Histamine Regulates Mucus Rheology and Determines Mode of Locomotion in Planarians

Freshwater planarians are a prominent model for studying regeneration and stem cell dynamics. In particular, they are an ideal system to study neuro-regeneration, because they are the most complex organism with the ability to regrow a fully functional CNS, they possess most of the different types of neurons found in higher organisms (serotoninergic, GABAnergic, dopaminergic, histaminergic, etc), and they show sufficiently complex behaviors that can be quantified. These features make planarians well-suited for studying the role of neurotransmitters in neurodegenerative diseases for which currently no cure exists and for which stem cell based therapy is the hope of the future. One neurotransmitter which has been relatively little studied but was recently shown to be altered in patients' brains in both Alzheimer's and Parkinson's diseases, is histamine. Histamine is known to be involved in a number of biological processes, spanning from its well-documented function in allergic reactions, gastric secretion and inflammation to higher cognitive functions such as arousal, nociception and sleep regulation. In my talk I will discuss the regulatory role of the histamine signaling pathway for planarian locomotion by changing mucus composition. By using mechanical, molecular, and pharmacological perturbations we modify mucus properties and thus control planarian behavior. We determined a novel form of locomotion which is characterized by periodic elongations and contractions of the animal’s body and which can be captured by a simple mechanical model. We show that this behavior is under control of the histaminergic system and due to its striking phenotype makes an ideal candidate for studying the role of histamine signaling on nervous system function in the context of homeostasis, injury, and regeneration.