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My lab studies how organisms adapt to an unpredictable environment using electrophysiology and optogenetics in behaving, head-fixed rats on a treadmill. Many psychiatric disorders are associated with an inability to adapt. An understanding of why this happens must start with basic research into neural circuits and cell types. To those ends, we have established a rat paradigm that is analogous to a clinical task for studying adaptive learning, called attentional set-shifting. Using this task, we address a number of basic questions about how frontal-neuromodulatory neuronal interactions control cognitive functions involved in set-shifting. In particular, we are investigating the activity of noradrenergic locus coeruleus (LC) cell type-specific ensembles (recently reported in Totah, et al. 2018 Neuron 99(5):1055-1068). We also focus on how each individual’s neurobiology affects their unique approach to adaptively solving problems. A second line of research is focused on the cellular basis of learning from mistakes. I will show that our head-fixed, treadmill-based task permits measurement of rats detecting a mistake and subsequently correcting it before crossing an error response threshold. This behavior is combined with single unit recordings and axonal tracing in the anterior cingulate cortex (ACC) and prelimbic division of the prefrontal cortex to resolve a long-standing debate regarding how the ACC detects errors to support adaptive behavior. Finally, I will present our plans to activate the LC using whole-body 460-480nm (blue) light transmitted to LC via the retina, which is already known to increase LC-associated signs of arousal and autonomic activity but lacks LC recordings as proof of activation by blue light. We are measuring the appropriate “dose” of blue light to activate the LC and improve behavioral adaptability.
