PT - JOURNAL ARTICLE AU - Ildefonso M. De la Fuente AU - Carlos Bringas AU - Iker Malaina AU - María Fedetz AU - Alberto Pérez-Samartín AU - José I. López AU - Gorka Pérez-Yarza AU - María Dolores Boyano TI - Evidences of conditioned behavior in <em>Amoeba Proteus</em> AID - 10.1101/264176 DP - 2018 Jan 01 TA - bioRxiv PG - 264176 4099 - http://biorxiv.org/content/early/2018/02/12/264176.short 4100 - http://biorxiv.org/content/early/2018/02/12/264176.full AB - Associative memory is the main type of learning wherein complex organisms endowed with evolved nervous systems respond efficiently to determined environmental stimuli. This fundamental cognitive property has been evidenced in different multicellular species, from cephalopods to Humans, but never in individual cells. Here, following Pavlov’s experiments with dogs that founded the principles of classical conditioning, we have observed the development of an associative memory in Amoeba proteus, which corresponds to the emergence of a new systemic motility pattern. In our cellular version of this conditioning behavior, we have used a controlled direct current electric field as the conditioned stimulus and a specific chemotactic peptide as the non-conditioned stimulus. Our study allowed us to demonstrate that Amoeba proteus are capable of linking two independent past events, and the induced associative memory can be recorded for up to at least four hours. For the first time, it has been observed that a systemic response to a specific stimulus can be modified by learning in unicellular organisms. This finding opens up a new framework in the understanding of the mechanisms underlying the complex systemic behavior involved in the cellular migration and the adaptive capacity of cells to the external medium.