scholarly journals Parkinson's disease uncovers an underlying sensitivity of subthalamic nucleus neurons to beta-frequency cortical input in vivo

2020 ◽  
Vol 146 ◽  
pp. 105119
Author(s):  
Magdalena K. Baaske ◽  
Eszter Kormann ◽  
Abbey B. Holt ◽  
Alessandro Gulberti ◽  
Colin G. McNamara ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Subthalamic Nucleus ◽  
Cortical Input ◽  
Beta Frequency

scholarly journals Parkinson’s disease uncovers an underlying sensitivity of subthalamic nucleus neurons to beta-frequency cortical input

2019 ◽  
Author(s):  
Magdalena K. Baaske ◽  
Eszter Kormann ◽  
Abbey B. Holt ◽  
Alessandro Gulberti ◽  
Colin G. McNamara ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Subthalamic Nucleus ◽  
Full Range ◽  
Spike Timing ◽  
Cortical Stimulation ◽  
Dopamine Depletion ◽  
Indirect Pathway ◽  
Cortical Input ◽  
Beta Frequency

AbstractAbnormally 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 (12-35Hz), 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 PD patients undergoing deep brain stimulation surgery with recordings of identified STN neurons in anaesthetised rats. In PD patients, we demonstrate that a subset of STN neurons are strongly and selectively sensitive to fluctuations of cortical beta oscillations over time, linearly increasing their phase-locking strength with respect to full range of instantaneous amplitude. In rats, we probed the frequency response of STN neurons more precisely, by recording spikes evoked by short bursts of cortical stimulation with variable frequency (4-40Hz) and constant amplitude. In both healthy and dopamine-depleted animals, only beta-frequency stimulation selectively led to a progressive reduction in the variability of spike timing through the stimulation train. 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.

scholarly journals Hyperbolic Modeling of Subthalamic Nucleus Cells to Investigate the Effect of Dopamine Depletion

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Mohammad Daneshzand ◽  
Miad Faezipour ◽  
Buket D. Barkana
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Subthalamic Nucleus ◽  
Activity Patterns ◽  
Dopamine Depletion ◽  
Computationally Efficient ◽  
Proposed Model ◽  
Parameter Modification ◽  
Simple Parameter

To investigate how different types of neurons can produce well-known spiking patterns, a new computationally efficient model is proposed in this paper. This model can help realize the neuronal interconnection issues. The model can demonstrate various neuronal behaviors observed in vivo through simple parameter modification. The behaviors include tonic and phasic spiking, tonic and phasic bursting, class 1 and class 2 excitability, rebound spike, rebound burst, subthreshold oscillation, and accommodated spiking along with inhibition neuron responses. Here, we investigate the neuronal spiking patterns in Parkinson’s disease through our proposed model. Abnormal pattern of subthalamic nucleus in Parkinson’s disease can be studied through variations in the shape and frequency of firing patterns. Our proposed model introduces mathematical equations, where these patterns can be derived and clearly differentiated from one another. The irregular and arrhythmic behaviors of subthalamic nucleus firing pattern under normal conditions can easily be transformed to those caused by Parkinson’s disease through simple parameter modifications in the proposed model. This model can explicitly show the change of neuronal activity patterns in Parkinson’s disease, which may eventually lead to effective treatment with deep brain stimulation devices.

scholarly journals Subthalamic nucleus activity dynamics and limb movement prediction in Parkinson’s disease

Brain ◽  
2020 ◽  
Vol 143 (2) ◽  
pp. 582-596 ◽  
Author(s):  
Saed Khawaldeh ◽  
Gerd Tinkhauser ◽  
Syed Ahmar Shah ◽  
Katrin Peterman ◽  
Ines Debove ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Basal Ganglia ◽  
Subthalamic Nucleus ◽  
Local Field ◽  
Local Field Potential ◽  
Field Potential ◽  
Beta Frequency Band ◽  
Potential Activity ◽  
Beta Frequency

Abstract Whilst exaggerated bursts of beta frequency band oscillatory synchronization in the subthalamic nucleus have been associated with motor impairment in Parkinson’s disease, a plausible mechanism linking the two phenomena has been lacking. Here we test the hypothesis that increased synchronization denoted by beta bursting might compromise information coding capacity in basal ganglia networks. To this end we recorded local field potential activity in the subthalamic nucleus of 18 patients with Parkinson’s disease as they executed cued upper and lower limb movements. We used the accuracy of local field potential-based classification of the limb to be moved on each trial as an index of the information held by the system with respect to intended action. Machine learning using the naïve Bayes conditional probability model was used for classification. Local field potential dynamics allowed accurate prediction of intended movements well ahead of their execution, with an area under the receiver operator characteristic curve of 0.80 ± 0.04 before imperative cues when the demanded action was known ahead of time. The presence of bursts of local field potential activity in the alpha, and even more so, in the beta frequency band significantly compromised the prediction of the limb to be moved. We conclude that low frequency bursts, particularly those in the beta band, restrict the capacity of the basal ganglia system to encode physiologically relevant information about intended actions. The current findings are also important as they suggest that local subthalamic activity may potentially be decoded to enable effector selection, in addition to force control in restorative brain-machine interface applications.

