Marcos Sintes. Mesoscopic monitoring and analysis of cortical excitation/ inhibition balance in an animal model of synaptic dysfunction


Departing from the traditional molecular-mechanistic view point, several neuropsychiatric spectrum disorders are more recently conceptualized as diseases of neuronal circuit dynamics. Under this concept, the balance of excitation and inhibition (E/I balance) as well as a balance of local versus long-range connections are critical for normal brain functioning, and are altered in neuropsychiatric disorders like autism spectrum disorders (ASD). Early detection of aberrant circuit developments and preventive pharmacological interventions would meet a medical need of outstanding importance.

Research Challenge

To test the above hypothesis, we will employ state of the art mesoscopic voltage imaging techniques in mouse models of ASD to monitor and determine how the cortical E/I balance and connectivity is affected at the neuronal circuit level, both at awake resting state and during processing of sensory information. We will then test how this circuit dynamics is influenced by neuromodulatory effects mediated via 5HT receptors.

The laboratory of Professor Thomas Knöpfel at the Imperial College London has extensive expertise in the development and application of genetically encoded voltage indicators that will be instrumental for performing the circuit-centric analysis in a cell type-specific manner. Our conceptual framework motivates the development of circuit-centric diagnostic markers as well as novel therapeutic approaches.

Supervision and Secondments

The PhD project will be carried out in Thomas Knöpfel’s laboratory at the Imperial College London (ICL). The ESR will enrol in the Centre for Doctoral Training (CTD) Programme at Imperial. The project also features (extended stays) at IBPS-CNRS (Catalina Betancur) and the CHUC (Guiomar Oliveira).

Supervisor: Thomas Knöpfel (

Host Location: Centre for Neurotechnology, Imperial College London, London, United Kigdom.

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