Paper #13 - System-wide rewiring underlies behavioral differences in predatory and bacterial-feeding nematodes
Summary: In Pristionchus pastoris - a nematode related to C. elegans, but also capable of eating other worms instead of just bacteria - how does the the pharyngeal nervous system differ?
They used serial thin-section TEM to reconstruct the connectome of P. pacificus' pharynx. They reconstructed the pharyngeal nervous system from three animals, although they had missing sections in the nerve ring in the third animal, so its used 'for homology assessment only.'
First off, like C. elegans, P. pacificus has 20 neurons in the pharynx, and they're essentially in the same places and have the same morphology.This is striking, as the authors note in the discussion that these strains are diverged by >100 million years.
More of the neuron types (13/14) synapse onto muscles in P. pacificus, as compared to 8/14 in C. elegans.
How else do you quantify differences in wiring? They note some very specific changes that honestly, I really don't understand how to interpret, perhaps because I know jack-all about C. elegans feeding and less about P. pacificus. Things like 'I2 has a feedback loop with M1 and is presynaptic to I1, which is consistent with a role in coordinating corpus and tooth contractions during predation.' How do you tell if a wiring pattern is 'consistent' with known behavior?
Another approach they take to quantifying differences is based on degree distributions and centrality. They look at four metrics of centrality (node degree, closeness , betweenness and pagerank), and determine first that I1 and I2 are the most different in their degree (in-degree? out-degree? total degree? not clear...). They are connected to 5 and 9 more neurons (and muscles? I'm not clear on whether NMJs are included as edges in the network or not) in P. pacificus than in C. elegans.
There are again differences in the other centrality metrics for each neuron between C. elegans and P. pacificus, but I'm not sure how to interpret them.
They then go on to define " 'focused centrality analysis' to define which parts of a network are most important for a node." They simulate random walks on their network.*They then ask for a particular focal node (presumably the start of the random walk?), what proportion of walks to a secondary node occur via the shortest path and what occur via longer paths (they call this 'indirect information').
All told, I'm not sure I understand the value of their analysis of the centrality of various nodes in the network. Regardless, mapping the pharyngeal connectome is an important piece of work and the demonstration of immense rewiring, despite conserved neuronal morphology, is clearly an important discovery.
In the discussion, they reference Prinz, et al. (2004), which I will admit I was kind of thinking about while reading this paper. Prinz and co simulated a 3-neuron network with a bajillion synaptic weights and a bajillion different neuronal properties, and found that many disparate areas of parameter space would yield 'indistinguishable' network activity. So could the rewiring they observe simply be neutral drift to another configuration that produces the same output? I think the answer is pretty clearly no! P. pacificus has to move its tooth in order to eat other worms - a behavior C. elegans simply doesn't do, and therefore this network has to be capable of doing something new. But I'm still not clear how this extra behavior is accessible based on the change in wiring.
Questions I still have:
- As a reader, I wish this paper could have connected to function a little bit more. In large part, it's just my lack of background - I don't know how different in terms of mechanical behavior C. elegans and P pacificus feeding are, nor do I really have much grasp on how different muscles need to be recruited in P. pacificus for eating worms vs eating bacteria. Maybe I just need to go back and read other papers first before I can really grasp this one.
- What would voltage imaging look like in the pharyngeal network during different feeding modes?
- Perhaps I missed it, but I didn't see a discussion of variation between animals. They did 3 animals, and thus understanding how different these animals are (and where the differences arise) would be quite valuable!
- I'm not clear how much of the difference in wiring in C. elegans and P. pacificus is due to changes in chemical synapses and how much is due to changes in gap junctions.
* I found this part of the paper confusing, as the details (which seem to be crucial to the interpretation of the metric) are confined to the methods section. More generally, to me random walks don't seem to be the most reasonable choice for a model of information flow in an electrical network.