Cellular and Molecular NeuroscienceResearch PaperFrequency selectivity and dopamine-dependence of plasticity at glutamatergic synapses in the subthalamic nucleus
Highlights
▶We have studied synaptic plasticity of the cortico-subthalamic pathway. ▶We find HFS depresses cortico-subthalamic synapses but only in dopamine-depleted tissue. ▶LFS enhances transmission but only in dopamine-intact tissue. ▶Both these plasticity have presynaptic components. ▶Suggests dopamine-dependent changes in the synaptic weight of this pathway. ▶Suggests DBS promotes synaptic depression in Parkinson's disease.
Section snippets
Experimental procedures
All the animals in this study were used in accordance with the Animals (Scientific Procedures) Act, 1986 (UK) and the European Communities Council Directive (80/609/EEC).
Results
In the presence of picrotoxin (50 μM), stimulation within the internal capsule elicited a short-latency (monosynaptic) inward current that reversed around 0 mV and was blocked by glutamate receptor antagonists CNQX (10 μM) and d-AP5 (50 μM). At a stimulation frequency of 0.1 Hz, no potentiation or rundown of these synaptic responses and no changes in intrinsic properties such as resting membrane potential (monitored by changes in holding current) or input resistance were observed.
A previous
Discussion
We have shown that LFS, which mimics pathological cortically driven bursting activity in STN, promoted potentiation of glutamatergic (cortico-subthalamic) synaptic inputs but only in dopamine-intact tissue. Similarly, HFS promotes synaptic depression but only in dopamine-depleted tissue, indicating that the beneficial effects of DBS may be mediated, in part, by depression of cortico-subthalamic synapses (Fig. 5). Taken together, these results suggest that the synaptic weight of the
Acknowledgments
This work is supported by Parkinson's UK grant G-071 and The Medical Research Council, UK.
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2016, Experimental NeurologyCitation Excerpt :In another scenario, stimulation frequency and differences in BG tissue components including grey matter differences in PD (Reetz et al., 2009) may change the effect of stimulation. In a study by Yamawaki et al., LFS was found to potentiate cortico-subthalamic synaptic inputs in dopamine intact tissues, while HFS promoted synaptic depression in dopamine depleted tissue (Yamawaki et al., 2012). Correspondingly, they suggested that, similar to our results, the modulation of these pathways by STN DBS relies on the dopaminergic state in the tissue, and the frequency of stimulation used (Yamawaki et al., 2012).
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Present address: Department of Physiology, The Feinberg School of Medicine, Northwestern University, 303 E. Chicago Avenue, Chicago, IL 60611, USA.