Beyond excitation/inhibition imbalance in multidimensional models of neural circuit changes in brain disorders.
A leading theory holds that neurodevelopmental brain disorders arise from imbalances in excitatory and inhibitory (E/I) brain circuitry. However, it is unclear whether this one-dimensional model is rich enough to capture the multiple neural circuit alterations underlying brain disorders. Here, we combined computational simulations with analysis of in vivo two-photon Ca2+ imaging data from somatosensory cortex of Fmr1 knock-out (KO) mice, a model of Fragile-X Syndrome, to test the E/I imbalance theory. We found that: (1) The E/I imbalance model cannot account for joint alterations in the observed neural firing rates and correlations; (2) Neural circuit function is vastly more sensitive to changes in some cellular components over others; (3) The direction of circuit alterations in Fmr1 KO mice changes across development. These findings suggest that the basic E/I imbalance model should be updated to higher dimensional models that can better capture the multidimensional computational functions of neural circuits.
Department of Computer Science, University of Bristol, Bristol, United Kingdom. Howard Hughes Medical Institute, Salk Institute for Biological Studies, La Jolla, United States. Dominick Purpura Department of Neuroscience, Albert Einstein College of Medicine, Bronx, United States. Department of Neurology, David Geffen School of Medicine at UCLA, Los Angeles, United States. Department of Neurology, David Geffen School of Medicine at UCLA, Los Angeles, United States. Department of Neurobiology, David Geffen School of Medicine at UCLA, Los Angeles, United States. Howard Hughes Medical Institute, Salk Institute for Biological Studies, La Jolla, United States. Division of Biological Sciences, University of California at San Diego, La Jolla, United States.
