Dopamine deficiency increases synchronized activity in the rat subthalamic nucleus

• Published in: Brain research 2012-01, Vol.1434 (24), p.142-151
• Main Authors: Lintas, Alessandra, Silkis, Isabella G, Albéri, Lavinia, Villa, Alessandro E.P
• Format: Article
• Language: English
• Subjects: 6-OHDA-lesioned rat; Action Potentials; Action Potentials - genetics; Animals; apomorphine; Basal ganglia; brain; Dopamine; Dopamine - deficiency; drugs; Firing pattern; ganglia; Humans; Life Sciences; Male; Neurobiology; Neurology; Neurons; Neurons - pathology; Neurons and Cognition; Parkinson Disease; Parkinson Disease - genetics; Parkinson Disease - metabolism; Parkinson's disease; pathophysiology; patients; Rats; Rats, Wistar; sorting; Subthalamic Nucleus; Subthalamic Nucleus - metabolism; Subthalamic Nucleus - pathology; Up-Regulation; Up-Regulation - genetics
• ISSN: 0006-8993; 1872-6240; 0006-8993
• DOI: 10.1016/j.brainres.2011.09.005

Abstract Abnormal neuronal activity in the subthalamic nucleus (STN) plays a crucial role in the pathophysiology of Parkinson's disease (PD). In this study we investigated changes in rat STN neuronal activity after 28 days following the injection of 6-OHDA in the substantia nigra pars compacta (SNc). This drug provoked a lesion of SNc that induced a dopamine (DA) depletion assessed by changes in rotating capacity in response to apomorphine injection and by histological analysis. By means of extracellular recordings and waveshape spike sorting it was possible to analyze simultaneous spike trains and compute the crosscorrelations. Based on the analysis of the autocorrelograms we classified four types of firing patterns: regular (Poissonian-like), oscillatory (in the range 4–12 Hz), bursty and cells characterized by a long refractoriness. The distribution of unit types in the control (n = 61) and lesioned (n = 83) groups was similar, as well as the firing rate. In 6-OHDA treated rats we observed a significant increase (from 26% to 48%) in the number of pairs with synchronous firing. These data suggest that the synchronous activity of STN cells, provoked by loss of DA cells in SNc, is likely to be among the most significant dysfunctions in the basal ganglia of Parkinsonian patients. We raise the hypothesis that in normal conditions, DA maintains a balance between funneling information via the hyperdirect cortico-subthalamic pathway and parallel processing through the parallel cortico-basal ganglia-subthalamic pathways, both of which are necessary for selected motor behaviors. This article is part of a Special Issue entitled ‘Neural Coding’.