Changes in the firing pattern of globus pallidus neurons after the degeneration of nigrostriatal pathway are mediated by the subthalamic nucleus in the rat

Abstract

Changes in the neuronal activity of globus pallidus (GP) have been shown in animal models of parkinsonism. In order to study the implication of the subthalamic nucleus (STN) in these changes, the effects of STN lesions alone or in combination with 6-hydroxydopamine (6-OHDA) -induced damage to the substantia nigra compacta (SNc) were examined in rats using electrophysiological recordings of GP cells. In normal rats, the firing rate was 22.1+/-1.4 spikes/s. The pattern was regular in 45%, irregular in 49% and bursty in 6% of the cases. In rats with STN lesions, the firing rate of GP units (20.15+/-1.25 spikes/s) did not differ from that of normal rats and only regular (46%) and irregular (54%) cells were found; a bursty pattern was not observed. 6-OHDA lesions of the SNc induced no change in the firing rate of GP neurons (21.5+/-1.4 spikes/s, P>0.05) but a significant decrease in the percentage of regular cells (27%, P<0.001), a significant increase in burst cells (21%, P<0.001) with no change in the percentage of irregular units (52%) were observed. In rats with combined SNc and STN lesions, the firing pattern did not change from that of normal rats. The present results show that STN lesions induced the disappearance of bursts in normal rats and normalization of firing pattern in the GP units of rats with 6-OHDA lesions suggesting that the STN plays an important role in the modulation of the pattern of activity of GP neurons which may account for the therapeutic effect of STN lesions in Parkinson's disease.

Dissociable effects of dopamine on neuronal firing rate and synchrony in the dorsal striatum

“…Dopamine (DA) transmission within the basal ganglia is essential for the normal expression of spontaneous and voluntary movement (Poirier et al, 1975; Amalric and Koob, 1987; Fletcher and Starr, 1987; Zhou and Palmiter, 1995). Dysfunction of DA transmission has profound consequences upon the function of the basal ganglia, altering downstream activity and motor output (Lloyd, 1977; Filion, 1979; Sanderson et al, 1986; Pan and Walters, 1988; MacLeod et al, 1990; Calabresi et al, 1993; Burbaud et al, 1995; Chesselet and Delfs, 1996; Levy et al, 1997; Murer et al, 1997; Rohlfs et al, 1997; Moore et al, 1998; Ni et al, 2000; Chen et al, 2001; Magill et al, 2001; West and Grace, 2002). Loss of DA projections is the characteristic morphological feature of Parkinson's disease (PD) (Shimohama et al, 2003), wherein degeneration of substantia nigra pars compacta (SNc) projections results in decreased extracellular striatal DA levels (Schober, 2004).…”

Neuroinformatics and modeling of the basal ganglia: bridging pharmacology and physiology

“…Changes in the firing pattern from regular to bursting activity in the STN are also seen in the 6-OHDA rat [16]. In this rat model of PD, STN lesions reduce the appearance of bursting activity in globus pallidus [17]. Ideally, a model of STN neurons should not only be able to exhibit bursting and nonbursting modes, but also inform which channel types may be key in the transition to, or disposition for, bursting activity.…”

Modulation of in vivo GABA-evoked responses by nitric oxide-active compounds in the globus pallidus of rat

“…Under our experimental conditions, all the examined neurons were characterized by spontaneous activity with biphasic negative/positive extracellular waveforms. On the basis of discharge features, we distinguished the recorded neurons between regularly and irregularly discharging units, all probably representing projection neurons (Cooper and Stanford 2000;Nambu and Llinas 1997;Ni et al 2000;Sardo et al 2002a). Our analyses ruled out any discharge-related responses to pharmacological treatment; moreover, the application of drugs did not modify the discharge patterns of tested neurons.…”