November 29, 2023

Dating Back to Pavlov: New Twists in Behavioral Association Theories

Author of the paper is Ahmed Roman, who worked on the task as an Emory graduate student and is now a postdoctoral fellow at the Broad Institute. Konstaintine Palanski, a previous college student at the University of Toronto, is also an author.
The conditioned reflex
More than 100 years ago, Ivan Pavlov found the “conditioned reflex” in animals through his experiments on dogs. After a pet dog was trained to associate a sound with the subsequent arrival of food, the dog would start to salivate when it heard the sound, even prior to the food appeared.
About 70 years later, psychologists developed on Pavlovs insights to establish the Rescorla-Wagner model of classical conditioning. This mathematical model describes conditioned associations by their time-dependent strength. That strength increases when the conditioned stimulus (in Pavlovs canines case the noise) can be utilized by the animal to decrease the surprise in the arrival of the unconditioned action (the food).
Such insights assisted set the phase for contemporary theories of support knowing in animals, which in turn enabled support learning algorithms in artificial intelligence systems. Lots of mysteries stay, including some associated to Pavlovs initial experiments.
After Pavlov skilled pet dogs to associate the noise of a bell with food he would then repeatedly expose them to the bell without food. During the first few trials without food, the pets continued to salivate when the bell rang. If the trials continued enough time, the dogs “unlearned” and stopped drooling in reaction to the bell. The association was stated to be “snuffed out.”.
Pavlov discovered, nevertheless, that if he waited a while and after that retested the canines, they would once again salivate in response to the bell, even if no food existed. Neither Pavlov nor more current associative-learning theories might precisely explain or mathematically model this spontaneous recovery of a snuffed out association.
Teasing out the puzzle.
The one-millimeter roundworm only has about 1,000 cells and 300 of them are nerve cells. That simplicity provides researchers with a basic system to evaluate how the animal discovers.
Earlier experiments have developed that C. elegans can be trained to prefer a cooler or warmer temperature level by conditioning it at a particular temperature with food. In a common experiment, the worms are put in a petri dish with a gradient of temperatures however no food. Those trained to choose a cooler temperature will transfer to the cooler side of the meal, while the worms trained to prefer a warmer temperature go to the warmer side.
However just what do these results suggest? Some believe that the worms crawl toward a specific temperature level in expectation of food. Others argue that the worms merely become habituated to that temperature, so they choose to hang out there even without a food benefit.
The puzzle could not be fixed due to a significant limitation of many of these experiments– the prolonged amount of time it takes for a worm to traverse a nine-centimeter petri dish searching for the preferred temperature level.
Measuring how finding out changes over time.
Nemenman and Ryu looked for to conquer this constraint. They wished to establish an useful method to specifically determine the dynamics of knowing, or how finding out changes gradually.
Ryus lab utilized a microfluidic device to diminish the experimental model of nine-centimeter petri dishes into four-millimeter droplets. The scientists might quickly run experiments on numerous worms, each worm enclosed within its specific bead.
” We could observe in real time how a worm crossed a direct gradient of temperature levels,” Ryu states. “Instead of awaiting it to crawl for 30 minutes or an hour, we might much more rapidly see which side of the droplet, the warm side or the cold side, that the worm preferred. And we could likewise follow how its preferences changed with time.”.
Their experiments validated that if a worm is trained to associate food with a cooler temperature it will relocate to the cooler side of the droplet. With time, however, with no food present, this memory preference relatively decomposes.
” We found that unexpectedly the worms wished to spend more time on the warm side of the bead,” Ryu says. “Thats unexpected since why would the worms establish a different preference and even avoidance of the temperature level they had concerned relate to food?”.
Ultimately, the worm begins returning and forth between the cooler and warmer temperature levels.
The researchers assumed that the worm does not just forget the positive memory of food associated with cooler temperature levels however rather starts to negatively associate the cooler side with no food. That stimulates it to head for the warmer side. Then as more time passes, it starts to form a negative association of no food with the warmer temperature level, which combined with the residual positive association to the cold, makes it move back to the cooler one.
” The worm is constantly finding out, all the time,” Ryu discusses. “There is an interplay between the drive of a positive association and an unfavorable association that causes it to begin oscillating between cold and warm.”.
” Its like when you lose your secrets”.
Nemenmans team developed theoretical equations to describe the interactions over time between the 2 independent variables– the favorable, or excitatory, association that drives a worm towards one temperature and the negative, or inhibitory, association that drives it far from that temperature.
” The side that the worm gravitates toward depends upon when precisely you take the measurements,” Nemenman describes. “Its like when you lose your secrets you may inspect the desk where you typically keep them. You run around various locations looking for them if you do not see them there right away. If you still dont find them, you return to the initial desk figuring you simply didnt look hard enough.”.
The scientists duplicated the experiments under various conditions. They trained the worms at different starting temperatures and starved them for various durations of time before evaluating their temperature level preference, and the worms behaviors were correctly forecasted by the formulas.
They also checked their hypothesis by genetically modifying the worms, knocking out the insulin-like signaling pathway known to serve as a negative association path.
” We annoyed the biology in particular ways and when we ran the experiments, the worms behavior changed as anticipated by our theoretical model,” Nemenman states. “That offers us more confidence that the design shows the underlying biology of learning, at least in C. elegans.”.
The researchers hope that others will evaluate their model in research studies of bigger animals throughout types.
” Our model offers an alternative quantitative model of discovering that is multi-dimensional,” Ryu says. “It describes outcomes that are difficult, or in some cases impossible, for other theories of classical conditioning to explain.”.
Referral: “A dynamical model of C. elegans thermal preference exposes independent excitatory and inhibitory learning pathways” by Ahmed Roman, Konstantine Palanski, Ilya Nemenman and William S. Ryu, 20 March 2023, Proceedings of the National Academy of Sciences.DOI: 10.1073/ pnas.2215191120.
The research study was moneyed by the Natural Sciences and Engineering Research Council of Canada, the Human Frontier Science Program, and the National Science Foundation.

The scientists performed experiments on C. elegans, a roundworm with simply 300 nerve cells, that uses a simple laboratory model for studying how an animal discovers.
A multi-dimensional design to explain the knowing procedure of an animal in time.
Physicists have established a dynamic model of animal habits that might clarify the long-standing secrets of associative learning, going back to Pavlovs popular canine experiments. The study, which was carried out on the commonly utilized lab organism C. elegans, was published in the Proceedings of the National Academy of Sciences (PNAS).
” We revealed how found out associations are not moderated by just the strength of an association, however by multiple, almost independent pathways– at least in the worms,” says Ilya Nemenman, an Emory teacher of physics and biology whose lab led the theoretical analyses for the paper. “We expect that comparable outcomes will hold for larger animals as well, including maybe in people.”
” Our design is multi-dimensional and dynamical,” includes William Ryu, an associate professor of physics at the Donnelly Centre at the University of Toronto, whose laboratory led the speculative work. “It describes why this example of associative learning is not as easy as forming a single favorable memory. Instead, its a continuous interaction in between favorable and unfavorable associations that are taking place at the very same time.”

In a typical experiment, the worms are placed in a petri dish with a gradient of temperature levels however no food. Those trained to choose a cooler temperature will move to the cooler side of the meal, while the worms trained to prefer a warmer temperature go to the warmer side.
Some think that the worms crawl towards a particular temperature level in expectation of food. Others argue that the worms simply end up being habituated to that temperature, so they prefer to hang out there even without a food reward.
The researchers assumed that the worm does not just forget the positive memory of food associated with cooler temperatures however rather starts to negatively associate the cooler side with no food.