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A link between synaptic plasticity and reorganization of brain activity in Parkinson's disease.
Proc Natl Acad Sci U S A. 2021 01 19; 118(3)PN

Abstract

The link between synaptic plasticity and reorganization of brain activity in health and disease remains a scientific challenge. We examined this question in Parkinson's disease (PD) where functional up-regulation of postsynaptic D2 receptors has been documented while its significance at the neural activity level has never been identified. We investigated cortico-subcortical plasticity in PD using the oculomotor system as a model to study reorganization of dopaminergic networks. This model is ideal because this system reorganizes due to frontal-to-parietal shifts in blood oxygen level-dependent (BOLD) activity. We tested the prediction that functional activation plasticity is associated with postsynaptic dopaminergic modifications by combining positron emission tomography/functional magnetic resonance imaging to investigate striatal postsynaptic reorganization of dopamine D2 receptors (using 11C-raclopride) and neural activation in PD. We used covariance (connectivity) statistics at molecular and functional levels to probe striato-cortical reorganization in PD in on/off medication states to show that functional and molecular forms of reorganization are related. D2 binding across regions defined by prosaccades showed increased molecular connectivity between both caudate/putamen and hyperactive parietal eye fields in PD in contrast with frontal eye fields in controls, in line with the shift model. Concerning antisaccades, parietal-striatal connectivity dominated in again in PD, unlike frontal regions. Concerning molecular-BOLD covariance, a striking sign reversal was observed: PD patients showed negative frontal-putamen functional-molecular associations, consistent with the reorganization shift, in contrast with the positive correlations observed in controls. Follow-up analysis in off-medication PD patients confirmed the negative BOLD-molecular correlation. These results provide a link among BOLD responses, striato-cortical synaptic reorganization, and neural plasticity in PD.

Authors+Show Affiliations

Institute of Nuclear Sciences Applied to Health, University of Coimbra, 3000-548 Coimbra, Portugal. Coimbra Institute for Biomedical Imaging and Translational Research (CIBIT), University of Coimbra, 3000-548 Coimbra, Portugal. Faculty of Medicine, University of Coimbra, 3000-370 Coimbra, Portugal.Institute of Nuclear Sciences Applied to Health, University of Coimbra, 3000-548 Coimbra, Portugal. Champalimaud Centre for the Unknown, Champalimaud Foundation, 1400-038 Lisbon, Portugal.Institute of Nuclear Sciences Applied to Health, University of Coimbra, 3000-548 Coimbra, Portugal. Coimbra Institute for Biomedical Imaging and Translational Research (CIBIT), University of Coimbra, 3000-548 Coimbra, Portugal.Coimbra Institute for Biomedical Imaging and Translational Research (CIBIT), University of Coimbra, 3000-548 Coimbra, Portugal. Faculty of Medicine, University of Coimbra, 3000-370 Coimbra, Portugal. Neurology Department, Coimbra University Hospital Centre, 3004-561 Coimbra, Portugal.Coimbra Institute for Biomedical Imaging and Translational Research (CIBIT), University of Coimbra, 3000-548 Coimbra, Portugal. Faculty of Medicine, University of Coimbra, 3000-370 Coimbra, Portugal. Neurology Department, Coimbra University Hospital Centre, 3004-561 Coimbra, Portugal.Institute of Nuclear Sciences Applied to Health, University of Coimbra, 3000-548 Coimbra, Portugal; mcbranco@fmed.uc.pt. Coimbra Institute for Biomedical Imaging and Translational Research (CIBIT), University of Coimbra, 3000-548 Coimbra, Portugal. Faculty of Medicine, University of Coimbra, 3000-370 Coimbra, Portugal.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

33431672

Citation

Rebelo, Diliana, et al. "A Link Between Synaptic Plasticity and Reorganization of Brain Activity in Parkinson's Disease." Proceedings of the National Academy of Sciences of the United States of America, vol. 118, no. 3, 2021.
Rebelo D, Oliveira F, Abrunhosa A, et al. A link between synaptic plasticity and reorganization of brain activity in Parkinson's disease. Proc Natl Acad Sci U S A. 2021;118(3).
Rebelo, D., Oliveira, F., Abrunhosa, A., Januário, C., Lemos, J., & Castelo-Branco, M. (2021). A link between synaptic plasticity and reorganization of brain activity in Parkinson's disease. Proceedings of the National Academy of Sciences of the United States of America, 118(3). https://doi.org/10.1073/pnas.2013962118
Rebelo D, et al. A Link Between Synaptic Plasticity and Reorganization of Brain Activity in Parkinson's Disease. Proc Natl Acad Sci U S A. 2021 01 19;118(3) PubMed PMID: 33431672.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A link between synaptic plasticity and reorganization of brain activity in Parkinson's disease. AU - Rebelo,Diliana, AU - Oliveira,Francisco, AU - Abrunhosa,Antero, AU - Januário,Cristina, AU - Lemos,João, AU - Castelo-Branco,Miguel, PY - 2021/1/12/entrez PY - 2021/1/13/pubmed PY - 2021/5/13/medline KW - functional connectivity KW - functional magnetic resonance imaging KW - molecular imaging KW - positron emission tomography JF - Proceedings of the National Academy of Sciences of the United States of America JO - Proc Natl Acad Sci U S A VL - 118 IS - 3 N2 - The link between synaptic plasticity and reorganization of brain activity in health and disease remains a scientific challenge. We examined this question in Parkinson's disease (PD) where functional up-regulation of postsynaptic D2 receptors has been documented while its significance at the neural activity level has never been identified. We investigated cortico-subcortical plasticity in PD using the oculomotor system as a model to study reorganization of dopaminergic networks. This model is ideal because this system reorganizes due to frontal-to-parietal shifts in blood oxygen level-dependent (BOLD) activity. We tested the prediction that functional activation plasticity is associated with postsynaptic dopaminergic modifications by combining positron emission tomography/functional magnetic resonance imaging to investigate striatal postsynaptic reorganization of dopamine D2 receptors (using 11C-raclopride) and neural activation in PD. We used covariance (connectivity) statistics at molecular and functional levels to probe striato-cortical reorganization in PD in on/off medication states to show that functional and molecular forms of reorganization are related. D2 binding across regions defined by prosaccades showed increased molecular connectivity between both caudate/putamen and hyperactive parietal eye fields in PD in contrast with frontal eye fields in controls, in line with the shift model. Concerning antisaccades, parietal-striatal connectivity dominated in again in PD, unlike frontal regions. Concerning molecular-BOLD covariance, a striking sign reversal was observed: PD patients showed negative frontal-putamen functional-molecular associations, consistent with the reorganization shift, in contrast with the positive correlations observed in controls. Follow-up analysis in off-medication PD patients confirmed the negative BOLD-molecular correlation. These results provide a link among BOLD responses, striato-cortical synaptic reorganization, and neural plasticity in PD. SN - 1091-6490 UR - https://www.unboundmedicine.com/medline/citation/33431672/A_link_between_synaptic_plasticity_and_reorganization_of_brain_activity_in_Parkinson's_disease_ L2 - http://www.pnas.org/cgi/pmidlookup?view=long&pmid=33431672 DB - PRIME DP - Unbound Medicine ER -