Explaining pathological changes in axonal excitability through dynamical analysis of conductance-based models.
Explaining pathological changes in axonal excitability through dynamical analysis of conductance-based models.
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DOI：
10.1088/1741-2560/8/6/065002
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发表时间：
2011-12
影响因子：
4
通讯作者：
Prescott SA
中科院分区：
文献类型：
--
作者：
Coggan JS;Ocker GK;Sejnowski TJ;Prescott SA
Neurons rely on action potentials, or spikes, to relay information. Pathological changes in spike generation likely contribute to certain enigmatic features of neurological disease, like paroxysmal attacks of pain and muscle spasm. Paroxysmal symptoms are characterized by abrupt onset and short duration, and are associated with abnormal spiking although the exact pathophysiology remains unclear. To help decipher the biophysical basis for ‘paroxysmal’ spiking, we replicated afterdischarge (i.e. continued spiking after a brief stimulus) in a minimal conductance-based axon model. We then applied nonlinear dynamical analysis to explain the dynamical basis for initiation and termination of afterdischarge. A perturbation could abruptly switch the system between two (quasi-)stable attractor states: rest and repetitive spiking. This bistability was a consequence of slow positive feedback mediated by persistent inward current. Initiation of afterdischarge was explained by activation of the persistent inward current forcing the system to cross a saddle point that separates the basins of attraction associated with each attractor. Termination of afterdischarge was explained by the attractor associated with repetitive spiking being destroyed. This occurred when ultra-slow negative feedback, such as intracellular sodium accumulation, caused the saddle point and stable limit cycle to collide; in that regard, the active attractor is not truly stable when the slowest dynamics are taken into account. The model also explains other features of paroxysmal symptoms, including temporal summation and refractoriness.
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DOI：
10.1073/pnas.1013798107
发表时间：
2010-11-30
影响因子：
11.1
作者：
Coggan, Jay S.;Prescott, Steven A.;Sejnowski, Terrence J.
通讯作者：
Sejnowski, Terrence J.
影响因子：
13.9
作者：
Costigan M;Scholz J;Woolf CJ
通讯作者：
Woolf CJ
影响因子：
5.5
作者：
BOSTOCK, H;BAKER, M;REID, G
通讯作者：
REID, G
影响因子：
14.5
作者：
OCHOA, JL;TOREBJORK, HE
通讯作者：
TOREBJORK, HE
影响因子：
11
作者：
TWOMEY, JA;ESPIR, MLE
通讯作者：
ESPIR, MLE