Abstract
Cognitive flexibility, the ability to rapidly switch our thinking and actions according to context, is a fundamental component of higher cognition. Training animals to perform tasks requiring context-dependent evidence accumulation (Mante et al., 2013) provides a powerful method to investigate the neural substrates of flexible behavior, but the long time required to train animals poses severe limitations on the experiments that can be performed. In addition, while flexible behavior is disrupted in many neurodevelopmental disorders, these tasks have traditionally only been studied in primates, and are not available in animal models of genetic disorders. To address these issues, I developed an automated, high-throughput procedure to efficiently train rats to perform a task requiring context-dependent selection and accumulation of sensory evidence. Rats were trained in parallel across many rigs, allowing me to train 62 rats to solve this task with high accuracy. While rats performed the task, I recorded neural responses in frontal cortex, and I developed computational analyses to recover neural population trajectories evoked by single pulses of evidence. Using recurrent neural networks, I then showed that such pulse-evoked trajectories can be related to distinct mechanisms underlying task solution. Surprisingly, neural data was highly heterogeneous across individual animals, revealing that each rat performs the task using different combinations of mechanisms. Further validating these results, neurally inferred mechanisms were in remarkably high agreement with predicted behavioral signatures. This approach opens the door to the study of individual variability in neural computations underlying higher cognition.
Biography
Marino Pagan is a principal investigator at the Simons Initiative for the Developing Brain at the University of Edinburgh. He received his B.S. in Computer Engineering and his M.S. in Control Engineering from Scuola Superiore Sant’Anna and University of Pisa in Italy. He completed his Ph.D. in Neuroscience at University of Pennsylvania in the laboratory of Nicole Rust, where he studied the neural substrates of visual object search in macaque monkeys using electrophysiology and computational modelling. In his postdoctoral research with Carlos Brody at Princeton University, Pagan studied the neural mechanisms underlying cognitive flexibility in rats performing complex rule-switching tasks. With the support of a SFARI Bridge to Independence Fellowship, Pagan aims to investigate the neural circuits underlying flexible decision-making, and how these circuits are altered by genetic mutations implicated in neurodevelopmental disorders.