Synaptic plasticity in rat subthalamic nucleus induced by high‐frequency stimulation

The technique of deep brain stimulation (DBS) has become a preferred surgical choice for the treatment of advanced Parkinson's disease. The subthalamic nucleus (STN) is presently the most promising target for such DBS. In this study, whole‐cell patch‐clamp recordings were made from 46 STN neurons in rat brain slices to examine the effect of high‐frequency stimulation (HFS) of the STN on glutamatergic synaptic transmission in STN neurons. HFS, consisting of trains of stimuli at a frequency of 100 Hz for 1 min, produced three types of synaptic plasticity in 17 STN neurons. First, HFS of the STN induced short‐term potentiation (STP) of evoked postsynaptic current (EPSC) amplitude in four neurons. STP was associated with a reduction in the EPSC paired‐pulse ratio, suggesting a presynaptic site of action. Second, HFS of the STN generated long‐term potentiation (LTP) of EPSC amplitude in eight neurons. Although the EPSC paired‐pulse ratio was reduced transiently in the first 2 min following HFS, ratios measured 6–20 min after HFS were unchanged from control. This suggests that LTP is maintained by a postsynaptic mechanism. Third, HFS produced long‐term depression (LTD) of EPSC amplitude in five STN neurons. LTD was associated with a significant increase in EPSC paired‐pulse ratios, indicating a presynaptic site of action. These results suggest that HFS can produce long‐term changes in the efficacy of synaptic transmission in the STN. HFS‐induced synaptic plasticity might be one mechanism underlying the effectiveness of DBS in the STN as a treatment of advanced Parkinson's disease. Synapse 50:314–319, 2003. © 2003 Wiley‐Liss, Inc.

[1]  M. Dichter,et al.  Calcium-dependent Paired-pulse Facilitation of Miniature Epsc Frequency Accompanies Depression of Epscs at Hippocampal Synapses in Culture , 1996 .

[2]  S. Johnson,et al.  Presynaptic GABAB receptors inhibit synaptic inputs to rat subthalamic neurons , 2001, Neuroscience.

[3]  M. Randić,et al.  Long-term potentiation and long-term depression of primary afferent neurotransmission in the rat spinal cord , 1993, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[4]  H. Bergman,et al.  Reversal of experimental parkinsonism by lesions of the subthalamic nucleus. , 1990, Science.

[5]  P. Overton,et al.  Long-term potentiation at excitatory amino acid synapses on midbrain dopamine neurons. , 1999, Neuroreport.

[6]  C. Zorumski,et al.  Paired‐pulse modulation of fast excitatory synaptic currents in microcultures of rat hippocampal neurons. , 1995, The Journal of physiology.

[7]  R. Nicoll,et al.  Two Distinct Forms of Long-Term Depression Coexist in CA1 Hippocampal Pyramidal Cells , 1997, Neuron.

[8]  A. Benabid,et al.  Electrical stimulation of the subthalamic nucleus in advanced Parkinson's disease. , 1998, The New England journal of medicine.

[9]  G. Collingridge,et al.  A characterisation of long‐term depression induced by metabotropic glutamate receptor activation in the rat hippocampus in vitro , 2001, The Journal of physiology.

[10]  T. Bliss,et al.  A synaptic model of memory: long-term potentiation in the hippocampus , 1993, Nature.

[11]  F. Windels,et al.  Effects of high frequency stimulation of subthalamic nucleus on extracellular glutamate and GABA in substantia nigra and globus pallidus in the normal rat , 2000, The European journal of neuroscience.

[12]  Carlos M. Magariños‐Ascone,et al.  Subthalamic neuron activity related to tremor and movement in Parkinson's disease , 2000, The European journal of neuroscience.

[13]  J. Vitek.  Mechanisms of deep brain stimulation: Excitation or inhibition , 2002, Movement disorders : official journal of the Movement Disorder Society.

[14]  Abdelhamid Benazzouz,et al.  Responses of substantia nigra pars reticulata and globus pallidus complex to high frequency stimulation of the subthalamic nucleus in rats: electrophysiological data , 1995, Neuroscience Letters.

