Controlling Neuronal Activity with Light: from Brain Waves to Single Synapses

The large number of photoswitchable biomolecules discovered and developed in recent years covers a great variety of cellular functions like catalysis of metabolic processes, cytoskeletal polymerization and motors, nucleic acids dynamics, intracellular signaling and perhaps most dazzlingly membrane excitability, which has been at the focus of photopharmacology and optogenetics to study neurobiology. The dream of precisely and remotely photocontrolling every aspect of neuronal activity in intact tissue appears within reach and offers the promise of understanding the underlying molecular mechanisms. Recent and ongoing projects at IBEC focused on photopharmacology will be reviewed, including the development and applications of photoswitchable ligands of ion channels and receptors to control neuronal excitation and inhibition with light. These molecular tools allow spatiotemporal control of endogenous proteins in vivo and at multiple scales, from emerging cortical waves in the brain to individual synapses.