Programming Molecular Systems To Emulate a Learning Spiking Neuron

[Image: see text] Hebbian theory seeks to explain how the neurons in the brain adapt to stimuli to enable learning. An interesting feature of Hebbian learning is that it is an unsupervised method and, as such, does not require feedback, making it suitable in contexts where systems have to learn autonomously. This paper explores how molecular systems can be designed to show such protointelligent behaviors and proposes the first chemical reaction network (CRN) that can exhibit autonomous Hebbian learning across arbitrarily many input channels. The system emulates a spiking neuron, and we demonstrate that it can learn statistical biases of incoming inputs. The basic CRN is a minimal, thermodynamically plausible set of microreversible chemical equations that can be analyzed with respect to their energy requirements. However, to explore how such chemical systems might be engineered de novo, we also propose an extended version based on enzyme-driven compartmentalized reactions. Finally, we show how a purely DNA system, built upon the paradigm of DNA strand displacement, can realize neuronal dynamics. Our analysis provides a compelling blueprint for exploring autonomous learning in biological settings, bringing us closer to realizing real synthetic biological intelligence.