Carlos Portera-Cailliau's laboratory is applying a symptom-to-circuit approach to understanding neurodevelopmental disorders, with a focus on autism. 1. How are cortical circuits assembled during typical brain development? 2. What are the underlying circuit defects in autism and intellectual disability? 3. What are the best ways to model neuropsychiatric symptoms? His laboratory is trying to answer these questions using the latest state of the art tools in neuroscience research, such as in vivo 2-photon calcium imaging and silicon probes to record network activity, chemogenetics with DREADDs or optogenetics to manipulate neuronal activity, and sophisticated behavioral tasks.
Their research is particularly relevant to neuropsychiatric disorders that lack distinct neuropathological features and are therefore more likely caused by subtle alterations in how neuronal activity propagates across brain circuits. The traditional approach to understand how symptoms arise in complex neuro-psychiatric disorders has been to start at the molecular level and use gain- or loss-of-function manipulations of a given pathway to correct synaptic defects and/or abnormal mouse behavior. Unfortunately, this approach has often overlooked potential circuit alterations that could link the molecular/synaptic defects with the behavioral phenotype, which may explain why so far it has had limited translational potential. Instead, Dr. Portera-Cailliau's team has adopted a symptom-to-circuit approach to reverse engineer how different symptoms in neurodevelopmental disorders arise from specific network level disruptions in neuronal connectivity and function.
Chari T, A Hernandez, and C Portera-Cailliau (2023) “A novel head-fixed assay for social touch in mice uncovers aversive responses in two autism models.” J Neuroscience, Oct 25;43(43):7158-7174.
Kourdougli N*, A Suresh, B Liu, P Juarez, A Lin, DT Chung, A Graven Sams, M Gandal, V Martínez-Cerdeño, D Buonomano, B Hall, C Mombereau, and C Portera-Cailliau (2023) “Improvement of sensory deficits in Fragile X mice by boosting cortical interneuron activity after the critical period.” Neuron. Sep 20;111(18):2863-2880
Contractor A, I Ethell, and C Portera-Cailliau (2021) Cortical interneurons in autism. Nature Neurosci, Dec;24(12):1648-1659
Goel A, D Cantu, J Guilfoyle, GR Chaudhari, A Newadkar, B Todisco, D De Alba, N Kourdougli, LM Schmitt, E Pedapati, CA Erickson, and C Portera-Cailliau. Impaired perceptual learning in a mouse model of Fragile X syndrome is mediated by parvalbumin neuron dysfunction in V1 and is reversible. Nature Neuroscience. Oct;21(10):1404-1411.
He CX, Cantu DA, Mantri SS, Zeiger WA, Goel A, Portera-Cailliau C (2017) Tactile defensiveness and impaired neuronal adaptation in the Fmr1 knock-out mouse model of autism. J Neurosci, 37:6475-6487
O’Donnell C, JT Gonçalves, C Portera-Cailliau, and TJ Sejnowski (2017) Beyond excitation/inhibition imbalance in multidimensional models of neural circuit changes in brain disorders. eLife Oct 11;6. pii: e26724
Contractor A, VA Klyachko, and C Portera-Cailliau (2015). Altered neuronal and circuit excitability in Fragile X syndrome. Neuron, 87:699-715
Gonçalves JT, Anstey J, Golshani P, Portera-Cailliau C (2013). Circuit level defects in the developing neocortex of fragile X mice. Nature Neurosci, 16:903-9