Some certainty for the “zone of uncertainty”? Exploring the function of the zona incerta

The zona incerta (ZI), first described over a century ago by Auguste Forel as a "region of which nothing certain can be said," forms a collection of cells that derives from the diencephalon. To this day, we are still not certain of the precise function of this "zone of uncertainty" although many have been proposed, from controlling visceral activity to shifting attention and from influencing arousal to maintaining posture and locomotion. In this review, I shall outline the recent advances in the understanding of the structure, connectivity and functions of the ZI. I will then focus on a possible and often neglected global role for the ZI, one that links its diverse functions together. In particular, I aim to highlight the idea that the ZI forms a primal center of the diencephalon for generating direct responses (visceral, arousal, attention and/or posture-locomotion) to a given sensory (somatic and/or visceral) stimulus. With this global role in mind, I will then address recent results indicating that abnormal ZI activity manifests in clinical symptoms of Parkinson disease.