Frequency selectivity and dopamine-dependence of plasticity at glutamatergic synapses in the subthalamic nucleus

Naoki Yamawaki, P.J. Magill, Stephen Hall, Gavin Woodhall, Ian Stanford

Research output: Contribution to journalArticle

Abstract

In Parkinson's disease, subthalamic nucleus (STN) neurons burst fire with increased periodicity and synchrony. This may entail abnormal release of glutamate, the major source of which in STN is cortical afferents. Indeed, the cortico-subthalamic pathway is implicated in the emergence of excessive oscillations, which are reduced, as are symptoms, by dopamine-replacement therapy or deep brain stimulation (DBS) targeted to STN. Here we hypothesize that glutamatergic synapses in the STN may be differentially modulated by low-frequency stimulation (LFS) and high-frequency stimulation (HFS), the latter mimicking deep brain stimulation. Recordings of evoked and spontaneous excitatory post synaptic currents (EPSCs) were made from STN neurons in brain slices obtained from dopamine-intact and chronically dopamine-depleted adult rats. HFS had no significant effect on evoked (e) EPSC amplitude in dopamine-intact slices (104.4±8.0%) but depressed eEPSCs in dopamine-depleted slices (67.8±6.2%). Conversely, LFS potentiated eEPSCs in dopamine-intact slices (126.4±8.1%) but not in dopamine-depleted slices (106.7±10.0%). Analyses of paired-pulse ratio, coefficient of variation, and spontaneous EPSCs suggest that the depression and potentiation have a presynaptic locus of expression. These results indicate that the synaptic efficacy in dopamine-intact tissue is enhanced by LFS. Furthermore, the synaptic efficacy in dopamine-depleted tissue is depressed by HFS. Therefore the therapeutic effects of DBS in Parkinson's disease appear mediated, in part, by glutamatergic cortico-subthalamic synaptic depression and implicate dopamine-dependent increases in the weight of glutamate synapses, which would facilitate the transfer of pathological oscillations from the cortex.
LanguageEnglish
Article number22209920
Pages1-11
Number of pages11
JournalNeuroscience
Volume203
Early online date22 Dec 2011
DOIs
Publication statusPublished - 17 Feb 2012

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Subthalamic Nucleus
Synapses
Dopamine
Deep Brain Stimulation
Parkinson Disease
Glutamic Acid
Neurons
Therapeutic Uses
Periodicity
Weights and Measures

Keywords

  • subthalamic nucleus
  • primary motor cortex
  • 6-hyroxydopamine
  • deep brain stimulation

Cite this

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abstract = "In Parkinson's disease, subthalamic nucleus (STN) neurons burst fire with increased periodicity and synchrony. This may entail abnormal release of glutamate, the major source of which in STN is cortical afferents. Indeed, the cortico-subthalamic pathway is implicated in the emergence of excessive oscillations, which are reduced, as are symptoms, by dopamine-replacement therapy or deep brain stimulation (DBS) targeted to STN. Here we hypothesize that glutamatergic synapses in the STN may be differentially modulated by low-frequency stimulation (LFS) and high-frequency stimulation (HFS), the latter mimicking deep brain stimulation. Recordings of evoked and spontaneous excitatory post synaptic currents (EPSCs) were made from STN neurons in brain slices obtained from dopamine-intact and chronically dopamine-depleted adult rats. HFS had no significant effect on evoked (e) EPSC amplitude in dopamine-intact slices (104.4±8.0{\%}) but depressed eEPSCs in dopamine-depleted slices (67.8±6.2{\%}). Conversely, LFS potentiated eEPSCs in dopamine-intact slices (126.4±8.1{\%}) but not in dopamine-depleted slices (106.7±10.0{\%}). Analyses of paired-pulse ratio, coefficient of variation, and spontaneous EPSCs suggest that the depression and potentiation have a presynaptic locus of expression. These results indicate that the synaptic efficacy in dopamine-intact tissue is enhanced by LFS. Furthermore, the synaptic efficacy in dopamine-depleted tissue is depressed by HFS. Therefore the therapeutic effects of DBS in Parkinson's disease appear mediated, in part, by glutamatergic cortico-subthalamic synaptic depression and implicate dopamine-dependent increases in the weight of glutamate synapses, which would facilitate the transfer of pathological oscillations from the cortex.",
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Frequency selectivity and dopamine-dependence of plasticity at glutamatergic synapses in the subthalamic nucleus. / Yamawaki, Naoki; Magill, P.J.; Hall, Stephen; Woodhall, Gavin; Stanford, Ian.

In: Neuroscience, Vol. 203, 22209920, 17.02.2012, p. 1-11.

Research output: Contribution to journalArticle

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