scholarly journals Dopamine and Striatal Neuron Firing Respond to Frequency-Dependent DBS Detected by Microelectrode Arrays in the Rat Model of Parkinson’s Disease

Biosensors ◽  
2020 ◽  
Vol 10 (10) ◽  
pp. 136
Author(s):  
Guihua Xiao ◽  
Yilin Song ◽  
Yu Zhang ◽  
Yu Xing ◽  
Shengwei Xu ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Firing Rate ◽  
Microelectrode Arrays ◽  
Cellular Level ◽  
Striatal Neuron ◽  
Neuron Firing ◽  
Efficient Treatment ◽  
Neural Spike ◽  
Spike Firing

(1) Background: Deep brain stimulation (DBS) is considered as an efficient treatment method for alleviating motor symptoms in Parkinson’s disease (PD), while different stimulation frequency effects on the specific neuron patterns at the cellular level remain unknown. (2) Methods: In this work, nanocomposites-modified implantable microelectrode arrays (MEAs) were fabricated to synchronously record changes of dopamine (DA) concentration and striatal neuron firing in the striatum during subthalamic nucleus DBS, and different responses of medium spiny projecting neurons (MSNs) and fast spiking interneurons (FSIs) to DBS were analyzed. (3) Results: DA concentration and striatal neuron spike firing rate showed a similar change as DBS frequency changed from 10 to 350 Hz. Note that the increases in DA concentration (3.11 ± 0.67 μM) and neural spike firing rate (15.24 ± 2.71 Hz) were maximal after the stimulation at 100 Hz. The MSNs firing response to DBS was significant, especially at 100 Hz, while the FSIs remained stable after various stimulations. (4) Conclusions: DBS shows the greatest regulatory effect on DA concentration and MSNs firing rate at 100 Hz stimulation. This implantable MEA in the recording of the neurotransmitter and neural spike pattern response to DBS provides a new insight to understand the mechanism of PD at the cellular level.

scholarly journals Changes in excitability properties of ventromedial motor thalamic neurons in 6-OHDA lesioned mice

2020 ◽  
Author(s):  
Edyta K Bichler ◽  
Francesco Cavarretta ◽  
Dieter Jaeger
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Basal Ganglia ◽  
Potassium Current ◽  
Cellular Level ◽  
Inhibitory Input ◽  
Dopamine Depletion ◽  
Thalamic Nuclei ◽  
Adult Mice ◽  
Motor Thalamus

AbstractThe activity of basal ganglia input receiving motor thalamus (BGMT) makes a critical impact on motor cortical processing, but modification in BGMT processing with Parkinsonian conditions have not be investigated at the cellular level. Such changes may well be expected due to homeostatic regulation of neural excitability in the presence of altered synaptic drive with dopamine depletion. We addressed this question by comparing BGMT properties in brain slice recordings between control and unilaterally 6-OHDA treated adult mice. At a minimum of 1 month post 6-OHDA treatment, BGMT neurons showed a highly significant increase in intrinsic excitability, which was primarily due to a decrease in M-type potassium current. BGMT neurons after 6-OHDA treatment also showed an increase in T-type calcium rebound spikes following hyperpolarizing current steps. Biophysical computer modeling of a thalamic neuron demonstrated that an increase in rebound spiking can also be accounted for by a decrease in the M-type potassium current. Modeling also showed that an increase in sag with hyperpolarizing steps found after 6-OHDA treatment could in part but not fully be accounted for by the decrease in M-type current. These findings support the hypothesis that homeostatic changes in BGMT neural properties following 6-OHDA treatment likely influence the signal processing taking place in basal ganglia thalamocortical processing in Parkinson’s disease.Significance StatementOur investigation of the excitability properties of neurons in the basal ganglia input receiving motor thalamus (BGMT) is significant because they are likely to be different from properties in other thalamic nuclei due to the additional inhibitory input stream these neurons receive. Further, they are important to understand the role of BGMT in the dynamic dysfunction of cortico – basal ganglia circuits in Parkinson’s disease. We provide clear evidence that after 6-OHDA treatment of mice important homeostatic changes occur in the intrinsic properties of BGMT neurons. Specifically we identify the M-type potassium current as an important thalamic excitability regulator in the parkinsonian state.

scholarly journals Modeling Parkinson’s Disease Using Induced Pluripotent Stem Cells

