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Stimulation-induced inhibition of neuronal firing in human subthalamic nucleus

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Abstract

The subthalamic nucleus (STN) is an important component of the basal ganglia (BG) and plays a major role in the pathogenesis of Parkinson’s disease (PD). Hyperactivity of STN as a consequence of the loss of dopaminergic inputs to the BG is believed to be a major factor in producing the motor symptoms of PD. High-frequency (HF) deep brain stimulation (DBS) of the STN has recently become an important treatment in PD patients where medications no longer provide satisfactory therapy. However, the mechanisms underlying DBS therapy are unknown, and there is seemingly conflicting data suggesting inhibition or excitation of STN neurons. This study directly examined the effects of stimulation in STN on the activity of STN neurons in PD patients during functional stereotactic mapping prior to insertion of DBS electrodes. Electrical stimulation in STN was investigated in twelve PD patients by recording the neural activity of a cell in STN with one electrode while applying current pulses through a second electrode located about 600 µm away. Stimulation at high frequencies (100–300 Hz) was found to produce inhibition following the stimulus train in 42% of the 60 cells tested. Inhibition during the train was seen in 13 of 15 neurons where it was possible to detect such activity. Furthermore, in 44% of the cases where HF stimulation produced inhibition there was an early inhibition followed by rebound excitation and a further inhibitory period, suggesting that the inhibitions observed are due to hyperpolarization. In eight of the 25 neurons inhibited by HF stimulation, the effects of single stimuli were determined and revealed that in seven of these there was an inhibitory period of 15–20 ms following each stimulus. Thus, the present findings suggest that local HF stimulation inhibits many STN neurons. However, these studies could not determine whether the stimulus also directly excited the cell and/or its axon, but other recent findings suggest that this is likely the case. Therefore, the overall effects of DBS stimulation in STN are likely to be inhibition of intrinsic and synaptically mediated activity, and its replacement by regular high-frequency firing.

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Acknowledgements

We wish to thank Helen Belina for expert assistance with the figures. Funding was provided by the U.S. National Institutes of Health (NS 40872) and Canadian Institutes of Health Research (MOP-42505). AML is a Canadian Institutes of Health Research clinician scientist.

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Authors and Affiliations

  1. Department of Physiology, Rm. 3305 Medical Sciences Building, University of Toronto, University Health Network, 1 King’s College Circle, Toronto, Ontario, M5S 1A8, Canada

    Mohammed Filali, William D. Hutchison, Vanessa N. Palter & Jonathan O. Dostrovsky

  2. Department of Surgery, University of Toronto, University Health Network, Toronto, Canada

    William D. Hutchison & Andres M. Lozano

  3. The Toronto Western Research Institute, University Health Network, Toronto, Canada

    William D. Hutchison, Andres M. Lozano & Jonathan O. Dostrovsky

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  1. Mohammed Filali
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  2. William D. Hutchison
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  3. Vanessa N. Palter
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  4. Andres M. Lozano
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  5. Jonathan O. Dostrovsky
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Correspondence to Jonathan O. Dostrovsky.

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Filali, M., Hutchison, W.D., Palter, V.N. et al. Stimulation-induced inhibition of neuronal firing in human subthalamic nucleus. Exp Brain Res 156, 274–281 (2004). https://doi.org/10.1007/s00221-003-1784-y

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  • DOI: https://doi.org/10.1007/s00221-003-1784-y

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