Associative Conditioning Is a Robust Systemic Behavior in Unicellular Organisms: An Interspecies Comparison

Abstract

The capacity to learn new efficient systemic behavior is a fundamental issue of contemporary biology. We have recently observed, in a preliminary analysis, the emergence of conditioned behavior in some individual amoebae cells. In these experiments, cells were able to acquire new migratory patterns and remember them for long periods of their cellular cycle, forgetting them later on. Here, following a similar conceptual framework of Pavlov’s experiments, we have exhaustively studied the migration trajectories of more than 2000 individual cells belonging to three different species: Amoeba proteus, Metamoeba leningradensis, and Amoeba borokensis. Fundamentally, we have analyzed several relevant properties of conditioned cells, such as the intensity of the responses, the directionality persistence, the total distance traveled, the directionality ratio, the average speed, and the persistence times. We have observed that cells belonging to these three species can modify the systemic response to a specific stimulus by associative conditioning. Our main analysis shows that such new behavior is very robust and presents a similar structure of migration patterns in the three species, which was characterized by the presence of conditioning for long periods, remarkable straightness in their trajectories and strong directional persistence. Our experimental and quantitative results, compared with other studies on complex cellular responses in bacteria, protozoa, fungus-like organisms and metazoans that we discus here, allow us to conclude that cellular associative conditioning might be a widespread characteristic of unicellular organisms. This new systemic behavior could be essential to understand some key principles involved in increasing the cellular adaptive fitness to microenvironments.

Forces directing the systemic correlations of cell migration

“…On the other hand, long-term correlations have also been showed in different metabolic processes such as calcium-activated potassium channels (84), intracellular transport pathway of Chlamydomonas (85), glycolytic studies (86)(87)(88)(89), NADPH series (90), and metabolic networks (91,92), attractor dynamics (93), neural activity (94). In additions, complex emergent systemic behaviors have been observed in cellular locomotion movements (95,96).…”

Behavioral plasticity in aneural organisms.

“…Experiments with three species of amoebae show that pairing of a weak electric field that generates movement toward the cathode (the CS) with a peptide secreted by bacteria, the amoeba’s prey, located in the anode side (the US) generates a change in the direction of movement (Carrasco-Pujante et al, 2021). In the absence of either the CS or US, individual amoebae move in all directions from the location where they are placed.…”

Many Paths to Anticipatory Behavior: Anticipatory Model Acquisition Across Phylogenetic and Ontogenetic Timescales

“…As such, I will refrain from rehearsing any particular example(s) here and refer the interested reader to Ginsburg and Jablonka (2019). That said, it is interesting to note that as of today, examples of associative-like learning in non-neuronal organisms are rare and limited to a few studies on paramecia (Gelber 1952(Gelber , 1958Armus et al 2006), amoebae (De la Fuente et al 2019Carrasco-Pujante et al 2021), and a possible example in pea plants (Gagliano et al 2016). This might be taken to suggest that anticipatory learning-based model acquisition is largely restricted to neuronal organisms.…”

“…In doing so, this article helps shed light on how AB might arise in the wide range of organisms that it has been observed in, something that is important under the assumption that not every form of model acquisition is found across all taxa. Associative learning-based acquisition, for example, might go a long way in explaining how many cases of AB arise in many animals (Ginsburg and Jablonka 2019) and plants (Gagliano et al 2016; but see Markel 2020) and amoebae (De la Fuente et al 2019;Carrasco-Pujante et al 2021); however, it fails to account for AB in bacteria, yeast, or slime mold, organisms for which there is currently a lack of substantiated evidence supporting the presence of associative learning. Something else in these organisms must account for their AB.…”