Hierarchical Modularity in the Reassembly of Hydra’s Nervous System

Modularity plays a pivotal role in evolution, as the compartmentalization of components of a system allows their independent optimization in isolation, minimizing the effect on the system as a whole. As a manifestation of this universal design principle, evidence suggests modularity plays a key role in the function of the brain as well, allowing the compartmentalization of specific structural and functional units before their integration. Despite this, it’s unknown how modularity arises during the development of neural circuits. Accordingly, observing the development of the modularity of the nervous system and correlating this with the emergence of specific behaviors has the potential to highlight features of the functional role of modularity in the mature nervous system. To explore this issue, we work with the small cnidarian Hydra vulgaris, a representative of some of the simplest nervous systems in evolution. Depending on the size of the animal, Hydra’s isometrically scaling nervous system of 300-2,000 neurons is organized in two independent nerve nets in its ectoderm and endoderm and is distributed through the body of the animal without any cephalization or ganglia. Moreover, under the right conditions Hydra can reassemble itself into a normal animal after complete dissociation into individual cells. Using transgenic Hydra which express the calcium sensor GCaMP6s in every neuron (Dupre and Yuste, 2017) we have imaged the neuronal activity of dissociated preparations as they re-aggregate then regenerate over a period of several days. We demonstrate the robust synchronization of Hydra’s neural nets during the process. Of the possible routes toward synchronization, we observe that an initially random structure takes on a hierarchical organization as small groups of neurons synchronize. As these proto-circuits further synchronize, the modularity of the system increases, accompanied by a loss of the hierarchical depth of the network structure as normal behavioral rhythms resume during regeneration.