Johns Hopkins School of Medicine

Neural circuits for context, learning, and decision-making

Humans and other animals have a remarkable ability to flexibly adjust their actions based on external stimuli, environmental context and internal brain state. How does context influence learning and the expression of underlying knowledge? Some context-dependent responses may be maladaptive; for example, anxiety may repress the recollection of information under stressful conditions. Others may be adaptive, enabling discretion and choice in the face of risk or opportunity. More broadly, contextual factors, related to brain state and cost-benefit calculations, weigh on behavioral decisions and impact the interpretation of self-reported knowledge. Thus, it is crucial to disambiguate the effects of context from knowledge when interpreting performance.

My lab studies the neural circuits and dynamics that enable learning, with an emphasis on the role of context and brain state. We first aim to gain behavioral control by designing parametric behavioral assays. We then apply the modern tools of neuroscience to monitor, manipulate and model neural networks. We can monitor outputs with two-photon calcium imaging and measure synaptic inputs with whole-cell voltage clamp recordings. We manipulate networks with opto- and chemo-genetics, using pseudorabies techniques to target defined functional populations. Finally, we collaborate with theoreticians to develop testable hypotheses to constrain our interpretations of the ever-growing "big data" we collect. 

We also intend to apply insights from neural circuit research to disease states. In Alzheimer’s disease (AD), for example, familiar contexts can trigger episodes of lucidity even when patients are deep in cognitive decline. AD may impinge on the learning processes we study, but in reverse. Knowledge may exist in the AD brain but become inaccessible. Can this ‘hidden’ knowledge be unlocked? These momentary retrievals may reflect activation of context-dependent mechanisms and could be ripe for therapeutic intervention to improve cognition. More generally, neuroscience research that introduces a robust dialectic between the study of healthy and diseased cognitive states will undoubtedly reveal deeper insights into both.