Researchers have discovered that in the brain of the fruit fly, the sensations of pleasant and unpleasant smells are not opposites but are computed by entirely separate and distinct neural circuits. A team at the RIKEN Center for Brain Science in Japan found that while repulsive odors are processed through a straightforward excitatory pathway, attractive odors are processed using a more complex system involving local inhibition, revealing a fundamental principle of how the brain assigns positive or negative value to sensory information.
This new understanding of sensory processing challenges the long-held assumption that the brain might evaluate good and bad stimuli on a single continuum. By mapping the specific neural pathways in the fly’s brain, the study provides a detailed blueprint for how “hedonic valence”—the innate sense of attraction or aversion—is calculated at a cellular level. Because the olfactory systems of insects and mammals share deep evolutionary roots, these findings offer a powerful new framework for investigating the far more complex circuits that govern emotion, decision-making, and perception in the human brain.
A Model System for Scent
The sense of smell, or olfaction, is one of the oldest sensory systems, critical for finding food, avoiding danger, and identifying mates. In complex organisms like humans, the sheer number of odors and the vast web of interconnected neurons make it incredibly difficult to decipher how the brain translates a chemical signal into a judgment. The human brain contains billions of neurons, and understanding their precise wiring remains a monumental task. To simplify the problem, scientists often turn to model organisms where the neural architecture is more manageable yet operates on similar principles.
The fruit fly, Drosophila melanogaster, serves as an ideal subject. Its brain is small enough that researchers can identify every single olfactory neuron and map its connections, a complete wiring diagram known as a connectome. Despite its relative simplicity, the fly’s olfactory system is remarkably sophisticated, capable of guiding the insect through a complex world of chemical cues. This tractability allows researchers to link specific neural circuits directly to observable behaviors, providing a level of precision that is not yet possible in vertebrates.
Advanced Imaging and Modeling Techniques
To untangle the fly’s odor-processing circuits, the research team, led by Hokto Kazama, employed a suite of cutting-edge technologies. They needed to see exactly which neurons were active when a fly was exposed to a particular scent and understand how those neurons communicated with each other. This required observing the entire relevant brain region at once while also being able to manipulate individual cells.
Mapping Neural Activity
The scientists focused their investigation on a brain region called the lateral horn, which is known to be involved in processing innate odor preferences. To visualize neural signals in real-time, they combined two-photon microscopy with optogenetic cell labeling. This powerful combination allowed them to make all neurons in the lateral horn light up and report their activity as a fly experienced different smells. Optogenetics involves genetically modifying neurons to express light-sensitive proteins, effectively making them responsive to light, which can be used for both monitoring and control.
Building a Digital Brain
In parallel with their live imaging experiments, the researchers constructed a detailed network model based on the fruit fly’s connectome. This computational model simulated the activity of the neurons and their connections, allowing the team to generate hypotheses about how the circuit performed its calculations. By feeding the model information about how neurons responded to specific odors, they could predict how the entire system would behave and, crucially, pinpoint which connections were responsible for classifying an odor as either appealing or aversive. This digital twin of the fly’s brain circuit was essential for making sense of the complex biological data.
Distinct Circuits for Good and Bad Smells
The team’s central discovery was that the brain does not treat pleasure and displeasure as two sides of the same coin. Instead, it uses fundamentally different circuit motifs to process these two opposing experiences. The model predicted, and experiments confirmed, that the computations for “bad” smells were simpler than those for “good” smells.
How the Brain Encodes Displeasure
When a fly detects an unpleasant odor, such as chemicals associated with stress or decay, the signal is processed through a relatively direct “feedforward excitation” pathway. Neurons that recognize the repulsive scent directly activate downstream neurons in the lateral horn, creating a strong and clear signal to avoid the source. This straightforward circuit ensures a rapid and reliable response to potential threats.
The Complexity of Pleasure
In contrast, the circuit for pleasant odors was more intricate. The model revealed that in addition to feedforward excitation, the representation of an attractive scent required “local inhibition.” This means that while some neurons were being excited, other nearby neurons were actively silenced. This additional inhibitory layer carves out a more specific and nuanced representation for attractive smells, like those from fermenting fruit. The discovery that the brain adds a layer of complexity to process positive stimuli suggests that “good” is not merely the absence of “bad” but an entirely separate and actively constructed computation.
Verifying the Circuit’s Function
A key strength of the study was the team’s ability to test their model’s predictions in living flies. Using optogenetics, they could precisely control individual neurons, turning them on or off with light to see how it affected the fly’s behavior. This allowed them to move beyond correlation and establish causation, proving that the circuits they identified were in fact responsible for odor preference.
In one definitive experiment, the model predicted that silencing a specific inhibitory circuit would make a fly dislike an odor it would normally find attractive. When the researchers performed this experiment, the fly’s behavior changed exactly as predicted. By artificially manipulating the “pleasant” circuit, they could effectively turn a good smell into a bad one from the fly’s perspective. This functional validation confirmed that their understanding of the distinct circuits was correct and demonstrated the remarkable predictive power of their integrated imaging and modeling approach.
Implications for Human Neuroscience
While the brain of a fruit fly is vastly different from that of a human, the fundamental principles of neural computation are often conserved through evolution. The finding that positive and negative valence are handled by separate, asymmetric circuits provides a new lens through which to examine sensory processing in more complex organisms. It suggests that our own brains may use similar strategies to distinguish pleasure from pain, or attraction from aversion.
This research could inform our understanding of how the human brain appreciates the flavor of food, reacts to threatening smells, and makes value-based decisions. It also opens up new avenues for studying psychiatric conditions where sensory processing and emotional valence are disrupted, such as anxiety and depression. By revealing the specific logic of a core brain function in a simple animal, this work provides a critical stepping stone toward deciphering the neural basis of perception and emotion in ourselves.