Molecular and Cellular basis of cognitive flexibility in Autism Spectrum Disorder models

Beatriz Rico (primary)
Developmental Neurobiology
King's College London
Adil Khan (secondary)
Developmental Neurobiology
King's College London

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.


BBSRC Area
Genes, development and STEM* approaches to biology
Area of Biology
DevelopmentNeurobiology
Techniques & Approaches
GeneticsImage ProcessingMathematics / StatisticsMicroscopy / ElectrophysiologyMolecular BiologySimulation / Modelling