Oscillatory entrainment of subthalamic nucleus neurons and behavioural consequences in rodents and primates E. C. J. Syed, 1,2, * A. Benazzouz, 1,2,3, * M. Taillade, 1,2 J. Baufreton, 1,2 K. Champeaux, 1,2,3 M. Falgairolle, 1,2 B. Bioulac, 1,2,3 C. E. Gross 1,2,3 and T. Boraud 1,2,3 1 Institut des Maladies Neurode ´ge ´ne ´ ratives, CNRS UMR 5293, Universite ´ Bordeaux Segalen, Bordeaux Cedex, France 2 Institut des Maladies Neurode ´ge ´ne ´ ratives, CNRS UMR 5293, Bordeaux Cedex, France 3 Centre Hospitalier Universitaire de Bordeaux, Bordeaux Cedex, France Keywords: beta oscillations, local field potentials, Parkinson’s disease, stimulation Abstract We investigated the functional role of oscillatory activity in the local field potential (LFP) of the subthalamic nucleus (STN) in the pathophysiology of Parkinson’s disease (PD). It has been postulated that beta (15–30 Hz) oscillatory activity in the basal ganglia induces PD motor symptoms. To assess this hypothesis, an LFP showing significant power in the beta frequency range (23 Hz) was used as a stimulus both in vitro and in vivo. We first demonstrated in rat brain slices that STN neuronal activity was driven by the LFP stimulation. We then applied beta stimulation to the STN of 16 rats and two monkeys while quantifying motor behaviour. Although stimulation-induced behavioural effects were observed, stimulation of the STN at 23 Hz induced no significant decrease in motor performance in either rodents or primates. This study is the first to show LFP-induced behaviour in both rats and primates, and highlights the complex relationship between beta power and parkinsonian symptoms. Introduction Synchronized oscillatory activity in the central nervous system has attracted a great deal of interest during the last decade, as it is thought to be important in brain functions such as sleep (Steriade, 2005), memory consolidation (Buzsaki, 2005), and sensory information processing (Neuenschwander et al., 2002), as well as some patho- physiological processes such as epilepsy (Steriade, 2005) and Parkinson’s disease (PD) (Hutchison et al., 2004; Boraud et al., 2005). These oscillations are easily detected with local field potential (LFP) or multiple electrode neuronal recordings, but the former are notoriously more sensitive than the latter (Zeitler et al., 2006). Determining whether LFP carries information or serves some com- putational role requires a description of a feasible read-out neuronal mechanism (Boraud et al., 2005) for this information. Most previous studies have tried to find correlations between quantitative or qualitative behavioural parameters and significant power in the LFP signal within particular frequency bands. PD provides a quite typical example of this classical method applied to the study of the functional role of synchronized oscillations. PD is characterized by a progressive loss of dopaminergic mesencephalic neurons resulting in the mani- festation of motor impairment, including akinesia, rigidity, tremor, and postural disabilities. These symptoms are associated with a complex disorganization of the neuronal activity occurring in the cortex–basal ganglia (BG)–thalamo-cortical motor circuits (DeLong, 1990; Albin et al., 1995). The activity of BG neurons, especially that of the subthalamic nucleus (STN), becomes synchronized and oscillatory in the 15–30-Hz range (beta band) and in the 3–10-Hz range (theta–alpha band) in PD patients (Levy et al., 2000, 2002; Ku ¨hn et al., 2005; Weinberger et al., 2006). Beta band oscillations have been observed in rat models of PD, and theta–alpha band oscillations have been recorded in monkey models of PD (Bergman et al., 1998; Hutchison et al., 2004). Oscillatory activities in LFP recordings in the same beta and theta bands have also been identified in PD patients (Brown & Marsden, 1999; Boraud et al., 2005). LFP activity in the beta range in the cortex and STN of PD patients has been correlated with motor impairment, in particular bradykinesia (Ray et al., 2008; Kuhn et al., 2009; Pogosyan et al., 2009; Chen et al.). From these studies, a direct causal link between the oscillatory pattern of BG neurons and the manifestation of PD motor symptoms has been proposed (Brown, 2003b). Indeed, a number of studies in which the STN was stimulated with low-frequency pulses have shown a correlation between stimu- lation and bradykinesia and rigidity (Timmermann et al., 2004; Fogelson et al., 2005a; Chen et al., 2007; Eusebio et al., 2008). Such a causal link has, however, been questioned by other theoretical (Leblois et al., 2006) and experimental (Leblois et al., 2007; Degos et al., 2009) approaches. In this study, we used an LFP signal showing significant power in the beta band as a stimulus in order to mimic pathophysiological conditions more closely. This particular stimula- tion will be referred to as BETA-STIM in the rest of the article. Correspondences: Thomas Boraud, 1 Institut des Maladies Neurode ´ge ´ne ´ratives, as above. E-mail: tboraud@u-bordeaux2.fr Abdelhamid Benazzouz, 1 Institut des Maladies Neurode ´ge ´ne ´ratives, as above. E-mail: abdelhamid.benazzouz@u-bordeaux2.fr *E.S and A.B. contributed equally to this work. Received 3 February 2012, revised 3 July 2012, accepted 5 July 2012 European Journal of Neuroscience, pp. 1–12, 2012 doi:10.1111/j.1460-9568.2012.08246.x ª 2012 The Authors. 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