The brain presents different states depending on the communication between billions of neurons, and this network is the basis of all our perceptions, memories, and behaviours. It is often considered a “black box”, with difficult access for clinicians and researchers, as few tools are available to measure and manipulate brain neuronal networks with spatiotemporal accuracy. Now, a collaboration between the laboratories of Sanchez-Vives (IDIBAPS) and Gorostiza (IBEC) has allowed for the first time to control brain states using a molecule responsive to light, a method called photopharmacology. Results show that the compound PAI (for Phthalimide-Azobenzene-Iperoxo) developed at IBEC can specifically and locally activate muscarinic cholinergic receptors present in the cerebral cortex. They are a specific type of protein that binds acetylcholine, a neuromodulator involved in processes like learning, attention, and memory.
Transitions between brain states, such as going from being asleep to awake, recovering from anaesthesia, or waking up from a coma, are based on the transmission of chemical and electrical signals between groups of neurons that are activated synchronously, as in waves. Their oscillatory activity is often described as “brain waves” and is an emerging property of the brain cortex. When applying PAI to the intact brain, white light allowed modulating the spontaneous emerging slow oscillations in neuronal circuits and reversibly manipulating the oscillatory frequency. Thus, this molecular tool enables inducing and investigating in a controlled and non-invasive way, the transitions of brain from sleep- to awake-like states using light.
These results are a breakthrough for neuromodulation technologies to manipulate brain activity patterns, to understand their connections to cognition and behaviour, and could also lead to novel treatments for brain lesions and diseases. Since the method works in intact brain tissue and does not require genetic manipulation, these results open the door to non invasive spatiotemporal control of drug action in the human brain.
