Abstract
Electrophysiological recordings performed in parkinsonian patients and animal models have confirmed the occurrence of alterations in firing rate and pattern of basal ganglia neurons, but the outcome of these changes in thalamo-cortical networks remains unclear. Using rats rendered parkinsonian, we investigated, at a cellular level in vivo, the electrophysiological changes induced in the pyramidal cells of the motor cortex by the dopaminergic transmission interruption and further characterized the impact of high-frequency electrical stimulation of the subthalamic nucleus, a procedure alleviating parkinsonian symptoms. We provided evidence that a lesion restricted to the substantia nigra pars compacta resulted in a marked increase in the mean firing rate and bursting pattern of pyramidal neurons of the motor cortex. These alterations were underlain by changes of the electrical membranes properties of pyramidal cells including depolarized resting membrane potential and increased input resistance. The modifications induced by the dopaminergic loss were more pronounced in cortico-striatal than in cortico-subthalamic neurons. Furthermore, subthalamic nucleus high-frequency stimulation applied at parameters alleviating parkinsonian signs regularized the firing pattern of pyramidal cells and restored their electrical membrane properties.
Highlights
Parkinson’s disease (PD) motor symptoms including akinesia, rigidity and tremor result from the neurodegeneration of the nigro-striatal dopaminergic (DA) neurons
As assessed by tyrosine hydroxylase (TH) immunoreactivity (Fig. 1), the unilateral injection of 6-OHDA in the substantia nigra pars compacta (SNc) resulted in a complete loss of DA cell bodies located in the SNc but spared the ventral tegmental area (VTA)
Combining in vivo extra- and intracellular recordings, we investigated the effects of SNc lesions on the electrophysiological properties of identified pyramidal neurons from the motor cortex
Summary
Parkinson’s disease (PD) motor symptoms including akinesia, rigidity and tremor result from the neurodegeneration of the nigro-striatal dopaminergic (DA) neurons. Concerning the impact of STN HFS, functional cerebral imaging in PD patients during STN HFS revealed an overactivity of the thalamus as well as a reduction of primary motor and premotor cortices metabolic activity, an opposite effect to the expected result [19,20,21,22,23] In line with this finding, a pharmacological blockade of substantia nigra pars reticulata (SNr) activity induces an increased discharge of thalamocortical neurons resulting in a decreased firing rate of motor cortex pyramidal cells [24] suggesting a major implication of cortical inhibitory interneurons in the cortical consequences of changes in BG activity. The net impact on the motor cortex of DA loss and STN HFS are still unclear
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.