mitral cells

How the Nose Knows

Whether we’re awake or asleep, and whether an odor is familiar or new, appears to determine our response to smells. Since we know that smells are highly evocative as well as serving to warn us of danger like smoke or spoiled foods, how the brain perceives odors is of interest to scientists.

Researchers at the University of California, San Diego School of Medicine wondered how sensory representations, in this case the sense of smell, are shaped by the state of an animal and its history. They studied this question in the mouse olfactory bulb, the part of the brain involved in the perception of odors.

Their major conclusion is that the way in which sensory information such as odor is represented isn’t fixed or static, but highly dynamic and flexible. It is modulated by brain state such as wakefulness, experience, even by simple sensory exposure to smells. According to the researchers, his could be the basis of why novel or unfamiliar odors are such noticeable stimuli for humans, compared to familiar odors.

Using a powerful means for monitoring the activity of brain neurons in mammals – called two-photon calcium imaging – the UC San Diego team, headed by Takaki Komiyama, PhD, assistant professor in the UCSD Department of Neurosciences, recorded the activity of specific neuronal cell types in mice, following the activity of the same set of neurons over days, weeks and months.

With this technique, the researchers explored how wakefulness and odor experience modulate the activity of two neuron types in the olfactory bulb, namely mitral cells – the principal neurons of the bulb – and granule cells, very small brain cells that account for nearly half of the neurons in the central nervous system. Granule cells are the major class of interneurons that inhibit mitral cells.

The team imaged the activity of mitral and granule cell populations in awake mice, and subsequently anesthetized the mice to find out how odor representations differ between the awake and anesthetized state. They found that anesthesia increases odor responses of mitral cells. In contrast, granule cell activity is dramatically reduced with anesthesia. These results suggest that, in awake animals, mitral cell odor representations are made sparse by the action of local inhibitory circuits, and that studies in anaesthetized animals may have underestimated the actions of granule cells.

Next, the researchers looked at how mitral cell odor representations in awake mice are shaped by experience. By monitoring the response of same sets of mitral cells to a panel of odors, they found that repeated odor experience causes a gradual lessening of mitral cell responses which accumulates across days. This change is odor-specific – the same mitral cells still respond strongly to other smells. The plasticity, or ability of the neuronal connection to change in strength, recovers gradually over months.

“Intriguingly, this plasticity is not expressed when the mouse is tested under anesthesia, indicating that wakefulness plays a key role in the dynamic nature of mitral cell odor representations,” Komiyama said.

“All available evidence from comparative genetics and neuroanatomy suggests that mouse and human olfactory systems function similarly,” he added. “We have many reasons to believe that what we found in this study in mice directly translates to the perception of odors in humans.”

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Fig.1: 

Figure 7. Reduced Outgrowth of Sensory and Motor Axons in p75NTR-Deficient MiceWhole-mount immunostainings of embryos at dpc 11.0 (A) and 12.0 (B) using the TuJ1 antibody, which recognizes the neuronal-specific protein β tubulin III. p75NTR +/− and p75NTR −/− littermates of the same somite number were compared. Note the reduced outgrowth inp75NTR −/− mutants of intercostal nerves in the thoracic area and spinal nerves in the forelimb. Rostral is to the right, and dorsal is at the top of all panels. Scale bar, 0.5 mm.

Fig. 2

Mitral cells that receive the synapses from the olfactory sensory neuronal axons. Photo courtesy of Charles Greer.