Evolutionary account of the soma location

The investigation of signal transmission in neurons with central and externalized soma was inspired by their distribution throughout the animal kingdom. In particular, neurons with central soma are commonly found in the central nervous system of mammals, while neurons with externalized soma are commonly found in the central nervous system of insects. This section summarizes the evolutionary development of unipolar and multipolar cells, which will be further discussed in Sec. 7.4. The overview begins with bipolar neurons, and then considers the derived morphologies of unipolar and multipolar cells more in detail, both on a cellular level, as well as in their network arrangement. The evolutionary perspective on the first project provides the framework within which I develop my arguments.

For simplicity, I will usehigherandloweranimals to denote species that are evolu-tionary later, respectively earlier derived, where the meaning oflaterandearliershould be understood in the context of the trait under consideration. In order to facilitate readability for the non-biologist, I also take the liberty to use the old-fashioned, but still common, terms of vertebrates and invertebrates. A more appropriate separation of the animal kingdom for the evolution of the soma location would be the use of super-phyla: Multipolar neurons are predominant in the central nervous system of all

1Ulfhake and Cullheim [169] refers to Peterset al.,Fine Structure of the Nervous System: Neurons and Their Supporting Cellsfrom 1976.

2.2. Evolutionary account of the soma location deuterostomiaincluding besides the vertebrates, for example, the closest cousins of the vertebrates, theechinodermata(sea urchin, starfish, sea cucumber, ...). Unipolar neurons, in contrast, are predominant in the central nervous system of most higherprotostomia, such ashexapoda(insects),crustaceaorcephalopoda. The soma location of various species can be found in the first publication, Supplemental Information.

Figure 2.2.:Neurons with externalized soma are common in insects, those with central soma in mammals.

2.2.1. Evolutionary origin

The evolutionary oldest morphology with dedicated axon and dendrite is probably the bipolar neuron. Most phyla with a nervous system evolved during the Cambrian explo-sion 570 to 530 million years ago [70]. Probably the first neurons were receptor cells that directly affected muscle tissue. The bipolar morphology lends itself to the transmission of signals from sensory receptors at the dendritic end, to a neuro-muscular junction at the axonal end. Indeed, the bipolar shape of motor neurons is much conserved over many phyla. In contrast to motor neurons, sensory neurons are commonly bipolar or unipolar². Yet, the bipolar shape is more common and probably the original shape of primary sensory cells [61]. Bipolar neurons are also abundant in the nervous system of lower invertebrates such asC. elegans, where a clear separation between periphery and central nervous system is often difficult. Together, these data suggest that the bipolar shape is one of the evolutionary oldest neuronal morphologies.

2.2.2. Complex signal processing

The development of interneurons, which relay information between sensory and motor neurons, allowed for more complex signal processing. The multipolar morphology with additional dendrites is a rather simple ramification of the bipolar shape, and probably evolutionary older than the unipolar morphology. Indeed, most lower invertebrates predominantly show multipolar neurons [157]. In more complex central nervous systems, such as those of insects or mammals, neurons have undergone a divergent

2Bipolar sensory neurons are common in invertebrates (exceptions are found,e.g., in the tentacles of theactinia(sea anemones) andpulmonata(snails and slugs)) [61], as well as in lower vertebrates such as fish and in the cochlear and vestibular ganglia of higher vertebrates such as mammals. Unipolar sensory neurons predominate in all other sensory ganglia of higher vertebrates [119].

Figure 2.3.:Hypothetical evolution of neuronal morphology from bipolar cells that directly link sensation and behavior, over simple interneurons (suitable for multi-sensory integration) to more complex unipolar and multipolar cells typical for the central nervous system of higher animals.

evolution of the soma location [154, 157]. Evolutionarily, the morphology with a central soma is probably the original, as suggested by the predominance of the multipolar shape inplatyhelminthes(flatworms) andechinodermata. A flatworm is probably similar to the ancestor of the vertebrates before invertebrates and vertebrates split³, and echinodermataare our closest cousins along the branch of thedeuterostomia, compare the first publication, Supplemental Information.

