الفهرس 
Introduction and Literature ReviewOnly 14 pages are availabe for public view
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Abstract
Classical models of basal ganglia (BG) function and dysfunction postulate that BG circuits encode and conduct motor behaviors through a series of changes in BG neuronal firing rate, with little emphasis on the firing pattern (i.e. synchrony level and oscillatory activity). However, it has been reported that synchronized neuronal oscillations play essential role for optimal communication within and between dispersed neuronal networks, and thus for a healthy motor system. Consequently, dysregulation of these neuronal firing patterns could be pathological. Indeed, in Parkinson’s disease (PD) and its animal models, there is a host of evidence showing that throughout BG networks, neurons burst and oscillate ‘excessively’ in the parkinsonian brain, in particular, at beta frequency (15-30 Hz) which might be responsible for akinesia. The neuronal substrate underlying the emergence and propagation of these exaggerated beta oscillations is still unknown, but the external globus pallidus (GPe) has been proposed to be of particular importance. Furthermore, the conventional ideas about the role GPe plays in BG networks have changed drastically over the past two decades: from being a simple relay station in the indirect pathway of BG to a central nucleus controlling the firing rate and pattern of the entire BG circuits. However, the causal implication of GPe on its target BG nuclei has never been tested directly in vivo. That being mentioned, here we hypothesize that GPe could control not only the firing rate, but also the firing pattern of target BG nuclei. To test the latter, we specifically probed whether GPe is sufficient to generate and further propagate abnormal beta oscillations in downstream BG and cortical circuits. This constitutes a major goal for understanding BG functions in health and disease and will provide new mechanistic insights into those pathological oscillations in PD patients and how they might be better controlled for symptomatic benefit. To assess this hypothesis, we combined cutting edge optogenetic toolboxes in normal rats to manipulate the inputs coming from GPe with electrophysiological recordings in its target nuclei; the subthalamic nucleus (STN) and the substantia nigra pars reticulata (SNR) to test the manipulation effect at different functional levels. Our results support the view that GPe neurons play a key role in controlling the firing rate of target BG nuclei and can powerfully drive and orchestrate beta oscillations in BG networks in vivo.