TY - JOUR
T1 - Parkinson's disease uncovers an underlying sensitivity of subthalamic nucleus neurons to beta-frequency cortical input in vivo
AU - Baaske, Magdalena K.
AU - Kormann, Eszter
AU - Holt, Abbey B.
AU - Gulberti, Alessandro
AU - McNamara, Colin G.
AU - Pötter-Nerger, Monika
AU - Westphal, Manfred
AU - Engel, Andreas K.
AU - Hamel, Wolfgang
AU - Brown, Peter
AU - Moll, Christian K.E.
AU - Sharott, Andrew
N1 - Funding Information:
The authors would like to thank all the patients who participated in this study. This work was supported by the Medical Research Council UK (MRC; award MC_UU_12024/1 to A.S. and P.B. and MC_UU_00003/6 to A.S.) and by a grant from the Deutsche Forschungsgemeinschaft (SFB 936, projects A2/A3 and C8 to A.K.E. and C.K.E.M./M.P.-N., respectively). E.K. was supported by University of Oxford Clarendon Fund Scholarships . CGM was supported by a Wellcome Trust Fellowship ( 209120/Z/17/Z ).
Publisher Copyright:
© 2020 The Authors
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/12
Y1 - 2020/12
N2 - 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-ganglia-network 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.
AB - 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-ganglia-network 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.
UR - http://www.scopus.com/inward/record.url?scp=85092272905&partnerID=8YFLogxK
UR - https://www.mendeley.com/catalogue/2ded0e91-3108-38b1-819b-e08897c81fe1/
U2 - 10.1016/j.nbd.2020.105119
DO - 10.1016/j.nbd.2020.105119
M3 - Journal articles
C2 - 32991998
AN - SCOPUS:85092272905
SN - 0969-9961
VL - 146
SP - 105119
JO - Neurobiology of Disease
JF - Neurobiology of Disease
M1 - 105119
ER -