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Potential mechanisms for imperfect synchronization in parkinsonian basal ganglia.

Park C, Rubchinsky LL - PLoS ONE (2012)

Bottom Line: However, dopamine also affects the cellular properties of neurons.The intermittent nature of the neural beta band synchrony in Parkinson's disease is achieved in the model due to the interplay of the timing of STN input to pallidum and pallidal neuronal dynamics, resulting in sensitivity of pallidal output to the phase of the arriving STN input.Thus the mechanism considered here (the change in firing pattern of subthalamic neurons through the dopamine-induced change of membrane properties) may be one of the potential mechanisms responsible for the generation of the intermittent synchronization observed in Parkinson's disease.

View Article: PubMed Central - PubMed

Affiliation: Department of Mathematical Sciences and Center for Mathematical Biosciences, Indiana University Purdue University Indianapolis, Indianapolis, IN, USA. 21cspark@gmail.com

ABSTRACT
Neural activity in the brain of parkinsonian patients is characterized by the intermittently synchronized oscillatory dynamics. This imperfect synchronization, observed in the beta frequency band, is believed to be related to the hypokinetic motor symptoms of the disorder. Our study explores potential mechanisms behind this intermittent synchrony. We study the response of a bursting pallidal neuron to different patterns of synaptic input from subthalamic nucleus (STN) neuron. We show how external globus pallidus (GPe) neuron is sensitive to the phase of the input from the STN cell and can exhibit intermittent phase-locking with the input in the beta band. The temporal properties of this intermittent phase-locking show similarities to the intermittent synchronization observed in experiments. We also study the synchronization of GPe cells to synaptic input from the STN cell with dependence on the dopamine-modulated parameters. Earlier studies showed how the strengthening of dopamine-modulated coupling may lead to transitions from non-synchronized to partially synchronized dynamics, typical in Parkinson's disease. However, dopamine also affects the cellular properties of neurons. We show how the changes in firing patterns of STN neuron due to the lack of dopamine may lead to transition from a lower to a higher coherent state, roughly matching the synchrony levels observed in basal ganglia in normal and parkinsonian states. The intermittent nature of the neural beta band synchrony in Parkinson's disease is achieved in the model due to the interplay of the timing of STN input to pallidum and pallidal neuronal dynamics, resulting in sensitivity of pallidal output to the phase of the arriving STN input. Thus the mechanism considered here (the change in firing pattern of subthalamic neurons through the dopamine-induced change of membrane properties) may be one of the potential mechanisms responsible for the generation of the intermittent synchronization observed in Parkinson's disease.

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Examples of the GPe response (gray line) to rhythmic synaptic inputs driven by STN activity (black line) when  = 0.5. A) and B) use periodic inputs generated by model STN neuron. C) uses a spike train from STN of a Parkinsonian patient recorded during surgical procedure. A) presents periodic (entrained) response when input period T = 60 ms and B) presents an irregular response when input period T = 85 ms.
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pone-0051530-g002: Examples of the GPe response (gray line) to rhythmic synaptic inputs driven by STN activity (black line) when  = 0.5. A) and B) use periodic inputs generated by model STN neuron. C) uses a spike train from STN of a Parkinsonian patient recorded during surgical procedure. A) presents periodic (entrained) response when input period T = 60 ms and B) presents an irregular response when input period T = 85 ms.

Mentions: A rhythmic response of GPe cell to the periodic STN activity is shown in Figure 2A. The number of spikes within a GPe cell burst alternates between 4 and 5. The first burst in the figure illustrates an elongation of the GPe cell response due to the input from STN cell, which was given in the middle of GPe cell's active phase. Additional firings are driven by STN input and the extended burst ends as the input terminates. On the other hand, the second burst in the same figure shows an initiation of GPe cell response by the STN input. In this case, although the input is terminated, GPe cell fires additional spike because the calcium level is still insufficiently high. In either case, the spikes within the burst are tightly phase-locked to those of the input.


