Figure 5. Clusters of strongly cooperative ion channels mediate graded persistent activity in a simple neuron model.

(A) Repeated stimulation drives fast spiking in the neuron, which is followed by self-sustained, stable low-frequency activity at increasing rates (top). With each pulse, the driven, fast spiking switches more clusters to the open state and adds further stable conductances (bottom). The built-up conductance allows a persistent current to flow and sustains activity beyond stimulation. (B) In the same manner, strong hyperpolarization closes the clusters and allows to reduce the frequency of persistent activity until finally the cells stops firing. The simulation procedure is described in Materials and methods and parameters are summarized in Table 1.

Figure 5—figure supplement 1. Memory dynamics with different properties of cooperative channels.

The channel’s time constant and their conductance change the memory dynamics of the neuron probed with the multi-pulse protocol for graded persistent activity. (A) Variation of the time constant: When channels are fast (left, τ = 10 ms), the neuron is already maximally active after the first pulse - a few spikes suffice to open all clusters and there is only one level of persistent activity. Slower channels allow for a graded opening of channels and intermediate levels of persistent activity (middle, τ = 120 ms). If the channels are too slow and too few clusters open during the first pulse, the neuron remains silent (right, τ = 240 ms). (B) Frequency of persistent activity after each pulse for different time constants. (C) Variation of the channel conductance: When channels are low conducting, the persistent current remains subthreshold and is thus insufficient to drive persistent activity (left). At an intermediate conductance, the clusters mediate low frequency persistent activity (middle). When the provided conductance is too large, the high frequency persistent activity can open further clusters and is no longer stable. (D) Frequency of persistent activity after each pulse for different channel conductances. Other cluster parameters are summarized in Table 1.