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Cdr1as/ciRS-7 is a circular RNA conserved in mammals and highly expressed in brain. It features a large number of microRNA target sites bound in vivo by miR-7/miR-671. Cdr1as regulates synaptic activity under stress in a temporal, spatial, and neuron-specific manner. We review genetic, molecular, evolutionary, and physiological data to discuss how Cdr1as and its interactors form a functionally important network of non-coding RNAs that regulates neuronal adaptability. We provide a framework to explore potential roles of other non-coding RNA networks on brain function and their diagnostic and therapeutic potential.