Mechanisms of pallidal deep brain stimulation: Alteration of cortico-striatal synaptic communication in a dystonia animal model.

Abstract

Pallidal deep brain stimulation (DBS) is an important option for patients with severe dystonias, which are thought to arise from a disturbance in striatal control of the globus pallidus internus (GPi). The mechanisms of GPi-DBS are far from understood. Although a disturbance of striatal function is thought to play a key role in dystonia, the effects of DBS on cortico-striatal function are unknown. We hypothesised that DBS, via axonal backfiring, or indirectly via thalamic and cortical coupling, alters striatal function. We tested this hypothesis in the dtsz hamster, an animal model of inherited generalised, paroxysmal dystonia. Hamsters (dystonic and non-dystonic controls) were bilaterally implanted with stimulation electrodes in the GPi. DBS (130 Hz), and sham DBS, were performed in unanaesthetised animals for 3 h. Synaptic cortico-striatal field potentials, as well as miniature excitatory postsynaptic currents (mEPSC) and firing properties of medium spiny striatal neurones were recorded in brain slice preparations obtained immediately after EPN-DBS. The main findings were as follows: a. DBS increased cortico-striatal evoked responses in healthy, but not in dystonic tissue. b. Commensurate with this, DBS increased inhibitory control of these evoked responses in dystonic, and decreased inhibitory control in healthy tissue. c. Further, DBS reduced mEPSC frequency strongly in dystonic, and less prominently in healthy tissue, showing that also a modulation of presynaptic mechanisms is likely involved. d. Cellular properties of medium-spiny neurones remained unchanged. We conclude that DBS leads to dampening of cortico-striatal communication, and restores intrastriatal inhibitory tone.

• Authors: Marco Heerdegen, Monique Zwar, Denise Franz, Max Frederik Hörnschemeyer, Valentin Neubert, Franz Plocksties, Christoph Niemann, Dirk Timmermann, Christian Bahls, Ursula van Rienen, Maria Paap, Stefanie Perl, Anika Lüttig, Angelika Richter, Rüdiger Köhling
• Journal: Neurobiology of disease (Neurobiol Dis) Vol. 154 Pg. 105341 (07 2021) ISSN: 1095-953X [Electronic] United States
• PMID: 33753292 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.

Topics

• Animals
• Animals, Genetically Modified
• Cell Communication (physiology)
• Cerebral Cortex (physiology)
• Corpus Striatum (physiology)
• Cricetinae
• Deep Brain Stimulation (instrumentation, methods)
• Disease Models, Animal
• Dystonia (physiopathology, therapy)
• Electrodes, Implanted
• Excitatory Postsynaptic Potentials (physiology)
• Globus Pallidus (physiology)
• Mesocricetus
• Nerve Net (physiology)
• Synapses (physiology)