I met Cornelia Bargmann at a summer school in 1998. She gave a fantastic presentation on very elegant experiments in the roundworm Caenorhabditis elegans. The studies covered all levels from genes to neurons and behavior. Ever since then, when her work popped up on my radar, what I have seen was always of that elegant, beautiful quality I experienced almost 15 years ago now. So obviously, I was very much looking forward to her talk at this year's Society for Neuroscience meeting.

Cori started her talk by explaining how there is no genetic determinism and that all behavioral (and psychological) traits arise through an interplay of genes and environment. In this interaction, only rarely stable states are attained. Rather, neural circuits are dynamic and generate varying behavioral states.

She went on to show how animal model systems are valid research subjects because of the evolutionary connection that all animals share with humans. In fact, many of the genes involved in neural function are present already in simpler animals, including invertebrates nd are most often also functioning in an identical way. The nervous system of her model system, the worm C elegans, consists only of 302 neurons (compared to about 100 billion in humans) whose connectome has been completely mapped out (in 1986).

In a historical overview Cori then illustrated the simple concept of innate, fixed behaviors which later hat to be given up in favor of a concept that describes behaviors as more dynamic and flexible. Intriguingly, she described the simple, innate concept as an input-output system, in which the animals respond to external stimuli with predictable, stereotypic responses. For instance, diacetyl leads to positive chemotaxis in worms, very similar to how light leads to positive phototaxis in insects (such as the flies on our poster). Because of the reliable reproducibility of the behavior, it was possible to use genetic techniques to tease apart the mechanisms by which the odor elicits the behavior. Surprisingly, on one of her slides, the called these responses 'actions'...

In the more refined model she includes the state of the animal (motivation, memory) as the important determinant of behavior, rather than the environmental stimuli. She explained that the neural circuits of the worm constitute a set of networks which provide the animal with a set of different behavioral options among which the animal decides using environmental information. This is amazingly congruent with the concept we have deduced from our fly and snail experiments.
Experiments on the worm's social behaviors were presented as the evidence giving rise for that concept. C. elegans sometimes aggregates into groups. Aggregation has a much higher incidence of occurring in times of stress. With more optimal conditions, the worms will segregate and disperse into solitary animals. In addition to the environmental regulators on aggregation, there are also genetic factors that influence the way in which the environmental factors regulate aggregation: in the same environment, different genetic make-ups lead to different aggregation behavior. Using genetic mapping strategies, the researchers identified two genes contributing to the different aggregation behaviors. One (NPR-1)  is high in solitary animals and low in social strains and the other (glb-5) vice versa. The former being a neuropeptide receptor and the latter involved in oxygen perception. Neuropeptides (similar to biogenic amines) act as neuromodulators, i.e., they have the ability to regulate the behavior of a large number of neurons around their release site. NPR-1 one is expressed in many neurons, but required only in a single pair of neurons to regulate aggregation behavior, the RMG neurons. RMG neurons are connected to a large number of neurons via electrical synapses (gap junctions). She called these neurons a gap junction hub. Using the connectome, they were able to understand how the RMG neurons regulate aggregation behavior, by interacting with the neurons they are connected to. RMG sits at th center of a network of sensory neurons providing input to them: 1. the URX neuron sensing oxygen (via glb-5). 2. The ASK, detecting C3 pheromones. 3. ADL detect C9 pheromones and 4. Four other sensory inputs she didn't specify in detail. The three input neurons she described all show differences in social vs. solitary strains. RMG then regulates aggregation behavior via chemical synapses connecting it to motor neurons.

In the last part of her talk she described both aggregation and dispersal are both active behaviors and that it is the state of the animal that determines which of those are activated. For instance, a solitary animal responds with an escape response to C9 pheromone, whereas social animals respond with aggregation. In solitary strains, ADL neurons mediate C9 elicited avoidance (the same neurons that lead to aggregation in social animals). Avoidance is mediated by ADL's chemical synapses whereas its gap junctions are required for aggregation. NPR-1, via it's effect on RMG regulates the approach/avoidance behaviors underlying aggregation and dispersal.


In conclusion, I can clearly state that Cori did not disappoint my high expectations: she showed very elegant experiments which dissected superficially simple behaviors into their biological constituents. It is rewarding to see how her description of the neural circuits providing the animal with behavioral alternatives matches the concepts we are developing in our lab. She also emphasized how connectomes are necessary but by now means sufficient for understanding brains, because the connectome can be rearranged and modulated by neuromodulators into many different states which constitute the basis upon which environmental stimuli exert their effects.