Clusters of cooperative ion channels enable a membrane-potential-based mechanism for short-term memory

Across biological systems, cooperativity between proteins enables fast actions, supra-linear responses, and long-lasting molecular switches. In the nervous system, however, the function of cooperative interactions between voltage-dependent ionic channels remains largely unknown. Based on mathematical modeling, we here demonstrate that clusters of strongly cooperative ion channels can plausibly form bistable conductances. Consequently, clusters are permanently switched on by neuronal spiking, switched off by strong hyperpolarization, and remain in their state for seconds after stimulation. The resulting short-term memory of the membrane potential allows to generate persistent firing when clusters of cooperative channels are present together with non-cooperative spike-generating conductances. Dynamic clamp experiments in rodent cortical neurons confirm that channel cooperativity can robustly induce graded persistent activity - a single-cell based, multistable mnemonic firing mode experimentally observed in several brain regions. We therefore propose that ion channel cooperativity constitutes an efficient cell-intrinsic implementation for short-term memories at the voltage level.