A receptor-inactivation model for single-celled habituation in Stentor coeruleus

Deepa H Rajan; Wallace F Marshall

doi:10.1016/j.cub.2025.05.071

A receptor-inactivation model for single-celled habituation in Stentor coeruleus

Curr Biol. 2025 Jun 20:S0960-9822(25)00687-6. doi: 10.1016/j.cub.2025.05.071. Online ahead of print.

Authors

Deepa H Rajan¹, Wallace F Marshall²

Affiliations

¹ Department of Biochemistry and Biophysics, University of California, San Francisco, 600 16th Street, San Francisco, CA 94158, USA.
² Department of Biochemistry and Biophysics, University of California, San Francisco, 600 16th Street, San Francisco, CA 94158, USA. Electronic address: wallace.marshall@ucsf.edu.

PMID: 40562036
DOI: 10.1016/j.cub.2025.05.071

Abstract

The single-celled ciliate Stentor coeruleus demonstrates habituation to mechanical stimuli, but the mechanism of learning in this single cell, which lacks a nervous system, is currently not known. Here, we propose a simple biochemistry-based model based on prior electrophysiological measurements in Stentor along with general properties of receptor molecules. In this model, a mechanoreceptor senses the stimulus, which leads to channel opening to change membrane potential, with a sufficient change in polarization triggering an action potential that drives contraction. Receptors that are activated can become internalized, after which they can either be degraded or recycled back to the cell surface. Simulations of this model confirm that it is capable of showing habituation similar to what is seen in actual Stentor cells, including the apparently step-like response of individual cells during habituation. The model also can account for additional habituation hallmarks, including the dependence of habituation rate on stimulus magnitude and the ability of high-frequency stimulus sequences to drive faster and more extensive habituation. The model makes the prediction that application of high-force stimuli that do not normally habituate should drive habituation to weaker stimuli due to a decrease in the receptor numbers, which serves as an internal hidden variable. We confirmed this prediction using two new sets of experiments involving the alternation of weak and strong stimuli. The model also predicts subliminal accumulation, wherein continuation of training, even after habituation has reached asymptotic levels, should lead to delayed response recovery, which was also confirmed by new experiments.

Keywords: basal cognition; dishabituation; frequency response; latent memory; low-pass filter; membrane potential; potentiation; rate sensitivity; receptor degradation; receptor endocytosis.