Many organisms rely on a capacity to rapidly replicate, disperse, and evolve when faced with uncertainty and novelty. But mammals do not evolve and replicate quickly. They rely on a sophisticated nervous system to generate predictions and select responses when confronted with these challenges. An important component of their behavioral repertoire is the adaptive context-dependent seeking or avoiding of perceptually novel objects, even when their values have not yet been learned. Here, we outline recent cross-species breakthroughs that shed light on how the zona incerta (ZI), a relatively evolutionarily conserved brain area, supports novelty-seeking and novelty-related investigations. We then conjecture how the architecture of the ZI’s anatomical connectivity – the wide-ranging top-down cortical inputs to the ZI, and its specifically strong outputs to both the brainstem action controllers and to brain areas involved in action value learning – place the ZI in a unique role at the intersection of cognitive control and learning.
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