Uncommon and common roles of inhibitory interneuron and autapse and their cooperations to induce or eliminate epileptiform firing of pyramidal neuron.

Different from the common role of inhibitory modulations to suppress firing activities, uncommon roles of inhibitory modulations are observed in recent experiments. For instance, inhibitory autapse can enhance spiking frequency of interneuron, and inhibitory interneuron can enhance spiking of pyramidal neuron to epileptiform firing with high membrane potential and extracellular potassium concentration, presenting possible novel etiology of brain diseases and challenge to excitation-inhibition balance. In the present paper, the uncommon roles, the common roles, and their cooperations are studied in a computation model. Firstly, the inhibitory interneuron with fast instead of slow decay synaptic current plays an uncommon role, and the complex process for the uncommon role is obtained. Compared with slow decay, the fast decay inhibitory synaptic current is strong enough to induce silence with low membrane potential, resulting in long silence and high level of extracellular potassium concentration when firing recovers, initiating positive feedback between firing and potassium concentration to induce the epileptiform firing. Secondly, inhibitory autaptic current with fast rather than slow decay plays an uncommon role to enhance spiking frequency of interneuron. Autaptic current with slow decay causes weak potassium current during downstroke of action potential to induce spike advanced. Finally, different cooperations between the common and uncommon roles of interneuron and autapse are obtained. Especially, fast autapse with great uncommon role can reverse the common role of interneuron, which can induce spiking to the epileptiform firing, and slow autapse with great common role can reverse the uncommon role of interneuron, which can change the epileptiform firing to spiking for the normal state. These findings present explanations to the uncommon roles of inhibitory modulations and multiple feasible measures to modulate the epileptiform firing and brain diseases.