Scientists have enlisted the help of an unusual group of allies – nematode worms – in their quest to better understand, and perhaps even cure, post-traumatic stress disorder (PTSD), a debilitating psychiatric condition that can occur in people who have experienced or witnessed a distressing event such as a natural disaster, serious accident, armed conflict or other violent personal assault.
Researchers from the Hebrew University of Jerusalem, in Israel, are using Caenorhabditis elegans nematodes, each about one millimetre long, to study how unpleasant memories are retrieved and used to generate rapid and protective stress responses, which increase animal survival prospects when facing imminent threat.
Reporting in the journal Current Biology, the scientists say C. elegans nematodes are especially well qualified for this work because “the wiring” of their neural system, comprising 302 neurons, has been fully mapped.
Led by geneticist Alon Zaslaver, the researchers found that even a very basic animal such as the nematode can learn from past experience.
They add that the worms “exhibit a range of learning and memory abilities, including associative memory, which can be studied at a single-neuron resolution”. The mere retrieval of unpleasant memories, they add, induces “rapid, systemic, and protective responses”, which provides a “significant fitness advantage” when facing adversity.
The researchers were also able to pinpoint the exact neurons that form and store memory, and map the physiological changes the worms undergo when they retrieve memories to cope with imminent hardships.
Taking the example of Pavlov’s dogs, the scientists used scents to train the worms to form associative memories.
In the 1890s, Russian physiologist Ivan Pavlov used dogs and food to discover links between instinctive or unconditional, and learned or conditional responses.
The worms were trained using isoamyl alcohol, which has a smell they find attractive.
Instead of feeding the worms, as Pavlov did with his dogs, Zaslaver explains, “we starved them for a day, and instead of ringing a bell, we sprayed a scent that the worms like. We hoped that by linking this odour with hunger, the worms would learn that from now on this pleasant odour signals a distressed situation.”
A day after this training, the scientists fed the worms and sprayed the alcohol again.
The worms quickly entered into a defensive mode and turned on their stress-protective genes. All this happened as soon as they encountered the formerly pleasant scent.
“However, when we again subjected the worms to starvation, they were better able to survive the hardship than before their associative-learning training,” Zaslaver says.
Speeding up their systemic stress-response programs ultimately increased their survival chances when facing subsequent dire conditions.
“In a way, their PTSD had helped them,” he says.
Surprisingly, the researchers found, the new scent memory became stable. Exposing trained worms to the odour in the presence of food did not lead to memory extinction when they were challenged again six or 24 hours later.
Using the C. elegans worm allowed the researchers to “pinpoint the exact neurons that hold associative memories”, Zaslaver says. “It’s very rare that you can look at a neuron and say ‘here, here is the memory’!”
Having located the neurons, Zaslaver and colleagues then genetically engineered new worms with “fight or flight” neurons that could be activated simply by shining a light on them (an approach known as optogenetics), without exposing them to the isoamyl alcohol scent.
When the neurons containing starvation memories were activated, the worms immediately moved into stress mode.
The researchers write that organisms’ capacity to anticipate future conditions “is key for survival”.
“Thus, evoking stressful memories, stored within individual sensory neurons, allows animals to anticipate upcoming dire conditions and provides a head start to initiate rapid and protective responses that ultimately increase animal fitness.”