Please use this identifier to cite or link to this item:
Title: A link between synaptic plasticity and reorganization of brain activity in Parkinson's disease
Authors: Rebelo, Diliana 
Oliveira, Francisco 
Abrunhosa, Antero 
Januário, Cristina 
Lemos, João 
Castelo-Branco, Miguel 
Keywords: Functional connectivity; Functional magnetic resonance imaging
Issue Date: 19-Jan-2021
Publisher: National Academy of Sciences
Project: FCT/UID/4950/201 
Bial Foundation 252/18 
Serial title, monograph or event: PNAS - Proceedings of the National Academy of Sciences of the United States of America
Volume: 118
Issue: 3
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.
ISSN: 0027-8424
DOI: 10.1073/pnas.2013962118
Rights: openAccess
Appears in Collections:FMUC Medicina - Artigos em Revistas Internacionais

Files in This Item:
File Description SizeFormat
A link between synaptic plasticity and reorganization.pdf1.12 MBAdobe PDFView/Open
Show full item record


checked on Nov 9, 2022


checked on Dec 2, 2023

Page view(s)

checked on Nov 28, 2023


checked on Nov 28, 2023

Google ScholarTM




This item is licensed under a Creative Commons License Creative Commons