In their new study published in BMC Biology
Srinivasan et al
] systematically compared the neural circuits involved in detecting noxious stimuli in six different nematode strains. To characterize these circuits, they determined which single-cell ablations affected avoidance of particular stimuli. For example, nematodes of all species tested showed strong avoidance of the odorant 1-octanol. In this case, all strains showed similar ablation phenotypes: killing ASH strongly impaired octanol avoidance, whereas ablation of other amphid neurons had no significant effect. Likewise, light mechanical stimulation of the nose produced comparable avoidance responses in all species, although habituation was much faster in one species, Cruznema tripartitum
. However, whereas three neuron types, ASH, FLP and OLQ, affect nose touch avoidance in C. elegans
, in a different species (Caenorhabditis
. sp. 3) only ASH is important (Figure ). A similar but opposite effect was observed for osmotic avoidance, which in C. elegans
is mediated solely by ASH, but was found to involve the ADL and ASH neurons in Pristionchus pacificus
(Figure ). Surprisingly, P. pacificus
was one of several species tested that responded more weakly to the high osmotic stimulus despite the extra neurons in its circuit. A clustering analysis based on the avoidance responses of the various species in the study revealed not only examples of correlation between behavioral similarities and phylogenetic proximity, but also cases of greater behavioral differences between closely related species than between more distantly related ones. Thus, evolutionary remodeling of these sensory circuits might occur readily in response to natural selection.
Figure 1 Evolutionary neuronal remodeling between nematode strains. (a) In C. elegans three sets of neurons, ASH, FLP and OLQ, mediate aversion to light mechanical stimulation of the nose (top). The same response was found to require ASH alone in C. sp. 3 (bottom). (more ...)
What do ablation results tell us about how nociceptive circuits have been remodeled during nematode evolution? One possibility is that particular neurons might alter or even lose functionality in the course of evolution. One should be cautious, however, as the components of a neural circuit are not necessarily limited to those neurons whose ablation early in development impairs the circuit's function. During development, an ablated animal can sometimes compensate for a missing neuron, for example by reorganizing the remaining neurons in the circuit. Moreover, recent examples demonstrate that it can be easier for a circuit to compensate for a missing neuron than for an inactive one, even when the neuron's function is absent throughout development [7
]. Ablation studies can be said to define the group of neurons whose functions are most critical for a given behavior. Thus, if ablation of a neuron no longer affects the function of a particular circuit, this might not indicate a change in the overall function of the neuron, but might indicate its importance or dispensability for the circuit.
Another recent study comparing feeding behavior in four nematode species [9
] provides some insight into how such changes might occur. Nematodes feed by pumping food through a muscular pharynx, which is controlled by the pharyngeal nervous system. Three motor neurons (MC, M3 and M4) appear to have particularly important roles in controlling pharyngeal contraction in all species. However, in one species, Panagrolaimus
sp. PS1159, a fourth motor neuron, M2 (which has no known function in the other species), has apparently acquired a role in controlling contraction of the pharyngeal isthmus. Likewise, the M4 neuron controls contraction of the pharyngeal isthmus and terminal bulb in most species; in C. elegans
, however, it appears to have lost the latter function. Interestingly, the mechanism for this change in M4 function appears to involve silencing of M4's terminal bulb synapses during evolution. It is possible that similar types of change might occur in sensory circuits to reconfigure the roles of individual neurons in particular sensory modalities.
Clearly, ablation studies are only a first step in understanding how behavior evolves in nematodes. With modern electron microscopy and computational methods, it should be practical to reconstruct the neuroanatomies of other nematodes at the single-cell level and compare the connectivity patterns with those of C. elegans
. With the development of transgenesis protocols for other nematode species [10
], it will also be possible to use genetically encoded sensors to probe the activity patterns of homologous neural circuits in a range of nematodes. In the near future, there is a real possibility of understanding the detailed genetic and cellular mechanisms by which nematode nervous systems are remodeled during evolution.