The structure and connectivity of the nervous system of the nematode Caenorhabditis elegans has been deduced from reconstructions of electron micrographs of serial sections. The hermaphrodite nervous system has a total complement of 302 neurons, which are arranged in an essentially invariant structure. Neurons with similar morphologies and connectivities have been grouped together into classes; there are 118 such classes. Neurons have simple morphologies with few, if any, branches. Processes from neurons run in defined positions within bundles of parallel processes, synaptic connections being made en passant. Process bundles are arranged longitudinally and circumferentially and are often adjacent to ridges of hypodermis. Neurons are generally highly locally connected, making synaptic connections with many of their neighbours. Muscle cells have arms that run out to process bundles containing motoneuron axons. Here they receive their synaptic input in defined regions along the surface of the bundles, where motoneuron axons reside. Most of the morphologically identifiable synaptic connections in a typical animal are described. These consist of about 5000 chemical synapses, 2000 neuromuscular junctions and 600 gap junctions.
The functional properties of a nervous system are largely determined by the characteristics of its component neurons and the pattern of synaptic connections between them. Although great progress has been made this century in understanding the manner in which information is coded within a neuron and the process of information transmission between neurons via synapses, little is currently known about the detailed connectivity of networks of neurons. The reason for this is simply that a nervous system is an enormously complex organ. In the vertebrate cerebellum alone, it has been estimated that there are more than 1010 neurons (Braitenberg & Atwood 1958) each making many thousands of synaptic contacts.
We have undertaken a complete reconstruction of a nervous system from electron micrographs of serial sections. We have been able to do this by using a very simple, small nervous system, that of the soil nematode Caenorhabditis elegans. The simplicity and consistency of structure of the nematode's nervous system attracted the attention of several neuroanatomists at the turn of the century. Richard Goldschmidt was perhaps the most notable of these; he attempted to reconstruct the nervous system of the large parasitic nematode Ascaris lumbricoides from serially sectioned material. Goldschmidt and his contemporaries produced detailed and accurate descriptions of the sensilla, the ganglia and the process tracts (Chitwood & Chitwood 1974), but the limited resolution of the light microscope prevented them from unambiguously resolving individual processes within bundles. Goldschmidt was convinced that neuron processes anastomosed extensively and that nervous tissue was therefore a syncytial network. He presented a set of intriguing diagrams representing the layout of processes in the Ascaris nervous system in support of his view of the structure of nervous tissue, a view that he vigorously defended (Goldschmidt 1908, 1909). The alternative viewpoint considered that neurons are mono nucleate branched structures and that their processes do not anastomose. It is now clear that this alternative viewpoint, as espoused by his contemporary critics, such as Cajal (1972), was correct. More recent anatomical studies with the electron microscope have finally laid to rest the reticularists' view of the nervous system. We have therefore not tried to interpret Goldschmidt's connectivity diagrams, although we have retained some of the names, given to the sensilla and ganglia, that were used by him and his contemporaries.
In recent years, C. elegans has become an object of intense developmental and genetical study. The highly reproducible sequence of cell divisions that takes place during the development of this organism has allowed the complete cell lineage to be determined from the fertilized zygote to the mature adult (Sulston 1983; Sulston et al. 1983). Each differentiated cell type that is produced at the terminal twigs on the lineage tree is now known. Laser ablation studies have given some insight into the degree of cell autonomy that is involved in determining the pattern of cell divisions and differentiations that occur. Generally it seems that, in C. elegans, cells behave fairly autonomously during development, although there are several well-defined instances where regulative cell-cell interactions have been demonstrated (Sulston & White 1980; Kimble 1981).
