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 Mice Have Distinct Subsystem to Handle Smell Associated With Fear

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Date posted: 23/07/2012

A new study finds that mice have a distinct neural subsystem that links the nose to the brain and is associated with instinctually important smells such as those emitted by predators. That insight, published online this week in Proceedings of the National Academy of Sciences, prompts the question whether mice and other mammals (such as humans) have specially hardwired neural circuitry to trigger instinctive behavior in response to certain smells.

In the series of experiments and observations described in the paper, the authors found that nerve cells in the nose that express members of the gene family of trace amine-associated receptors (TAAR) have several key biological differences from the much more common and diverse neurons that express members of the olfactory receptor gene family. Those other nerve cells detect a much broader range of smells, said corresponding author Gilad Barnea, the Robert and Nancy Carney Assistant Professor of Neuroscience at Brown University.

The differences between TAAR neurons and olfactory receptor neurons led Barnea and his co-authors to conclude that they form an independent subsystem for certain smells.

"Our observations suggest that the TAAR-expressing sensory neurons constitute a distinct olfactory subsystem that extracts specific environmental cues that then elicit innate responses," Barnea said.

The newly found differences include the way TAAR neurons are wired to structures called glomeruli in the olfactory bulb, which is the brain area that initially processes smells. The glomeruli relay smell signals deeper into the brain where the perception of smell occurs and behavioral responses are initiated.

Graduate students Mark A. Johnson and Lulu Tsai at the Barnea laboratory visualized TAAR neurons in the nose and their projections to the olfactory bulb by generating specific antibodies that could detect TAAR proteins in these neurons. They found that while neurons expressing a given olfactory receptor connect to only two glomeruli, neurons that express a given TAAR connect to four to six glomeruli. They also found that while olfactory receptor neurons connect to glomeruli throughout the olfactory bulb, TAAR glomeruli tend to be clustered within an area at the top of the bulb. That area was implicated in instinctual behaviors by previous research.

In another experiment they found that the TAAR axons leading to glomeruli at the top of the bulb express a cell adhesion molecule that is associated with olfactory receptor axons leading only to glomeruli at the bottom part of the olfactory bulb.

What convinced Barnea and his colleagues that TAAR neurons constitute an olfactory subsystem were differences in how these neurons choose the receptor gene that they express. They used mice in which one TAAR gene is swapped with a marker that turns the cell blue. When the same strategy was used in olfactory receptor-expressing neurons, the blue marker was switched off and another olfactory receptor gene was selected. By contrast, TAAR-expressing neurons did not turn off the blue marker. They selected another TAAR gene, but continued to be stained blue.

This observation led Barnea and longtime collaborator Stavros Lomvardas of the University of California-San Francisco to identify several other differences between TAAR neurons and olfactory receptor neurons in how the neurons carry out gene expression.

"The logic of gene choice in TAAR neurons is different," Barnea said. "Their patterns of projection [to the bulb] are different, and the mechanisms that control their projections are different. Altogether these observations suggest that it's a different subsystem."

See the full Story via external site: www.sciencedaily.com



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