Marino Pagan

Personal profile

• 2023-present: Principal Investigator, CDBS and SIDB, University of Edinburgh
• 2015-2023: Postdoctoral researcher, Princeton University
• 2009-2014: Ph.D. in Neuroscience, University of Pennsylvania
• 2006-2009: M.S. in Control Engineering, University of Pisa
• 2003-2009: B.S. in Computer Engineering, University of Pisa

Research Theme

Synapses, Circuits and Behaviour 

Research

Our interactions with the world are highly flexible. For example, our response to the sound of our phone ringing is very different if we are at the theatre watching a play, or if we are anxiously waiting for an important call. More generally, our thoughts and actions depend heavily on the current context, which includes our goals, past experience, and future expectations. How does our brain integrate such contextual information with the constant stream of sensory stimuli to flexibly guide our decisions?

In our laboratory, we address this question using a combination of computational, behavioral, electrophysiological, and optogenetic techniques. By investigating the neural mechanisms underlying cognitive flexibility and decision-making, we aim to understand how these fundamental cognitive processes are disrupted in neuropsychiatric and neurodevelopmental disorders.

Our goal is to address three fundamental questions:

1 - What neural mechanisms underlie our ability to flexibly form decisions?

To study the neural basis of flexible decision-making, we train rats to perform sophisticated tasks with rapidly changing rules. To solve these tasks, rats learn to use contextual information to flexibly form decisions about sensory stimuli. We then study neural responses during this behavior, and we build computational models to understand the underlying mechanisms.

2 - How do neural computations underlying cognitive behavior vary across individuals?

Our recent work (Pagan et al., 2024) indicates that individual rats can use different neural mechanisms to perform an identical cognitive task. These findings highlight the importance of measuring and characterizing neural circuits at the level of individual animals. To achieve this goal, we leverage a system for automated, high-throughput behavioral training, integrated with wireless electrophysiology and optogenetics. These techniques allow us to study the learning trajectory of each individual animal, and to explore the neural substrates of individual variability.

3 - How do genetic mutations impact neural circuits underlying flexible decision-making?

Deficits in cognitive flexibility and decision-making are a profoundly debilitating feature of many neurodevelopmental disorders. Despite significant recent progress in identifying the genetic causes of these disorders, the mechanisms linking genetic mutations to cognitive deficits are still largely unknown. To address this problem, we study how flexible decision-making is altered in rat models of neurodevelopmental disorders. Using electrophysiology, optogenetics and computational analyses, we study how cellular and circuit alterations induced by genetic mutations affect cognitive computations at the system level.

Funding

Simons Initiative for the Developing Brain (SIDB)

SFARI Bridge to Independence Fellowship

Team members

• Nuria Garcia-Font (Reasearch Fellow)
• Elise Chang (PhD student)

Collaborations

Prof. Peter C Kind, University of Edinburgh, UK

Associate Prof. Oliver Hardt, Dept of Psychology, McGill/CDBS

Prof. Richard Morris, University of Edinburgh, UK

Dr. Angus Chadwick, University of Edinburgh, UK

Relevant publications

Pagan, M., Urban, L.S., Wohl, M.P., Rust, N.C. (2013). Signals in inferotemporal and perirhinal cortex suggest an untangling of visual target information. Nature Neuroscience. 16 (8), 1132-1139 https://doi.org/10.1038/nn.3433

Duan, C.A.*, Pagan, M.*, Piet, A.T.*, Kopec, C.D., Akrami, A., Riordan, A.J., Erlich, J.C., Brody, C.D. (2021) Collicular circuits for flexible sensorimotor routing, Nature Neuroscience. 24 (8), 1110-1120 https://doi.org/10.1038/s41593-021-00865-x

Pagan, M., Tang, V., Aoi, M.C., Pillow, J.W., Mante, V., Sussillo, D., Brody, C.D. (2024) Individual variability of neural computations underlying flexible decisions, Nature. https://doi.org/10.1038/s41586-024-08433-6 

Information for students:

Willingness to discuss research projects with undergraduate and postgraduate students: YES - please click here