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Molecular and Cellular Basis of Cognitive Flexibility in Autism Spectrum Disorder Models

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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.

Disciplines and Techniques
Project supervisor/s
Professor Beatriz Rico
Beatriz is interested in understanding how genes are involved in the development of neuronal circuits and the consequences on their disruption.
King's College London
Dr. Adil Khan
Adil's reearch focuses on cognition in mice by combining chronic in-vivo two photon calcium imaging of multiple cell classes, targeted optogenetic manipulations, viral vector based functional circuit mapping, and quantitative mouse behavioural assays.
King's College University
Distinct molecular programs regulate synapse specificity in cortical inhibitory circuits
Favuzzi E*, Deogracias R*, Marques-Smith A, Maeso P, Exposito-Alonso D, Kroon T., Baglia M., Fernandez- Maraver E, Rico B.
Science, 263:413
Molecular diversity underlying cortical excitatory and inhibitory synapse development
Favuzzi I & Rico B
Current Opinion in Neurobiology, 53:8-15
Activiy-dependent gating of Parvalbumin interneuron function by perineuronal nets
Favuzzi I, Marques-Smith A, Deogracias R, Winterflood CM, Mantoan L, Fernandes C, Ewers H & Rico B
Neuron 95: 639-655.
Erbb4 deletion from fast-spiking interneurons causes schizophrenia-like phenotypes
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*
Neuron 79:1152-1168
Neural circuit dysfunction in mouse models of neurodevelopmental disorders
Del Pino I, Rico B*, Marín O*
Current Opinion in Neurobiology, 48:174-182