2020 ◽  
Vol 2020 ◽  
pp. 1-15
Author(s):  
Xinchao Hu ◽  
Chengyuan Mao ◽  
Liyuan Fan ◽  
Haiyang Luo ◽  
Zhengwei Hu ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Stem Cells ◽  
Parkinson's Disease ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Molecular Mechanisms ◽  
Cellular Level ◽  
Patient Specific ◽  
Ubiquitin Protein Ligase ◽  
Induced Pluripotent

Parkinson’s disease (PD) is the second most common neurodegenerative disease. The molecular mechanisms of PD at the cellular level involve oxidative stress, mitochondrial dysfunction, autophagy, axonal transport, and neuroinflammation. Induced pluripotent stem cells (iPSCs) with patient-specific genetic background are capable of directed differentiation into dopaminergic neurons. Cell models based on iPSCs are powerful tools for studying the molecular mechanisms of PD. The iPSCs used for PD studies were mainly from patients carrying mutations in synuclein alpha (SNCA), leucine-rich repeat kinase 2 (LRRK2), PTEN-induced putative kinase 1 (PINK1), parkin RBR E3 ubiquitin protein ligase (PARK2), cytoplasmic protein sorting 35 (VPS35), and variants in glucosidase beta acid (GBA). In this review, we summarized the advances in molecular mechanisms of Parkinson’s disease using iPSC models.

Internal Pallidal Neuronal Activity During Mild Drug-Related Dyskinesias in Parkinson's Disease: Decreased Firing Rates and Altered Firing Patterns

2007 ◽  
Vol 97 (4) ◽  
pp. 2627-2641 ◽  
Author(s):  
J. I. Lee ◽  
L. Verhagen Metman ◽  
S. Ohara ◽  
P. M. Dougherty ◽  
J. H. Kim ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Firing Rate ◽  
Spike Trains ◽  
Neuronal Firing ◽  
Low Doses ◽  
Significant Group ◽  
Firing Patterns ◽  
Firing Rates ◽  
Before And After

The neuronal basis of hyperkinetic movement disorders has long been unclear. We now test the hypothesis that changes in the firing pattern of neurons in the globus pallidus internus (GPi) are related to dyskinesias induced by low doses of apomorphine in patients with advanced Parkinson's disease (PD). During pallidotomy for advanced PD, the activity of single neurons was studied both before and after administration of apomorphine at doses just adequate to induce dyskinesias (21 neurons, 17 patients). After the apomorphine injection, these spike trains demonstrated an initial fall in firing from baseline. In nine neurons, the onset of on was simultaneous with that of dyskinesias. In these spike trains, the initial fall in firing rate preceded and was larger than the fall at the onset of on with dyskinesias. Among the three neurons in which the onset of on occurred before that of dyskinesias, the firing rate did not change at the time of onset of dyskinesias. After injection of apomorphine, dyskinesias during on with dyskinesias often fluctuated between transient periods with dyskinesias and those without. Average firing rates were not different between these two types of transient periods. Transient periods with dyskinesias were characterized by interspike interval (ISI) independence, stationary spike trains, and higher variability of ISIs. A small but significant group of neurons demonstrated recurring ISI patterns during transient periods of on with dyskinesias. These results suggest that mild dyskinesias resulting from low doses of apomorphine are related to both low GPi neuronal firing rates and altered firing patterns.

Effects of Apomorphine on Subthalamic Nucleus and Globus Pallidus Internus Neurons in Patients With Parkinson's Disease

2001 ◽  
Vol 86 (1) ◽  
pp. 249-260 ◽  
Author(s):  
R. Levy ◽  
J. O. Dostrovsky ◽  
A. E. Lang ◽  
E. Sime ◽  
W. D. Hutchison ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Firing Rate ◽  
Globus Pallidus ◽  
Subthalamic Nucleus ◽  
Current Model ◽  
Passive Movement ◽  
Spontaneous Discharge ◽  
Dopamine Receptor Agonist ◽  
Firing Rates

