NEUROSCIENCE FOREFRONT REVIEW ACTIVE DECORRELATION IN THE BASAL GANGLIA

The cytoarchitecturally-homogeneous appearance of the globus pallidus, subthalamic nucleus and substantia nigra has long been said to imply a high degree of afferent convergence and sharing of inputs by nearby neurons. Moreover, axon collaterals of neurons in the external segment of the globus pallidus and the substantia nigra pars reticulata arborize locally and make inhibitory synapses on other cells of the same type. These features suggest that the connectivity of the basal ganglia may impose spike-time correlations among the cells, and it has been puzzling that experimental studies have failed to demonstrate such correlations. One possible solution arises from studies of firing patterns in basal ganglia cells, which reveal that they are nearly all pacemaker cells. Their high rate of firing does not depend on synaptic excitation, but they fire irregularly because a dense barrage of synaptic inputs normally perturbs the timing of their autonomous activity. Theoretical and computational studies show that the responses of repetitively-firing neurons to shared input or mutual synaptic coupling often defy classical intuitions about temporal synaptic integration. The patterns of spike-timing among such neurons depend on the ionic mechanism of pacemaking, the level of background uncorrelated cellular and synaptic noise, and the firing rates of the neurons, as well as the properties of their synaptic connections. Application of these concepts to the basal ganglia circuitry suggests that the connectivity and physiology of these nuclei may be configured to prevent the establishment of permanent spike-timing relationships between neurons. The development of highly synchronous oscillatory patterns of activity in Parkinson's disease may result from the loss of pacemaking by some basal ganglia neurons, and accompanying breakdown of the mechanisms responsible for active decorrelation. (c) 2013 IBRO. Published by Elsevier Ltd. All rights reserved.