RT Journal Article
SR Electronic
T1 Beta-Band Oscillations without Pathways: the opposing Roles of D2 and D5 Receptors
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 161661
DO 10.1101/161661
A1 Jean F. Liénard
A1 Ignasi Cos
A1 Benoît Girard
YR 2017
UL http://biorxiv.org/content/early/2017/07/10/161661.abstract
AB Parkinson’s disease is characterized by the death of dopaminergic neurons and the emergence of strong β-band oscillations throughout the basal ganglia nuclei. According to the mainstream theory, this synchrony is mediated by a dopamine deficit within the striatum creating a functional imbalance between the D1-expressing medium spiny neurons, which project to the internal segment of the globus pallidus, and D2-expressing one, which target its external segment, and ultimately leads to oscillatory activity. However, anatomical evidence gathered in rodents and primates has shown that striatal neurons are for the most part not organized into independent populations differentially targeting the two segments of the globus pallidus, nor alternatively expressing D1 or D2 receptors, thus calling for an alternative mechanism through which the lack of dopamine may cause oscillations. Here we adopt a computational approach in which we investigate a model whose parameters are fit to an extensive set of anatomical and physiological constraints from non-human primates, including axonal transmission delays gathered from eight experimental studies. Investigating the lack of dopamine in this model revealed that in the absence of segregated pathways, β-band oscillations emerge as a consequence of the extra-striate dopaminergic receptors reduced activity. These oscillations are caused by synchronous activity within the external globus pallidus-subthalamic nucleus loop, and their frequency are modulated by the transmission delays between these nuclei. Our model delivers a parsimonious explanation of oscillations that does not require any external driving influence from cortex, nor specific medium spiny neuron properties.