My long term goal is to establish an independent research program aimed at understanding a question which is emerging as a central one in neurobiology: how regions of the brain work in concert at a macro-scale while each computing information locally at a microscale. Since my arrival in the laboratory of Dr. Buzsaki, I have focused my work on leveraging the unique technical expertise in high density neuronal population recordings to characterize the neuronal dynamics of the anterior thalamus. This ensemble of nuclei is an unexplored network hub of the brain, that relays and coordinates complex information flow between areas of the limbic system, which is known to be involved in navigation, emotions, decision making and long term memory formation. The multi-directional flow of information within neural network makes relating these to behavioral outcomes difficult to interpret. Thus, the immediate goal of this research is to simplify the poblem by investigating the neural network giving rise to the head direction signal, a basic behavioral signal, major nodes of which are the anterior thalamus and the hippocampal formation. During the K99 mentored phase of this proposal, I propose first to receive training in high density extracellular recordings and to apply this skillset by performing novel dua site high density recordings in the anterior thalamus and the hippocampal formation. I will examine at once 1) the micro-circuits dynamics within these regions 2) the macro-scale coordination between these regions and 3) the influence of macro-scale dynamics on microcircuit processing. Then, to further understand the directionality of information flow in this interconnected network, I would also add optogenetics tools to my armamentarium by gaining training in state-of-the art methods combining optogenetics and electrophysiology, as recently developed in Dr. Buzsaki's laboratory. I will thus examine the effects of silencing either "top-down" cortical feedback or "bottom-up" sub-cortical inputs to the thalamic cells. These skills will be crucial building blocks for future studies in my own laborator, in which I plan to further dissect and reconstruct the complex dynamics of how thalamic nuclei coordinate brain activity. The long-term career goals of this proposal are to enable me to successfully launch my own research team, to establish new collaborations, to train fellows and students, and to submit grant proposals to secure independent funding. I will thus engage in several career developmental activities to give me the keys to successfully launch my laboratory. Ultimately, this research will provide new insights onto the neuronal mechanisms allowing the emergence of cognitive processes. Unraveling the relationship between, even basic, cognitive processes and neuronal dynamics will take us one step further toward understanding the neural basis of psychiatric diseases such as in schizophrenia and other neurological disorders. Title of the proposal: Neuronal coordination in the thalamo-cortical head-direction system Specific Aims:
Aim 1 : Are HD cell ensembles between thalamus and cortex coordinated? Aim 2: How does perturbation of cortical and hypothalamic inputs affect thalamic HD cells?
Cognitive processes emerge from the collective activity of neuronal assemblies in large-scale brain networks, and unraveling the mechanisms underlying the communication between neuronal populations in various brain regions has become one of the central questions in neuroscience. The research goal of this proposal is to investigate the neuronal network dynamics giving rise to the internal representatin of head-direction, a critical piece of information for animals'navigation capabilities. Unraveling the relationship between, even basic, cognitive processes and neuronal dynamics will take us one step further toward understanding the neural basis of psychiatric disorders such as in schizophrenia and other neurological disorders.