Abstract
Electrical stimulation in the globus pallidus (GP) leads to complex modulations of neuronal activity in the stimulated nucleus. Multiple in vivo studies have demonstrated the modulation of both firing rates and patterns during and immediately following the GP stimulation. Previous in vitro studies, together with computational studies, have suggested the involvement of short-term synaptic plasticity (STP) during the stimulation. The aim of the current study was to explore in vitro the effects of STP on neuronal activity of GP neurons during local repetitive stimulation. We recorded synaptic potentials and assessed the modulations of spontaneous firing in a postsynaptic neuron in acute brain slices via a whole-cell pipette. Low-frequency repetitive stimulation locked the firing of the neuron to the stimulus. However, high-frequency repetitive stimulation in the GP generated a biphasic modulation of the firing frequency consisting of inhibitory and excitatory phases. Using blockers of synaptic transmission, we show that GABAergic synapses mediated the inhibitory and glutamatergic synapses the excitatory part of the response. Furthermore, we report that at high stimulation frequencies both types of synapses undergo short-term depression leading to a time dependent modulation of the neuronal firing. These findings indicate that STP modulates the dynamic responses of pallidal activity during electrical stimulation, and may contribute to a better understanding of the mechanism underlying deep brain stimulation like protocols.
Highlights
High-frequency deep brain stimulation (HF–DBS) in the globus pallidus internus (GPi) and subthalamic nucleus (STN) is a widely employed method for treating Parkinson’s disease (PD; Benabid, 2003) and other disorders associated with the basal ganglia (BG)
We applied the whole-cell configuration of the patch-clamp technique to evaluate the impact of short-term synaptic plasticity (STP) on the firing pattern of GP neurons during repetitive stimulation
We have previously shown that the whole-cell configuration did not alter significantly the spontaneous firing rate of GP neurons (Bugaysen et al, 2010)
Summary
High-frequency deep brain stimulation (HF–DBS) in the globus pallidus internus (GPi) and subthalamic nucleus (STN) is a widely employed method for treating Parkinson’s disease (PD; Benabid, 2003) and other disorders associated with the basal ganglia (BG). Other experimental (Hashimoto et al, 2003; Bar-Gad et al, 2004; Meissner et al, 2005; Montgomery and Gale, 2008; McCairn and Turner, 2009) and theoretical (McIntyre et al, 2004a; Johnson and McIntyre, 2008) studies have reported that stimulation leads to complex activation of the stimulated nucleus or its targets. HF–DBS has been shown to affect other firing pattern properties including oscillatory and bursty activity (Meissner et al, 2005; Montgomery, 2006; Hahn et al, 2008; Xu et al, 2008; McCairn and Turner, 2009). The accumulating evidence highlights the importance of both firing rate and pattern changes during stimulation
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