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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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Geometric analysis of GPe cell.A) Bifurcation diagram of the GPe cell with [Ca] as bifurcation parameter. This is an elliptic burster. B) Projection of a bursting solution onto this diagram. C) An example of delayed bifurcation. D) [Ca] value when it jumps up as a function of [Ca] when it jumps down (gray). Black line is a linear fitting of this function.
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pone-0051530-g004: Geometric analysis of GPe cell.A) Bifurcation diagram of the GPe cell with [Ca] as bifurcation parameter. This is an elliptic burster. B) Projection of a bursting solution onto this diagram. C) An example of delayed bifurcation. D) [Ca] value when it jumps up as a function of [Ca] when it jumps down (gray). Black line is a linear fitting of this function.

Mentions: In [15], we found that the parameter region for the experimentally observed intermittent synchrony resides in the large boundary between synchronized and nonsynchronized dynamics. Over this boundary region, ranges from 4 to 10 (Figure 4 in that paper). In the current study, is fixed at 7 as one representative value within that range of . As increases, inter-burst interval decreases slightly and number of spikes per burst eventually increases by 1 when is 8. However, the results under different values are qualitatively the same, For , the model GPe model fires bursts with 3 spikes where two inter-burst intervals, 51.15 ms (std. 0.0549) and 40.92 ms (std. 0.0536), alternate (Fig. 1A). As explained in Methods section, the activity of the STN cell was delivered to the GPe cell through synaptic variables to give a better approximation than using a pulse-like input. Due to the non-instantaneous nature of synaptic variable, it takes some time for firings of the STN cell to affect the GPe cell. The strength of the STN to GPe synapse  = 0.5. This is a relatively strong synaptic strength, so that the GPe cell responds faithfully to synaptic inputs in most cases.


Potential mechanisms for imperfect synchronization in parkinsonian basal ganglia.

Park C, Rubchinsky LL - PLoS ONE (2012)

Geometric analysis of GPe cell.A) Bifurcation diagram of the GPe cell with [Ca] as bifurcation parameter. This is an elliptic burster. B) Projection of a bursting solution onto this diagram. C) An example of delayed bifurcation. D) [Ca] value when it jumps up as a function of [Ca] when it jumps down (gray). Black line is a linear fitting of this function.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0051530-g004: Geometric analysis of GPe cell.A) Bifurcation diagram of the GPe cell with [Ca] as bifurcation parameter. This is an elliptic burster. B) Projection of a bursting solution onto this diagram. C) An example of delayed bifurcation. D) [Ca] value when it jumps up as a function of [Ca] when it jumps down (gray). Black line is a linear fitting of this function.
Mentions: In [15], we found that the parameter region for the experimentally observed intermittent synchrony resides in the large boundary between synchronized and nonsynchronized dynamics. Over this boundary region, ranges from 4 to 10 (Figure 4 in that paper). In the current study, is fixed at 7 as one representative value within that range of . As increases, inter-burst interval decreases slightly and number of spikes per burst eventually increases by 1 when is 8. However, the results under different values are qualitatively the same, For , the model GPe model fires bursts with 3 spikes where two inter-burst intervals, 51.15 ms (std. 0.0549) and 40.92 ms (std. 0.0536), alternate (Fig. 1A). As explained in Methods section, the activity of the STN cell was delivered to the GPe cell through synaptic variables to give a better approximation than using a pulse-like input. Due to the non-instantaneous nature of synaptic variable, it takes some time for firings of the STN cell to affect the GPe cell. The strength of the STN to GPe synapse  = 0.5. This is a relatively strong synaptic strength, so that the GPe cell responds faithfully to synaptic inputs in most cases.

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