Summary: New research identifies a key mechanism in how the brain distinguishes different smells.
Source: UC Santa Barbara
The delicate fragrance of jasmine is widely enjoyed—in teas, perfumes and potpourri—but when concentrated the same scent can become almost cloying. Part of that aroma comes from skatole, a compound also found in fecal odor, illustrating how complex and context-dependent smells can be.
Smell depends on hundreds of different odorant receptors working together. The stronger an odor activates a given receptor neuron, the more electrical signals that neuron sends to the brain. Researchers at UC Santa Barbara have now shown that, counterintuitively, some of these neurons stop firing once an odor reaches sufficiently high concentrations.
Far from being an error, this sudden silencing—or depolarization block—appears to be a built-in feature that helps the brain identify odors across a wide range of intensities. “It’s a feature; it’s not a bug,” said Matthieu Louis, associate professor in the Department of Molecular, Cellular, and Developmental Biology.
Published in Science Advances, the study challenges long-held ideas about odor encoding. “The same odor can produce very different patterns of active olfactory sensory neurons depending on concentration,” Louis said.
This effect could help explain why a scent changes character as its intensity shifts—think of the difference between the pleasant aroma of a ripe banana at a distance and the artificial, overpowering smell when you are very close.
Humans carry several million sensory neurons in the nose, each expressing one type of odorant receptor. Across the population there are roughly 400 receptor types with overlapping sensitivities. Each odor molecule is like trying on a shoe: some receptors are a perfect fit and respond strongly, others respond weakly or not at all.
As odor concentration rises, more receptors are recruited—those that respond only at higher intensities. Scientists previously assumed receptor responses would simply saturate: neurons would reach a maximum firing rate and remain active. Instead, the UC Santa Barbara team found that the most sensitive neurons can fall silent as stimulus strength increases further, causing active neurons to drop out in a predictable order.
A simple model
Fruit fly larvae provide an excellent system to study olfaction because each sensory neuron expresses a distinct receptor type—21 in total—allowing researchers to observe individual neuron behavior directly.
Graduate student David Tadres studied mutant larvae that initially lacked all smell. By restoring function to a single sensory neuron at a time, he allowed larvae to detect odors only via one receptor and then observed their behavior near an odor source.
Even with a single active olfactory channel, larvae moved toward the odor but stopped at a specific distance and circled the source. When Tadres activated a neuron that was less sensitive to the same odor, the larvae stopped closer. Curious about the cause, he measured the neuron’s electrical activity with electrodes.
As odor concentration increased, neuronal signaling initially rose as expected but then plunged to zero instead of plateauing. That loss of activity explains the circling: beyond a particular concentration, the sensitive neuron became silent and the odor effectively vanished for that sensory input.
“The silencing of the olfactory sensory neuron can readily explain the circling behavior, which had been puzzling,” Tadres said. “This forced us to rethink how odor representations change with concentration.”
Although depolarization block is a known phenomenon—often discussed in the context of epilepsy—researchers had assumed it did not play a role under normal sensory conditions. Observing behavior driven by this effect suggested it is physiologically meaningful in olfaction.
A mathematical model
To understand the mechanism, Tadres and Louis worked with Professor Jeff Moehlis and doctoral student Philip Wong to build a mathematical model. They combined a conductance-based description of neuronal membrane voltage with a model of the odorant receptor’s transduction cascade.
The model incorporated a process known from epilepsy research: sustained strong stimulation can inactivate certain ion channels, preventing spike generation. Wong’s model reproduced the recorded voltage traces and helped explain how sustained high input could shut a neuron off.
“The model matched the electrophysiology data and made it possible to interpret results that were otherwise time-consuming to collect,” Wong said. It also pointed to a specific ion channel, common across many species, as a likely contributor to the depolarization block, raising the possibility that other sensory neurons operate similarly.
The model further predicted hysteresis: neuron behavior depends on whether odor concentration is rising or falling. Measurements confirmed this—once driven into silence by high concentrations, a neuron often stayed inactive until the stimulus fell to very low or zero levels before resuming normal activity.
A better system for smell
These findings show that high odor concentrations can silence the most sensitive receptors, changing how odors are encoded at the periphery. Instead of simply adding more active receptors as concentration rises, the system replaces some high-sensitivity inputs with lower-sensitivity ones, preserving distinctions between different odors even at high intensities.
“If every receptor were active at high concentrations, different odors would become indistinguishable,” Tadres explained. The selective dropout of sensitive neurons maintains sparse and informative patterns that help the brain discriminate odors across wide concentration ranges.
This mechanism likely has survival value: it can prevent dangerous or nutrient-rich substances that share chemical components from becoming confusable when their odors are strong. Louis likened the effect to removing the root note from a chord—altering the perception of the whole sound. In smell, losing successive high-sensitivity neurons changes the sensory “chord,” giving the odor a different meaning at different concentrations.
Overall, the study uncovers a surprising aspect of olfactory coding: depolarization block expands the dimensionality of odor encoding, enabling more robust discrimination in a chemically complex world.
By allowing some neurons to fall silent while others activate, the olfactory system preserves meaningful differences between odors across concentrations—an elegant solution to a fundamental sensory challenge.
About this olfaction research news
Author: Harrison Tasoff
Source: UC Santa Barbara
Contact: Harrison Tasoff – UC Santa Barbara
Image: The image is in the public domain
Original Research: Open access.
“Depolarization block in olfactory sensory neurons expands the dimensionality of odor encoding” by David Tadres et al. Science Advances
Abstract
Depolarization block in olfactory sensory neurons expands the dimensionality of odor encoding
Neurons can enter a silent state called depolarization block after strong, sustained excitation; this phenomenon is often discussed in the context of neurological disorders. Here, we show that peripheral olfactory sensory neurons also undergo depolarization block as a normal component of their function.
Typically, these sensory neurons enter depolarization block at concentrations about three orders of magnitude above their detection threshold, thereby defining receptor tuning across concentration bands. Silencing high-affinity neurons produces sparser peripheral representations at high odor levels, which may enhance perceptual discrimination.
Using a conductance-based model of olfactory transduction coupled to spike generation, we provide numerical and experimental evidence that depolarization block can arise from the slow inactivation of sodium channels—a mechanism that could operate across many types of sensory neurons.
The presence of ethologically relevant depolarization block in olfactory sensory neurons adds an additional dimension to peripheral odor encoding, helping the nervous system distinguish smells across a broad range of concentrations.