Parkinson's disease uncovers an underlying sensitivity of subthalamic nucleus neurons to beta-frequency cortical input in vivo

NEUROBIOLOGY OF DISEASE

卷:146

Article

Baaske, Magdalena K.^1,2,3  Kormann, Eszter¹  Holt, Abbey B.¹  Gulberti, Alessandro⁴  McNamara, Colin G.¹  Poetter-Nerger, Monika⁵  Westphal, Manfred⁶  Engel, Andreas K.⁴  Hamel, Wolfgang⁶  Brown, Peter^1,2  Moll, Christian K. E.⁴  Sharott, Andrew¹ 

[1] Univ Oxford, Med Res Council Brain Network Dynam Unit, Nuffield Dept Clin Neurosci, Mansfield Rd, Oxford OX1 3TH, England

[2] Univ Lubeck, Dept Neurol, D-23538 Lubeck, Germany

[3] Univ Lubeck, Inst Neurogenet, D-23538 Lubeck, Germany

[4] Univ Med Ctr Hamburg Eppendorf, Dept Neurophysiol & Pathophysiol, D-20246 Hamburg, Germany

[5] Univ Med Ctr Hamburg Eppendorf, Dept Neurol, D-20246 Hamburg, Germany

[6] Univ Med Ctr Hamburg Eppendorf, Dept Neurosurg, D-20246 Hamburg, Germany

关键词: Cortex;    Beta oscillation;    Parkinson's disease;    STN neuron;    Synchronisation;   

DOI  :  10.1016/j.nbd.2020.105119

来源: Elsevier

【 摘 要 】

Abnormally sustained beta-frequency synchronisation between the motor cortex and subthalamic nucleus (STN) is associated with motor symptoms in Parkinson's disease (PD). It is currently unclear whether STN neurons have a preference for beta-frequency input (12-35 Hz), rather than cortical input at other frequencies, and how such a preference would arise following dopamine depletion. To address this question, we combined analysis of cortical and STN recordings from awake human PD patients undergoing deep brain stimulation surgery with recordings of identified STN neurons in anaesthetised rats. In these patients, we demonstrate that a subset of putative STN neurons is strongly and selectively sensitive to magnitude fluctuations of cortical beta oscillations over time, linearly increasing their phase-locking strength with respect to the full range of instantaneous amplitude in the beta-frequency range. In rats, we probed the frequency response of STN neurons in the cortico-basal-ganglianetwork more precisely, by recording spikes evoked by short bursts of cortical stimulation with variable frequency (4-40 Hz) and constant amplitude. In both healthy and dopamine-depleted rats, only beta-frequency stimulation led to a progressive reduction in the variability of spike timing through the stimulation train. This suggests, that the interval of beta-frequency input provides an optimal window for eliciting the next spike with high fidelity. We hypothesize, that abnormal activation of the indirect pathway, via dopamine depletion and/or cortical stimulation, could trigger an underlying sensitivity of the STN microcircuit to beta-frequency input.