By using an experimental trick to activate certain sets of neurons and effectively substitute activation of these cells for positive or negative experiences, researchers have been able to identify neurons in the fruit fly Drosophila that are responsible for assigning value to stimuli during so-called associative learning. The findings, which advance our understanding of how, at the cellular level, we learn to associate cues with positive and negative experiences, are reported by Andre Fiala and colleagues at the University of Würzburg in Germany and appear in the September 5th issue of Current Biology, published by Cell Press.
Researchers Identify Neurons That
Assign Value During Learning
During associative learning, animals learn to change their behavior in response to a particular stimulus that would otherwise have a neutral influence on behavior. For example, if an animal such as a fruit fly learns to associate a particular odor with a punishing stimulus, the odor itself can become repulsive. Conversely, an odor associated with a reward can become attractive. Despite its relatively modest brain complexity, the fruit fly larva is able to perform such associative-learning tasks. Because of its neuronal simplicity and the fact that it can be genetically manipulated, the fruit fly offers a favorable study case to address a principal question in the field of learning and behavior: Which neurons attribute attractive or aversive values to so-called neutral stimuli, such as odors, in the course of associative learning?
Past work had indicated that certain neurotransmitters played key roles in assigning attractive or aversive values to neutral stimuli--for example, neurons expressing dopamine are required for aversive learning, whereas neurons expressing another neurotransmitter, octopamine, are required for appetitive learning (association of a stimulus with a reward). However, it was unclear whether a common set of neurons were responsible, or whether attractive and aversive values were assigned to neutral stimuli by independent sets of neurons.
To tackle this question, the researchers engineered transgenic fruit flies that express in distinct nerve cells a special ion channel, "channelrhodopsin-2," whose activity is light-sensitive (the protein is normally found in green algae). As a result of expressing channelrhodopsin-2, neurons could be activated simply by illuminating fruit fly larvae with blue light. This tool allowed the researchers to test whether such an activation of certain neurons can actually substitute for external stimuli--for example, reward or punishment--in an associative-learning experiment. The researchers found that if an odor is presented while a group of dopamine-releasing neurons are experimentally light-activated, the larvae learn to avoid this odor in a later test, despite the fact that no negative stimulus was presented to the larvae along with the odor. Conversely, if an odor is presented while a different group of neurons--releasing octopamine and/or tyramine--are experimentally light-activated, the odor becomes attractive. These findings demonstrate that antagonistic subsets of neurons are responsible for assigning positive or negative values to odor stimuli. It will be of interest to see whether this principal concept of antagonistic neuronal populations mediating positive or negative values during learning holds true for much more complex mammalian brains as well.
The researchers include Christian Schroll, Thomas Riemensperger, Daniel Bucher, Julia Ehmer, Thomas Völler, Karen Erbguth, Bertram Gerber, Erich Buchner, Georg Nagel, and André Fiala of Universität Würzburg Biozentrum in Würzburg, Germany; Thomas Hendel of Universität Würzburg Biozentrum in Würzburg, Germany and Max-Planck-Institut für Neurobiologie in Martinsried, Germany.
This work was supported by the Deutsche Forschungsgemeinschaft (SFB 554, GRK 1156, and a Heisenberg Fellowship to B.G.).
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