Alexandre Mourot (IBPS, Sorbonne University) has been awarded a prestigious program grant by the Human Frontier Science Program (HFSP together with his collaborator Graham Ellis-Davies (Mount Sinai School of Medicine, USA). This project is one of the 20 Program Grants that were awarded this year from a total of 702 letters of intent. The goal of this project is to manipulate neurotransmitter receptors of the mouse brain using cell-type specific and photocontrollable drugs, activated with near-infrared light, within the behaving mouse.

The HFSP project combines labs with expertise in synthetic chemistry and photochemistry (Ellis-Davies) and behavioral neuropharmacology (Mourot) in order to develop technologies to gain optical control over dopamine neuromodulation in the freely-moving mouse, for studies of neural circuits and behaviors.

The team proposes to use lanthanide-doped upconverting nanoparticles, chromophores which have the unique and fascinating photophysical properties that convert tissue-penetrating near-infrared light to visible light. These nanoparticles will be functionalized with caged/photoswitchable ligands for glutamate and dopamine receptors, enabling non-invasive control of the very receptors of the brain in behaving mice.

The team will further combine near-infrared photocontrol with chemo-genetic strategies to achieve optical control of receptors in defined neuronal targets. Leveraging upconverting nanoparticles in this way will provide a platform for the interrogation of dopamine-related neuropsychiatric disorders in groups of animals in naturalistic environments.