Thalamic regulation of prefrontal dynamics in decision making under uncertainty

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Abstract: Research Plan: Decision making is a process through which actions are selected based on sensory cues or value of desired outcome. Critical to their function decision making systems, like the prefrontal cortex (PFC), need to capture the causal structure of its environment (an internal model or belief system) and update its internal beliefs when underlying associations change. While a lot of effort has gone into understanding neural circuit mechanisms within the PFC recent findings suggest that interactions with the medio dorsal thalamus (MD) is crucial for its function and are especially important when decisions must be made using information that is noisy. Moreover, failure to resolve noise in updating internal beliefs is thought to underlie schizophrenia and related psychotic illnesses. Thus, determining the circuit mechanisms of MD-PFC interactions is relevant to not only cognitive neuroscience but also to psychiatry. This K99/R00 research proposal will address the role of MD in regulating PFC dynamics during decision making under uncertainty through the following three Aims. Aim 1, will explore if genetically identifiable populations within the MD, due to their unique connectivity with the PFC, are selectively geared towards resolving sensory input uncertainty arising from high noise versus low signal. Aim 2 will explore the role of MD in a multi-step decision making paradigm to study human-like reasoning using treeshrews (Tupaia), which are akin to basal primates. The first two Aims 2 will be carried out in the K99 training phase. In Aim 3, performed in the independent R00 phase the findings from Aim 1 and 2 will be extended to economic decision making where uncertainty exists at the level of expected rewards. These Aims collectively, will elucidate the circuit mechanisms through which the MD-PFC interactions play a role in resolving uncertainty in decisions and will further provide precise targets through which deficits in decision making can be therapeutically ameliorated. Career Development Plan: The K99 training will provide the tools and training necessary to study the activity of neurons in the brain to decipher underlying circuit mechanisms. The R00 phase will build the foundations of an independent research career driven by experiments that deconstructs complex decision making into a combination of simpler cognitive processes sub served by specified circuitry.