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

NEUROBIOLOGY OF DISEASE

卷:154

Article

Heerdegen, Marco¹  Zwar, Monique¹  Franz, Denise¹  Hoernschemeyer, Julia¹  Neubert, Valentin¹  Plocksties, Franz²  Niemann, Christoph²  Timmermann, Dirk²  Bahls, Christian³  van Rienen, Ursula^3,5  Paap, Maria⁴  Perl, Stefanie⁴  Luettig, Anika⁴  Richter, Angelika⁴  Koehling, Rudiger^1,6 

[1] Rostock Univ, Med Ctr, Oscar Langendorff Inst, Gertrudenstr 9, D-18057 Rostock, Germany

[2] Univ Rostock, Fac Comp Sci & Elect Engn, Inst Appl Microelect & Comp Engn, Rostock, Germany

[3] Univ Rostock, Fac Comp Sci & Elect Engn, Inst Gen Elect Engn, Rostock, Germany

[4] Univ Leipzig, Fac Vet Med, Inst Pharmacol Pharm & Toxicol, Leipzig, Germany

[5] Univ Rostock, Dept Life Light & Matter, Rostock, Germany

[6] Univ Rostock, Dept Ageing Individuals & Soc, Rostock, Germany

关键词: Deep brain stimulation;    Globus pallidus;    Dystonia;    Inhibition;    Medium spiny neurones;    Basal ganglia;    Cortico-striatal projections;   

DOI  :  10.1016/j.nbd.2021.105341

来源: Elsevier

【 摘 要 】

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.