Alternative neural systems: What is a neuron? (Ctenophores, sponges and placozoans)

How to make a neuron, a synapse, and a neural circuit? Is there only one 'design' for a neural architecture with a universally shared genomic blueprint across species? The brief answer is "No." Four early divergent lineages from the nerveless common ancestor of all animals independently evolved distinct neuroid-type integrative systems. One of these is a subset of neural nets in comb jellies with unique synapses; the second lineage is the well-known Cnidaria + Bilateria; the two others are non-synaptic neuroid systems in sponges and placozoans. By integrating scRNA-seq and microscopy data, we revise the definition of neurons as synaptically-coupled polarized and highly heterogenous secretory cells at the top of behavioral hierarchies with learning capabilities. This physiological (not phylogenetic) definition separates 'true' neurons from non-synaptically and gap junction-coupled integrative systems executing more stereotyped behaviors. Growing evidence supports the hypothesis of multiple origins of neurons and synapses. Thus, many non-bilaterian and bilaterian neuronal classes, circuits or systems are considered functional rather than genetic categories, composed of non-homologous cell types. In summary, little-explored examples of convergent neuronal evolution in representatives of early branching metazoans provide conceptually novel microanatomical and physiological architectures of behavioral controls in animals with prospects of neuro-engineering and synthetic biology.