The long term objective of this proposal is to investigate the functional role of zona incerta on cortical function, plasticity and development. Previous studies have suggested that zona incerta is associated with a variety of complex functions including, pain, visual discrimination, ingestive behavior, sensory/motor control mechanisms, arousal and attention. Recently, we have demonstrated that neurons in zona incerta project directly to the whole cerebral cortex and this pathway is bilateral, roughly topographically organized and developed early in post-natal life. In addition, many of these incerto-cortical projecting neurons are GABAergic. This pathway has not been described previously and our current hypothesis is that zona incerta may be similar in functions as the monoaminergic and cholinergic systems. In the proposed studies, we will use neuroanatomical, immunohistochemical and electrophysiological approaches to investigate the physiological role of zona incerta on cortical development, plasticity and normal function. The main contribution of this proposal should provide new insights on cortical function and related diseases such as Alzheimer and Schizophrenia.