Memory in the enteric nervous system

Project summary The formation of memories is central to the human condition. It enables learning and the accumulation of knowledge over the lifespan, and it allows using the past in order to inform the future. While the mechanisms underlying the neural basis of memory have been extensively studied in the brain, whether memory exists in the peripheral nervous system, and in particular the enteric nervous system (ENS), remains unknown, representing a fundamental gap in our knowledge of peripheral neuroscience and gastrointestinal physiology. The goal of this study is to address this fundamental question. Our proposal is based on exciting preliminary evidence for the existence of memory in the ENS. We have observed the formation of enteric neural engrams in response to gastrointestinal stimuli and have characterized the molecular, temporal, and functional characteristics of these engrams. We now aim to build the tools required for studying the formation and meaning of ENS memories. We will then use these tools in combination with microbial, xenobiotic, and dietary perturbations in animal models, in order to transform our understanding of numerous functions and diseases of the gastrointestinal tract through the lens of enteric neural engrams. This project will impact the study of gastrointestinal and metabolic diseases in three major ways: First, it will uncover a fundamentally new aspect of ENS biology. Memory formation in the brain has been studied for decades, and its proper function is critical for organismal survival. Understanding the memory capacity of the ENS would enable us to add several new layers to the canonical functions of enteric neurons. Second, our study will provide new insights into the nature of memory. Memory formation is generally studied in response to sensory information (neuroscience) or antigen exposure (immunology). Our investigations will extend this concept, by highlighting biotic and abiotic gastrointestinal triggers of memory formation. Third, our study may provide the conceptual framework for an entirely new approach to treating diseases associated with the gastrointestinal tract – one that focuses on information stored in enteric neurons.