A new look at the architecture and dynamics of the Hydra nerve net The Hydra nervous system is a paradigm of a 'simple nerve net'. Nerve cells in Hydra, like many cnidarian polyps, are organized in a nerve net extending throughout the body column. This nerve net is essential for controlling spontaneous behavior: elimination of nerve cells leads to polyps that do not move and are incapable of capturing and ingesting prey (Campbell, 1976). We have re-examined the structure of the Hydra nerve net using a novel antibody that stains all nerve cells in Hydra. Confocal imaging shows that there are two distinct nerve nets, one in the ectoderm and one in the endoderm, with the unexpected absence of nerve cells in the endoderm of the tentacles. The nerve nets in the ectoderm and endoderm do not contact each other. High-resolution TEM and serial block face SEM show that the nerve nets consist of bundles of parallel overlapping neurites. Results from transgenic lines show that neurite bundles include different neural circuits and hence that neurites in bundles require circuit-specific recognition. Nerve cell-specific innexins indicate that gap junctions can provide this specificity. The occurrence of bundles of neurites supports a model for continuous growth and differentiation of the nerve net by lateral addition of new nerve cells to the existing net. This model was confirmed by tracking newly differentiated nerve cells. This work presents important findings on the cellular and ultrastructural organization of the nervous system in the freshwater polyp Hydra. The authors present outstanding imaging data with convincing evidence to support their claims. The manuscript provides a starting point for further functional in vivo studies. The work will be of interest to developmental biologists and neurobiologists. Nerve cells arose early in the evolution of multicellular animals to sense the environment and control the activity of downstream effector cells. In non-bilaterians (cnidarians and ctenophores) nerve cells are organized in nerve nets, which are often associated with muscle processes and coordinate the behaviors that involve ectodermal and endodermal tissues. In bilaterian metazoans, the number of nerve cells is commonly much higher than in cnidarians and ctenophores and – importantly – nerves are organized into a centralized nervous system with large ganglia. The relatively simple organization of nervous tissue in non-bilaterians offers the possibility of achieving a comprehensive understanding of the relationship between the architecture and activity of the nervous system and animal behavior. With a nervous system consisting of only 500–2000 nerve cells, depending on animal size, the freshwater cnidarian polyp Hydra is a particularly useful model organism for such investigations. Furthermore, there are only two types of nerve cells in Hydra based on morphology: ganglion cells and sensory cells, and there are no surrounding support cells, such as glial cells in bilaterians. Ganglion cells are bipolar or multipolar,A new look at the architecture and dynamics of the Hydra nerve net The Hydra nervous system is a paradigm of a 'simple nerve net'. Nerve cells in Hydra, like many cnidarian polyps, are organized in a nerve net extending throughout the body column. This nerve net is essential for controlling spontaneous behavior: elimination of nerve cells leads to polyps that do not move and are incapable of capturing and ingesting prey (Campbell, 1976). We have re-examined the structure of the Hydra nerve net using a novel antibody that stains all nerve cells in Hydra. Confocal imaging shows that there are two distinct nerve nets, one in the ectoderm and one in the endoderm, with the unexpected absence of nerve cells in the endoderm of the tentacles. The nerve nets in the ectoderm and endoderm do not contact each other. High-resolution TEM and serial block face SEM show that the nerve nets consist of bundles of parallel overlapping neurites. Results from transgenic lines show that neurite bundles include different neural circuits and hence that neurites in bundles require circuit-specific recognition. Nerve cell-specific innexins indicate that gap junctions can provide this specificity. The occurrence of bundles of neurites supports a model for continuous growth and differentiation of the nerve net by lateral addition of new nerve cells to the existing net. This model was confirmed by tracking newly differentiated nerve cells. This work presents important findings on the cellular and ultrastructural organization of the nervous system in the freshwater polyp Hydra. The authors present outstanding imaging data with convincing evidence to support their claims. The manuscript provides a starting point for further functional in vivo studies. The work will be of interest to developmental biologists and neurobiologists. Nerve cells arose early in the evolution of multicellular animals to sense the environment and control the activity of downstream effector cells. In non-bilaterians (cnidarians and ctenophores) nerve cells are organized in nerve nets, which are often associated with muscle processes and coordinate the behaviors that involve ectodermal and endodermal tissues. In bilaterian metazoans, the number of nerve cells is commonly much higher than in cnidarians and ctenophores and – importantly – nerves are organized into a centralized nervous system with large ganglia. The relatively simple organization of nervous tissue in non-bilaterians offers the possibility of achieving a comprehensive understanding of the relationship between the architecture and activity of the nervous system and animal behavior. With a nervous system consisting of only 500–2000 nerve cells, depending on animal size, the freshwater cnidarian polyp Hydra is a particularly useful model organism for such investigations. Furthermore, there are only two types of nerve cells in Hydra based on morphology: ganglion cells and sensory cells, and there are no surrounding support cells, such as glial cells in bilaterians. Ganglion cells are bipolar or multipolar,