Disentangling the identity of the zona incerta: a review of the known connections and latest implications

The zona incerta (ZI) is a subthalamic region composed by loosely packed neurochemically mixed neurons, juxtaposed to the main ascending and descending bundles. The extreme neurochemical diversity that characterizes this area, together with the diffuseness of its connections with the entire neuraxis and its hard-to-reach positioning in the brain caused the ZI to keep its halo of mystery for over a century. However, in the last decades, a rich albeit fragmentary body of knowledge regarding both the incertal anatomical connections and functional implications has been built mostly based on rodent studies and its lack of cohesion makes difficult to depict an integrated, exhaustive picture regarding the ZI and its roles. This review aims to provide a unified resource that summarizes the current knowledge regarding the anatomical profile of interactions of the ZI in rodents and non-human primates and the functional significance of its connections, highlighting the aspects still unbeknown to research.