Multidimensional imbalances in excitation/inhibition in Fragile-X Syndrome
A leading theory for multiple brain disorders, such as schizophrenia and autism, is that they arise from developmental imbalances in excitatory and inhibitory (E/I) brain circuitry. However, a simple one-dimensional see-saw version of this model cannot be true: if so, we could cure all such disorders just by giving patients drugs that increased or decreased inhibition until balance was restored. I will present our efforts to develop a multi-dimensional theory of E/I imbalance, using data from Fragile-X mouse models as an example case.
We used a combination of computational modelling and large-scale analysis of in vivo 2-photon Ca2+ imaging data from somatosensory cortex of wild-type and Fragile-X mouse models. I will report our three main findings: 1) redundancies and divergences in the effects of various E/I synaptic and cellular properties on network activity; 2) evidence for orthogonal changes in circuit properties of Fragile-X mice at different stages of development; 3) a reduction in the effective number of circuit activity patterns in young Fragile-X mice compared to wild-type, but a surprising increase in adult Fragile-X mice. These findings may open qualitatively new strategies for treating Fragile-X Syndrome and related disorders.
(Joint work with Tiago Goncalves, Carlos Portera-Cailliau, and Terry Sejnowski)
18 May 2016, 13:00 (Wednesday, 4th week, Trinity 2016)
Tinsley Building, Mansfield Road OX1 3TA
Dr Cian O'Donnell (University of Bristol)
Centre for Neural Circuits and Behaviour
Dr Tim P Vogels (University of Oxford),
Dr Rui Ponte Costa (University of Oxford)
Oxford Neurotheory Forum