Models of the subthalamic nucleus: The importance of intranuclear connectivity

A coherent set of models is presented that provide novel and testable predictions about the functional role of the subthalamic nucleus (STN) in the basal ganglia. The STN is emerging as an important target for novel therapeutic strategies for the alleviation of Parkinsonian type symptoms [Lancet 345 (1995) 91; Science 249 (1990) 1436]. Computational and mathematical models based on the properties of the STN and its interactions are reviewed. These models focus on core anatomical and physiological data that span many levels. By assessing models of anatomy, dynamic network models, and a detailed model of a recent pharmacological experiment, we can expose the primary modes of STN function and highlight their underlying properties. We show that the presence of functional interactions between STN projection neurons is critical in defining its behaviour and how it interacts with other basal ganglia nuclei. Pulses or switch-like activity patterns emerge in the models as a consequence of these local interactions. Furthermore, the models demonstrate that this behaviour can break down under abnormal conditions resulting in low frequency bursting oscillations. Such oscillations may play a role in symptoms of Parkinson’s disease.