Potential mechanisms for imperfect synchronization in parkinsonian basal ganglia.

Park C, Rubchinsky LL - PLoS ONE (2012)

Examples of the GPe response (gray line) to rhythmic synaptic inputs driven by STN activity (black line) when  = 0.5. A) and B) use periodic inputs generated by model STN neuron. C) uses a spike train from STN of a Parkinsonian patient recorded during surgical procedure. A) presents periodic (entrained) response when input period T = 60 ms and B) presents an irregular response when input period T = 85 ms.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3526636&req=5

pone-0051530-g002: Examples of the GPe response (gray line) to rhythmic synaptic inputs driven by STN activity (black line) when  = 0.5. A) and B) use periodic inputs generated by model STN neuron. C) uses a spike train from STN of a Parkinsonian patient recorded during surgical procedure. A) presents periodic (entrained) response when input period T = 60 ms and B) presents an irregular response when input period T = 85 ms.
Mentions: A rhythmic response of GPe cell to the periodic STN activity is shown in Figure 2A. The number of spikes within a GPe cell burst alternates between 4 and 5. The first burst in the figure illustrates an elongation of the GPe cell response due to the input from STN cell, which was given in the middle of GPe cell's active phase. Additional firings are driven by STN input and the extended burst ends as the input terminates. On the other hand, the second burst in the same figure shows an initiation of GPe cell response by the STN input. In this case, although the input is terminated, GPe cell fires additional spike because the calcium level is still insufficiently high. In either case, the spikes within the burst are tightly phase-locked to those of the input.

Bottom Line: However, dopamine also affects the cellular properties of neurons.The intermittent nature of the neural beta band synchrony in Parkinson's disease is achieved in the model due to the interplay of the timing of STN input to pallidum and pallidal neuronal dynamics, resulting in sensitivity of pallidal output to the phase of the arriving STN input.Thus the mechanism considered here (the change in firing pattern of subthalamic neurons through the dopamine-induced change of membrane properties) may be one of the potential mechanisms responsible for the generation of the intermittent synchronization observed in Parkinson's disease.

View Article: PubMed Central - PubMed

Affiliation: Department of Mathematical Sciences and Center for Mathematical Biosciences, Indiana University Purdue University Indianapolis, Indianapolis, IN, USA. 21cspark@gmail.com

ABSTRACT
Neural activity in the brain of parkinsonian patients is characterized by the intermittently synchronized oscillatory dynamics. This imperfect synchronization, observed in the beta frequency band, is believed to be related to the hypokinetic motor symptoms of the disorder. Our study explores potential mechanisms behind this intermittent synchrony. We study the response of a bursting pallidal neuron to different patterns of synaptic input from subthalamic nucleus (STN) neuron. We show how external globus pallidus (GPe) neuron is sensitive to the phase of the input from the STN cell and can exhibit intermittent phase-locking with the input in the beta band. The temporal properties of this intermittent phase-locking show similarities to the intermittent synchronization observed in experiments. We also study the synchronization of GPe cells to synaptic input from the STN cell with dependence on the dopamine-modulated parameters. Earlier studies showed how the strengthening of dopamine-modulated coupling may lead to transitions from non-synchronized to partially synchronized dynamics, typical in Parkinson's disease. However, dopamine also affects the cellular properties of neurons. We show how the changes in firing patterns of STN neuron due to the lack of dopamine may lead to transition from a lower to a higher coherent state, roughly matching the synchrony levels observed in basal ganglia in normal and parkinsonian states. The intermittent nature of the neural beta band synchrony in Parkinson's disease is achieved in the model due to the interplay of the timing of STN input to pallidum and pallidal neuronal dynamics, resulting in sensitivity of pallidal output to the phase of the arriving STN input. Thus the mechanism considered here (the change in firing pattern of subthalamic neurons through the dopamine-induced change of membrane properties) may be one of the potential mechanisms responsible for the generation of the intermittent synchronization observed in Parkinson's disease.

Show MeSH
Related in: MedlinePlus