C. elegans was originally selected as an organism worthy of extensive developmental studies, partly because it is readily amenable to genetic analysis. Many mutants have been isolated and mapped (Brenner 1974). The mutants that have been isolated exhibit a wide variety of phenotypes: some are morphological, some affect various aspects of development and many exhibit aberrant behaviour. Some of the behavioural mutants have been shown to have defects in muscles (Waterston et al. 1980), but many probably have alterations in the nervous system (Lewis & Hodgkin 1977; Chalfie & Sulston 1981; Hedgecock et al. 1984). It is hoped that a detailed knowledge of the structure of the wild-type nervous system of C. elegans will facilitate the interpretation of the changes that occur in such mutant nervous systems. This may in turn shed some light on the genetic control of the developmental processes that ultimately give rise to the specifically interconnected group of neurons that make up a nervous system.
The reconstructions that are presented in this paper describe the connectivity of all the neurons in the nervous system of the C. elegans hermaphrodite except those in the pharynx, which have been described by Albertson & Thomson (1976). The detailed morphologies of the sensilla in the head have been described by Ward et al. (1975), Ware et al. (1975) and Wright (1980); the structure of the ventral cord has been described by White et al. (1976) and an independent reconstruction of the tail ganglia has been described by Hall (1977). Together these papers give a fairly complete description of the connectivity, topography and ultrastructure of the nervous system in the hermaphrodite. The C. elegans male has a more extensive nervous system than that of the hermaphrodite; most of the 'extra' nervous tissue is situated in the tail. A partial reconstruction of the nervous system in the male tail has been described by Sulston et al. (1980).
The structure of the ventral cord of Ascaris has been deduced from reconstructions of light micrographs of serial sections (Stretton et al. 1978). In spite of the enormous difference in size between these two nematodes (10 cm as against 1 mm for C. elegans), the motoneurons in the ventral cord turn out to be remarkably similar, and it has been possible to identify equivalent motoneuron classes in the two animals. The large size of Ascaris enables electrophysiological techniques to be used in the study of its nervous system. Such studies have identified inhibitory and excitatory classes of motoneuron and have shown that acetylcholine is the neurotransmitter used by the excitatory motoneurons (Johnson & Stretton 1980). The small size of C. elegans precludes such electrophysiological studies but, by analogy, these results may be related to the equivalent neurons in C. elegans and so provide clues as to their functional properties.
Although reconstructions of nervous tissue from electron micrographs can in principle identify all focal synaptic contacts, it is unlikely that the pattern of connectivity obtained would exactly represent the functional synaptic connections between neurons. There is evidence that synaptic transmission mediated by some peptide transmitters acts over a considerable range (Jan et al. 1983), suggesting that these types of synapses may not be localized at discrete focal contacts and therefore would not be seen in electron micrographs. There are other routes by which transmission of information could occur between neurons which are not apparent from reconstructions. Neurohumoral transmission is probably used for transmission over long distances and where many targets may be involved; a good candidate for a neurosecretory neuron has been found in the pharynx (Albertson & Thomson 1976). Short-range transmission may occur by means of electrical leakage currents or by capacitive coupling between processes that run alongside each other for long distances. However, in spite of these limitations, high-resolution reconstructions provide a wealth of information on the synaptic contacts between neurons. Thus, of all the currently available techniques, such reconstructions probably provide the most comprehensive picture of the synaptic circuits of a nervous system such as that of C. elegans.
Because of the large amount of information that is involved in presenting the connectivity data, we have tried to organize its presentation in such a way as to facilitate quick access. The structure of a 'canonical' nervous system is presented, which is in fact a mosaic of several nervous systems. A general description is first given of the structure of C. elegans and some of the salient features of the nervous system. This is followed by a detailed description of each of the neuron classes arranged in alphabetical order in Appendix 1. These descriptions are fairly self-contained and include morphological as well as synaptic data. There are many references in the first section to illustrations in Appendix 1. These appear as the class name followed by a letter, e.g. ASE-a. The lower case letter indicates the diagram referred to in the description of the neuron class ASE.
Web adaptation, Thomas Boulin, for Wormatlas, 2001, 2002