Optimization of input parameters to a CN neuron model to simulate its activity during and between epileptic absence seizures
© Alva et al. 2015
Published: 4 December 2015
We then used a morphologically realistic conductance-based model of an excitatory CN projection neuron  to simulate the interictal activity of a participating CN neuron. We selected a cluster where all neurons participated in the seizures, indicated by black crosses (+) in Fig. 1, and applied an Evolutionary algorithm (EA) to optimize excitatory and inhibitory input parameters to the CN neuron model such as spike rates, noise, burst parameters, synchronicity, synaptic weights so that the output data point of the EA moved closer to the centre of the selected cluster. The results of the EA indicated that the CN neurons that participated in absence seizures received either a synchronous, bursting inhibitory input or a synchronous, bursting excitatory input. Next, we modified the EA such that the initial input parameters of the CN neuron model resulted in an output data point nearest to the center of the selected interictal cluster, and ran the optimization to move the output data point to the center of the cluster that was formed from the ictal counter-parts of the CN neurons of the selected participating cluster. Surprisingly, a very small change in input parameters could result in a shift from the interictal to the ictal cluster centre and result in a transition to CN neuron activity as observed during seizures. However, when we blocked the Purkinje cell input to the CN neuron model by maintaining the inhibitory synaptic weight at zero, the output data point never reached the center of the ictal cluster. This suggests that blocking Purkinje cell input to the CN neuron can prevent the CN neuron from participating in the absence seizure.
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