Quantitative Neurobiology of Hydra

To understand the origins of disease, we must explore host physiology as a metaorganism—a dynamic system shaped by the interaction and coevolution of host biology, microbes, and the environment. Specifically, my goal is to understand how molecular factors and microbiota influence the homeostasis of neuronal networks and related behaviors in Hydra.

Central to this is decoding the neural code—mapping the neural substrates that drive behavior. In my team, we focus on the small cnidarian Hydra vulgaris, which has a primitive and relatively simple nervous system that could potentially be fully understood. The nervous system consists of 200-2,000 neurons (depending on the size of the animal) that belong to only eleven cell types, organized into two nerve nets without cephalization or ganglia. Hydra exhibits a well-characterized behavioral repertoire, which has been categorized and quantified using machine learning techniques. This repertoire includes simple movements like contractions, twists, and elongations, as well as more complex fixed-action patterns, such as feeding, locomotion through somersaulting and inch-worming, and even some learning paradigms [6]. As a polyp, the Hydra possesses remarkable regenerative capabilities, making it an ideal subject for studying neurodevelopment and the impact of molecular or genetic perturbations on neural connectivity.

From an experimental standpoint, Hydra’s transparency and small size make it an ideal model for microscopy, with nearly all of its neurons suitable for high-speed confocal imaging using calcium indicators. We developed a GCaMP-expressing Hydra colony, and calcium imaging is performed at the institute’s imaging platform.

Although primitive, the molecular toolkit and functional organization of the Hydra nervous system mirror those of more evolved bilaterian organisms. In particular, Hydra’s nerve net activity is organized into coactive neuronal ensembles that can be considered as functional units, similar to the mammalian cerebral cortex. They represent fundamental building blocks, or the “alphabet” of the neural code. The main neuronal ensembles in Hydra are rhythmically activated, providing a useful model for studying central pattern generators and their modulation by neuropeptides and the animal microbiome. This rhythmic activity is particularly relevant in the context of human physiology, as recent studies have shown that disturbances in the gut microbiota can disrupt pacemaker rhythmicity and gut motility, leading to gastrointestinal conditions like irritable bowel syndrome.

To develop a comprehensive framework that would link neuronal activity to behavior, we focus on three main research axis:

1. Robust, long-term monitoring of single-neuron activity in behaving Hydra
2. Development of a statistical framework to relate single-neuron activity to the neural substrates underlying behavior.
3. Creation of an integrated mathematical model and simulation tools that combine imaging and behavioral data to explore how environmental factors (such as light, salinity, etc.) and molecular factors, such as neuropeptides, modulate the functional organization of Hydra’s neural network and behavior.

This approach will not only deepen our understanding of Hydra’s neural function but also contribute to the broader field of integrating and elucidating the influence of various factors on neural development and homeostasis.