[15]  Abdelhamid Benazzouz,et al.  High frequency stimulation of the STN influences the activity of dopamine neurons in the rat , 2000, Neuroreport.

[16]  A. Lang,et al.  Double-blind evaluation of subthalamic nucleus deep brain stimulation in advanced Parkinson's disease , 1998, Neurology.

[17]  W. Regehr,et al.  Delayed Release of Neurotransmitter from Cerebellar Granule Cells , 1998, The Journal of Neuroscience.

[18]  S. Johnson,et al.  Presynaptic dopamine D2 and muscarine M3 receptors inhibit excitatory and inhibitory transmission to rat subthalamic neurones in vitro , 2000, The Journal of physiology.

[19]  N. Kato.  Dependence of long-term depression on postsynaptic metabotropic glutamate receptors in visual cortex. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[20]  M. Guenot,et al.  Subthalamic nucleus stimulation in Parkinson's disease , 2002, Journal of Neurology.

[21]  R. Albin,et al.  The pathophysiology of chorea/ballism and Parkinsonism. , 1995, Parkinsonism & related disorders.

[22]  P. Calabresi,et al.  Long-term synaptic depression in the striatum: physiological and pharmacological characterization , 1992, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[23]  A. Benabid,et al.  Effect on parkinsonian signs and symptoms of bilateral subthalamic nucleus stimulation , 1995, The Lancet.

[24]  D. Lovinger,et al.  Short- and long-term synaptic depression in rat neostriatum. , 1993, Journal of neurophysiology.

[25]  S. Johnson,et al.  Presynaptic inhibition of synaptic transmission by adenosine in rat subthalamic nucleus in vitro , 2003, Neuroscience.

[26]  S. Kombian,et al.  Short-term potentiation of miniature excitatory synaptic currents causes excitation of supraoptic neurons. , 2000, Journal of neurophysiology.

[27]  G. Paxinos,et al.  The Rat Brain in Stereotaxic Coordinates , 1983 .

[28]  K. Mewes,et al.  The subthalamic nucleus in Parkinson's disease: somatotopic organization and physiological characteristics. , 2001, Brain : a journal of neurology.

[29]  R. Nicoll,et al.  Contrasting properties of two forms of long-term potentiation in the hippocampus , 1995, Nature.

[30]  O. Macadar,et al.  High-frequency stimulation of the subthalamic nucleus silences subthalamic neurons: a possible cellular mechanism in Parkinson’s disease , 2002, Neuroscience.

[31]  G. Collingridge,et al.  Excitatory amino acids in synaptic transmission in the Schaffer collateral‐commissural pathway of the rat hippocampus. , 1983, The Journal of physiology.

[32]  H. Dodt,et al.  Neocortical Long-Term Potentiation and Long-Term Depression: Site of Expression Investigated by Infrared-Guided Laser Stimulation , 2002, The Journal of Neuroscience.

[33]  D. Tank,et al.  Presynaptic Calcium in Transmitter Release and Posttetanic Potentiation a , 1991, Annals of the New York Academy of Sciences.

[34]  A. Benabid,et al.  High-frequency stimulation of the subthalamic nucleus suppresses experimental resting tremor in the monkey , 1999, Neuroscience.

[35]  B Bioulac,et al.  Reversal of Rigidity and Improvement in Motor Performance by Subthalamic High‐frequency Stimulation in MPTP‐treated Monkeys , 1993, The European journal of neuroscience.

[36]  H. Kita,et al.  Electrical membrane properties of rat subthalamic neurons in an in vitro slice preparation , 1987, Brain Research.

[37]  S. Johnson,et al.  Presynaptic modulation of synaptic transmission by opioid receptor in rat subthalamic nucleus in vitro , 2002, The Journal of physiology.

[38]  R. J. Allan,et al.  Neurophysiological identification of the subthalamic nucleus in surgery for Parkinson's disease , 1998, Annals of neurology.