Neurosalience #S6E11 with Alessandro Gozzi - Decoding connectivity: From mouse brains to human mind

"We inhibited a brain region and connectivity went up. I thought it was an artifact..."Dr. Alessandro Gozzi is a systems neuroscientist investigating how the brain functions as an integrated network and how disruptions in that network relate to behavior and mental health. He is Senior Scientist and Group Leader of the Functional Neuroimaging Laboratory at the Italian Institute of Technology in Rovereto, Italy. His research combines fMRI, functional ultrasound imaging, optogenetics, chemogenetics, electrophysiology, and computational modeling to decode the neural underpinnings of brain connectivity in rodent models, with the goal of bridging circuit-level findings to human psychopathology.In this conversation, Dr. Gozzi unpacks what resting-state fMRI connectivity actually reflects and why the answer may be more surprising than the field assumes. Drawing on a series of elegant chemogenetic and pharmacological manipulations in mice, he reveals how regional excitability, rather than direct synaptic communication, may be a dominant driver of the connectivity patterns we observe. Within this context, the conversation explores the paradoxical relationship between neural silencing and hyperconnectivity, the evolutionary conservation of brain networks across species, and what rodent models of autism can and cannot tell us about human psychiatric disorders. Join the conversation to discover how mechanistic animal studies are reshaping our understanding of human brain connectivity.We hope you enjoy this episode!Chapters:00:00 - Introduction to Dr. Alessandro Gozzi05:12 - Gozzi’s Unconventional Journey into Neuroscience13:17 - Transitioning from Industry to Academia20:49 - The Relevance of Rodent Models in Understanding Autism32:04 - Exploring the Complexities of Brain Connectivity38:57 - Excitability and Its Role in Connectivity Patterns42:27 - Exploring fMRI Connectivity and Local Computation45:28 - The Role of the Hearst Index in Brain Activity54:00 - Implications for Treatment in Psychiatric Disorders58:42 - The Intersection of Biology and Neuroscience Research01:07:08 - Balancing Life and Science: Personal ReflectionsWorks mentioned:00:12:48 - Gutierrez-Barragan, D. et al. (2024). Evolutionarily conserved fMRI network dynamics in the mouse, macaque, and human brain. https://doi.org/10.1038/s41467-024-49245-600:17:40 - Zerbi, V., Pagani, M. et al. (2021). Brain mapping across 16 autism mouse models reveals a spectrum of functional connectivity subtypes. https://doi.org/10.1038/s41380-021-01245-400:18:00 - Pagani, M. et al. (2021). mTOR-related synaptic pathology causes autism spectrum disorder-associated functional hyperconnectivity. https://doi.org/10.1038/s41467-021-26520-800:29:50 - Pagani, M. et al. (2025). Biological subtyping of autism via cross-species fMRI. https://doi.org/10.1101/2025.03.04.64140000:40:40 - Rocchi, F. et al. (2022). Increased fMRI connectivity upon chemogenetic inhibition of the mouse prefrontal cortex. https://doi.org/10.1038/s41467-022-28591-300:43:30 - Trakoshis, S., Martínez-Cañada, P. et al. (2020). Intrinsic excitation-inhibition imbalance affects medial prefrontal cortex differently in autistic men versus women. https://doi.org/10.7554/eLife.5568400:45:10 - Newbold, D.J. et al. (2020). Plasticity and spontaneous activity pulses in disused human brain circuits. https://doi.org/10.1016/j.neuron.2020.05.007Episode producer:Xuqian Michelle Li