BPS2026 – A receptor inactivation model for habituation in the single cell Stentor coeruleus

Learning and memory are often considered unique attributes of animals with a nervous system, but even single cells are capable of simple learning. Stentor coeruleus is a single-celled organism that contracts in response to mechanical pulses but habituates to these pulses after repeated trials. Habituation is a type of learning in which a response gradually declines after repeated stimulation, but the mechanism of learning in a single cell that lacks a nervous system is currently unknown. Here, we propose a model of habituation based on properties of receptor molecules and prior electrophysiological experiments in Stentor. In this biochemistry-based habituation model, Stentor mechanoreceptors sense stimuli and open ion channels, thus changing the membrane potential and eventually triggering an action potential that drives contraction. Over the course of habituation, activated mechanoreceptors can become inactivated or internalized and subsequently degraded or recycled, resulting in a loss of the contractile response to mechanical stimulation. Simulations confirmed that this model recapitulates key empirical features of Stentor habituation, such as the step-like responses of individual cells, and the dependence of habituation rate on stimulus magnitude and frequency. Additionally, the model predicts that delivering strong stimuli, which typically do not result in habituation, should drive habituation to weaker stimuli because the receptor numbers, functioning as an internal hidden variable, are decreasing. New habituation experiments that alternated between weak and strong stimuli confirmed this model prediction. The model also predicts subliminal accumulation, a phenomenon in which continuation of training even after cells reach asymptotic levels of habituation improves memory retention, and we confirmed this prediction with new experiments. Taken together, these model simulations and new experiments shed light on the mechanisms of learning in a single cell independent of a complex nervous system.