scholarly journals Role of 5-HT1A Receptor in Vilazodone-Mediated Suppression of L-DOPA-Induced Dyskinesia and Increased Responsiveness to Cortical Input in Striatal Medium Spiny Neurons in an Animal Model of Parkinson’s Disease

Molecules ◽  
2021 ◽  
Vol 26 (19) ◽  
pp. 5790
Author(s):  
Feras Altwal ◽  
Fernando E. Padovan-Neto ◽  
Alexandra Ritger ◽  
Heinz Steiner ◽  
Anthony R. West
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Selective Serotonin Reuptake Inhibitors ◽  
Partial Agonist ◽  
Critical Role ◽  
Medium Spiny Neurons ◽  
Cortical Input ◽  
Spiny Neurons ◽  
Underlying Mechanisms

L-DOPA therapy in Parkinson’s disease (PD) is limited due to emerging L-DOPA-induced dyskinesia. Research has identified abnormal dopamine release from serotonergic (5-HT) terminals contributing to this dyskinesia. Selective serotonin reuptake inhibitors (SSRIs) or 5-HT receptor (5-HTr) agonists can regulate 5-HT activity and attenuate dyskinesia, but they often also produce a loss of the antiparkinsonian efficacy of L-DOPA. We investigated vilazodone, a novel multimodal 5-HT agent with SSRI and 5-HTr1A partial agonist properties, for its potential to reduce dyskinesia without interfering with the prokinetic effects of L-DOPA, and underlying mechanisms. We assessed vilazodone effects on L-DOPA-induced dyskinesia (abnormal involuntary movements, AIMs) and aberrant responsiveness to corticostriatal drive in striatal medium spiny neurons (MSNs) measured with in vivo single-unit extracellular recordings, in the 6-OHDA rat model of PD. Vilazodone (10 mg/kg) suppressed all subtypes (axial, limb, orolingual) of AIMs induced by L-DOPA (5 mg/kg) and the increase in MSN responsiveness to cortical stimulation (shorter spike onset latency). Both the antidyskinetic effects and reversal in MSN excitability by vilazodone were inhibited by the 5-HTr1A antagonist WAY-100635, demonstrating a critical role for 5-HTr1A in these vilazodone actions. Our results indicate that vilazodone may serve as an adjunct therapeutic for reducing dyskinesia in patients with PD.

In vivo multimodal (MRI, SPECT) imaging of the 6-OHDA rat model for Parkinson's disease correlated with behavior and histology

2005 ◽  
Vol 25 (1_suppl) ◽  
pp. S392-S392
Author(s):  
Nadja Van Camp ◽  
Koen Van Laere ◽  
Ruth Vreys ◽  
Marleen Verhoye ◽  
Erwin Lauwers ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Rat Model ◽  
Spect Imaging ◽  
Multimodal Mri

Pharmacological treatment with L-DOPA may reduce striatal dopamine transporter binding in in vivo imaging studies

2016 ◽  
Vol 55 (01) ◽  
pp. 21-28 ◽  
Author(s):  
C. Antke ◽  
H. Hautzel ◽  
H.-W. Mueller ◽  
S. Nikolaus
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Binding Sites ◽  
Human Subjects ◽  
Synaptic Cleft ◽  
Presynaptic Terminal ◽  
Imaging Studies ◽  
Psychiatric Conditions ◽  
Da Release

SummaryNumerous neurologic and psychiatric conditions are treated with pharmacological compounds, which lead to an increase of synaptic dopamine (DA) levels. One example is the DA precursor L-3,4-dihydroxyphenylalanine (L-DOPA), which is converted to DA in the presynaptic terminal. If the increase of DA concentrations in the synaptic cleft leads to competition with exogenous radioligands for presynaptic binding sites, this may have implications for DA transporter (DAT) imaging studies in patients under DAergic medication.This paper gives an overview on those findings, which, so far, have been obtained on DAT binding in human Parkinson’s disease after treatment with L-DOPA. Findings, moreover, are related to results obtained on rats, mice or non-human primates. Results indicate that DAT imaging may be reduced in the striata of healthy animals, in the unlesioned striata of animal models of unilateral Parkinson’s disease and in less severly impaired striata of Parkinsonian patients, if animal or human subjects are under acute or subchronic treatment with L-DOPA. If also striatal DAT binding is susceptible to alterations of synaptic DA levels, this may allow to quantify DA reuptake in analogy to DA release by assessing the competition between endogenous DA and the administered exogenous DAT radioligand.

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