Abstract
Cortical network activity is generated by complex interactions between excitatory pyramidal cells and inhibitory interneurons. A highly influential hypothesis of autism predicts that overexcitation in specific cortical circuits might disrupt information processing and lead to abnormal patterns of activity and seizures in a subset of individuals with autism spectrum disorders (ASD). Defective maturation of inhibitory circuits has been proposed as an underlying cause for epilepsy- autism comorbidity. This project will explore the contribution of interneurons to the function of cortical circuitry in mouse models of ASD, with a focus in cognitive flexibility, a process severely affected in ASD patients.
References
1 Favuzzi E*, Deogracias R*, Marques-Smith A, Maeso P, Exposito-Alonso D, Kroon T., Baglia M., Fernandez- Maraver E, Rico B. Distinct molecular programs regulate synapse specificity in cortical inhibitory circuits, Science, 263:413 (2019)
2 Favuzzi I & Rico B (2018). Molecular diversity underlying cortical excitatory and inhibitory synapse development. Current Opinion in Neurobiology, 53:8-15.
3 Favuzzi I, Marques-Smith A, Deogracias R, Winterflood CM, Mantoan L, Fernandes C, Ewers H & Rico B (2017). Activiy-dependent gating of Parvalbumin interneuron function by perineuronal nets, Neuron 95: 639-655.
4 Del Pino I, Garcia-Frigola C, Dehorter N, Brotons-Mas JR, Alvarez-Salvado E, Martinez De Lagran M, Ciceri G, Gabaldon MV, Moratal D, Dierssen M, Canals S, Marín O*, Rico B* (2013) Erbb4 deletion from fast-spiking interneurons causes schizophrenia-like phenotypes. Neuron 79:1152-1168.
5 Del Pino I, Rico B*, Marín O* (2018). Neural circuit dysfunction in mouse models of neurodevelopmental disorders, Current Opinion in Neurobiology, 48:174-182.