function of the VTA-CA1 tract in CA1 integration of working memory and context. (2) Ascertain the role of VTA presynaptic inputs in CA1 pyramidal cell-interneuron synchrony. This research will fill gaps in the knowledge and understanding of neural circuits that govern novelty learning and context discrimination behavior. Cutting-edge genetic and electronic tools will be deployed to target and modulate VTA terminals in the CA1 of mice during behavioral tasks. Performing these experiments will significantly increase the understanding of cell-specific projections within the VTA-hippocampus loop. It will also elucidate the function of cell-specific neural circuits that have been overlooked by a traditional focus on VTA dopamine projections. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.