Editor's Note: These short reviews of a recent paper in the Journal, written exclusively by graduate students or postdoctoral fellows, are intended to mimic the journal clubs that exist in your own departments or institutions. For more information on the format and purpose of the Journal Club, please see http://www.jneurosci.org/misc/ifa_features.shtml.
Emergent Basal Ganglia Pathology within Computational Models
Bradley VoytekHelen Wills Neuroscience Institute, University of California, Berkeley, California 94720-3190Review of Leblois et al. (http://www.jneurosci.org/cgi/content/full/26/13/3567) Advances in neurobiology and increased computational capabilities have paved the way for more realistic neuronal network models. For a model to be complete, it must account for known neuroanatomy, network electrophysiology, pharmacology, pathophysiology, and behavioral findings. Although the vast interconnectedness of the brain makes the formulation of a complete model computationally restrictive, scaled models of anatomical subsystems have offered new insights into brain function.One particularly attractive system to model is the basal ganglia. The anatomy and electrophysiology of this system of subcortical, prosencephalic nuclei has been well described and is thus ideal for modeling. The basal ganglia consist of four main subnuclei: striatum, globus pallidus [internal segment (GPi) and external segment (GPe)], subthalamic nucleus (STN), and substantia nigra [compact (SNc) and reticular (SNr)]. Movement disorders such as Parkinson's disease (PD) have been traced to basal ganglia dysfunction. Consequently, the basal ganglia are traditionally classified as part of the extrapyramidal motor system.Parkinson's disease is characterized by the loss of dopaminergic innervation of the striatum from the SNc. Early conceptual models (DeLong, 1990) diagrammed a "direct" and "indirect" circuit within the basal ganglia. These parallel circuits diverge according to their nigrostriatal targets; the direct pathway is said to preferentially target striatal D 1 receptors, whereas the indirect pathway is said to preferentially target D 2 receptors. These receptors modulate excitation and inhibition in the circuit, respectively. Ultimately, both pathways project to the cortex via the anterior thalamus (Fig. 1).This simple model proved very useful in describing the motor effects of PD and helped guide treatment. However, recent experimental findings suggest that this model is incomplete. New PD treatments such as deep brain stimulation are difficult to reconcile within the classical model. Similarly, this model inadequately describes the role of the basal ganglia in learning, memory, language, and reward. Finally, there is mounting evidence that the D 1 /D 2 , direct/indirect segregation required by this model does not accurately describe the biology of the system. Indeed, as new experimental data are acquired, adjustments must be made to the conceptual and computational basal ganglia models. For example, Soares et al. (2004) showed that MP...