This study examines the effect of apomorphine (APO), a nonselective D1- and D2-dopamine receptor agonist, on the firing activity of neurons in the subthalamic nucleus (STN) and internal segment of the globus pallidus (GPi) in patients with Parkinson's disease (PD). Single-unit microelectrode recordings were conducted in 13 patients undergoing implantation of deep brain stimulation electrodes in STN and 6 patients undergoing a pallidotomy. Doses of APO (2.5–8 mg) were sufficient to produce anon state, but not intended to induce dyskinetic movements. Following baseline recordings from a single neuron, APO was administered and the activity of the neuron followed for an average of 15 min. The spontaneous discharge of neurons encountered before ( n = 309), during ( n = 146, 10–60 min), and after the effect of APO had waned ( n = 127, >60 min) was also sampled, and the response to passive joint movements was noted. In both nuclei, APO increased the overall proportion of spikes in burst discharges (as detected with Poisson “surprise” analysis), and a greater proportion of cells with an irregular discharge pattern was observed. APO significantly decreased the overall firing rates of GPi neurons ( P < 0.01), but there was no change in the overall firing rate of neurons in the STN ( P = 0.68). However, the mean firing rates of STN neurons during APO-induced movements (choreic or dystonic dyskinesias) that occurred in four patients were significantly lower thanoff-period baseline values ( P < 0.05). Concurrent with a reduction in limb tremor, the percentage of cells with tremor-related activity (TCs) was found to be significantly reduced from 19 to 6% in the STN and 14 to 0% in the GPi following APO administration. APO also decreased the firing rate of STN TCs ( P < 0.05). During the off state, more than 15% of neurons tested (STN = 93, GPi = 63) responded to passive movement of two or more joints. After APO, this proportion decreased significantly to 7% of STN cells and 4% of GPi cells (STN = 28, GPi = 26). These findings suggest that the APO-induced amelioration of parkinsonian symptoms is not solely due to a decrease in overall activity in the GPi or STN as predicted by the current model of basal ganglia function in PD.

scholarly journals Subthalamic nucleus neuronal firing rate increases with Parkinson's disease progression

2011 ◽  
Vol 26 (9) ◽  
pp. 1657-1662 ◽  
Author(s):  
Michael S. Remple ◽  
Courtney H. Bradenham ◽  
C. Chris Kao ◽  
P. David Charles ◽  
Joseph S. Neimat ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Firing Rate ◽  
Disease Progression ◽  
Subthalamic Nucleus ◽  
Neuronal Firing ◽  
Neuronal Firing Rate

scholarly journals Deep Brain Stimulation Does Not Silence Neurons in Subthalamic Nucleus in Parkinson's Patients

2010 ◽  
Vol 103 (2) ◽  
pp. 962-967 ◽  
Author(s):  
Jonathan D. Carlson ◽  
Daniel R. Cleary ◽  
Justin S. Cetas ◽  
Mary M. Heinricher ◽  
Kim J. Burchiel
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Deep Brain Stimulation ◽  
Basal Ganglia ◽  
Firing Rate ◽  
Subthalamic Nucleus ◽  
Brain Stimulation ◽  
Animal Studies ◽  
Stimulation Parameters ◽  
Deep Brain

Two broad hypotheses have been advanced to explain the clinical efficacy of deep brain stimulation (DBS) in the subthalamic nucleus (STN) for treatment of Parkinson's disease. One is that stimulation inactivates STN neurons, producing a functional lesion. The other is that electrical stimulation activates the STN output, thus “jamming” pathological activity in basal ganglia-corticothalamic circuits. Evidence consistent with both concepts has been adduced from modeling and animal studies, as well as from recordings in patients. However, the stimulation parameters used in many recording studies have not been well matched to those used clinically. In this study, we recorded STN activity in patients with Parkinson's disease during stimulation delivered through a clinical DBS electrode using standard therapeutic stimulus parameters. A microelectrode was used to record the firing of a single STN neuron during DBS (3–5 V, 80–200 Hz, 90- to 200-μs pulses; 33 neurons/11 patients). Firing rate was unchanged during the stimulus trains, and the recorded neurons did not show prolonged (s) changes in firing rate on termination of the stimulation. However, a brief (∼1 ms), short-latency (6 ms) postpulse inhibition was seen in 10 of 14 neurons analyzed. A subset of neurons displayed altered firing patterns, with a predominant shift toward random firing. These data do not support the idea that DBS inactivates the STN and are instead more consistent with the hypothesis that this stimulation provides a null signal to basal ganglia-corticothalamic circuitry that has been altered as part of Parkinson's disease.

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