Excitatory synapses in the brain form on structures called “spines,” which are essential for learning, memory, and are main targets of psychiatric medication. We use genetic labeling and chemical manipulation of these spines to study brain functions related to perception, emotion, and decision-making. This approach, based on the molecular makeup of synapses, allows us to explore brain function in whole organisms, including mice and primates like marmosets. This method could lead to new strategies for identifying molecules and techniques that may inform future therapies.