A continuous development away from multipolar cells to unipolar cells is suggested by the increasing proportion of neurons with externalized soma fromturbellariaover annelidaand somemolluscauntil in the central nervous system of arthropods nearly all neurons have an externalized soma [61]. Unipolar cells have developed several times during evolution. For example, dorsal root ganglion cells are bipolar in fish, but unipolar in birds and mammals [107], and hence clearly separate from the evolution of unipolar neurons in invertebrates⁴.

2.2.3. Centralization of the nervous system

In addition to a potential increase in complexity, the divergent evolution of unipolar and multipolar cells co-occurs with an increased centralization of the nervous system.

3Besides the multipolar shape, their neurons have dendritic spines, a single axon, and relatively little activity, while invertebrates show a tenfold higher spontaneous activity thanplanariaand vertebrates [139, 140].

4Neurons with externalized soma are, for example, also common in the optic tectum of fish [171].

2.2. Evolutionary account of the soma location Classically, the development of unipolar neurons in higher invertebrates is associated with centralization of their nervous system in ganglia. In ganglia, neuronal processes lie in the central neuropil, while the somata are located on the surface in a separate soma layer (the cortex layer), see Fig. 2.4. Not only the predominance of unipolar neurons, also the separation between central neuropil and cortex layer increase fromturbellaria overannelidaand somemollusca, and is, eventually, fully developed in arthropods [61].

Figure 2.4.:Neuronal arrangement. Top: In the rabbit (left), the nervous system is mostly organized in layered structures with somata and processes in direct proximity to each other (middle). The individual neurons are mostly multipolar (right). Bottom: In the locust (left), the nervous system is mostly organized in ganglia with the processes in a central neuropil, and the somata in a separate, superficial soma layer (middle). The individual neurons are mostly unipolar (right).

In contrast to the common claim that the separation between somata and neurites is related to the unipolar morphology, such a separation can also be observed in vertebrates with multipolar cells. The evolutionary oldest organization of the tectum in vertebrates is a laminar structure of alternating layers of somata and neuropil [33], and more examples can be found in Rivera-Alba et al. [133]. Furthermore, the separation of somata and neurites seems to have little consequence for function, as separated and non-separated somata and neurites can be observed in homologue structures:

Homologue brain regions in mammals andsauropsidacan show different histological organizations, the neocortex in mammals is for example layered, while the dorsal ventricular ridge insauropsidaformsnucleoids(ganglion-like structures) [33]. I take these observations as a hint that an explanation of unipolar and multipolar neurons is more likely to be found on the level of single neurons than on the level of the network arrangement, in line with the hypothesis from the first publication that soma location may optimize signal transmission in single cells.

2.2.4. Cellular similarities between unipolar and multipolar neurons

Besides their morphology, unipolar and multipolar neurons seem to be surprisingly similar. The cellular organization of neurons is, irrespective of their soma location, remarkably conserved throughout evolution. For example with regard to ion channels and signal transmission at chemical synapses, neurons function similarly across phyla [138]. It seems that evolution has not so much changed the cell biology of neurons, but rather their number and arrangement [154].

The cellular similarity between unipolar and multipolar neurons becomes particu-larly evident during neuronal development. Neurons of both morphologies go through similar phases, with the only apparent difference that the dendritic tree of unipolar neurons develops from the axon and not from the soma [135]. In fact, a small propor-tion of usually unipolar neurons from higher invertebrates naturally develop dendrites arising from the soma [87, 135]. On the other hand, dendrites growing off the axon have also been observed in healthy mammals [161]. The distinction between unipolar and multipolar neurons becomes especially fuzzy when grown outside of their natural environment: Insect neurons, which are unipolarin vivo, become multipolar when grownin vitro[85, 88, 94]. On the other hand, multipolar cells also develop dendrites branching from the axon [85].

The developmental flexibility of soma location in neurons shows that unipolar and multipolar neurons are indeed very similar. In particular, the flexibility of the soma locationin vitroshows, so I would argue, that an evolutionary switch between unipolar and multipolar morphologies is conceivable (and has indeed happened several times throughout evolution, for example the above mentioned dorsal root ganglion cells in the mammalian spinal cord, which developed independently from the insect unipolar shape). The reason for the clear dominance of one or the other morphology in insects and mammals is hence of functional nature, and does not arise from an evolutionary

“dead end”.