Optimisation of photostimulation targeting muscarinic receptors

Behavior is driven by specific neuronal activity and can be directly associated with characteristic brain states. The oscillatory activity of neurons contains information about the mental state of an individual, and the transition between physiological brain states is largely controlled by neuromodulators. Manipulating neural activity, brain rhythms or synchronization is of significant therapeutic interest in several neurological disorders and can be achieved by different means such as transcranial current and magnetic stimulation techniques, and by light through optogenetics, although the clinical translation of the latter is hampered by the need of gene therapy. Here, we directly modulate brain rhythms with light using a novel photo-switchable muscarinic agonist. Synchronous slow wave activity is transformed into a higher frequency pattern in the cerebral cortex in in vitro ferret slices in vitro. These results open the way to the study of the neuromodulation and control of spatiotemporal patterns of activity and pharmacology of brain states, their transitions, and their links to cognition and behavior, in different organisms without requiring any genetic manipulation (Barbero-Castillo 2020).