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Abstract:
The sense of smell allows mammals to distinguish an enormous
number of volatile chemicals of varied size and shape. Remarkably,
the discriminatory power of this sense is such that even a slight
change in the structure of an odorant can dramatically alter its
perceived odor. To explore how this is accomplished, we have taken
a molecular approach, asking first how odorants are detected and
then using genes encoding detectors to explore how sensory
information is encoded in the olfactory system. In initial studies,
we identified a multigene family encoding ~1000 odorant receptors
(ORs) that are expressed by neurons in the nasal olfactory
epithelium (OE). Each OE neuron expresses only one OR gene. We
found that neurons with the same OR are scattered in the OE, but
that their axons converge in a few specific glomeruli in the
olfactory bulb, giving rise to stereotyped map of OR inputs.
Recently, we used a combination of calcium imaging of single OE
neurons and single cell RT-PCR to identify ORs that recognize
odorants with related structures, but varied odors. Our studies
show that the olfactory system uses a combinatorial receptor coding
scheme to encode odor identities: different odorants are
recognized, and thereby encoded, by different combinations of ORs,
but each OR serves as one component of the "receptor codes" for
many odorants. We found that a small change in odorant structure
can change its receptor code, thus providing an explanation for the
ability of such changes to alter perception. In recent studies, we
developed a genetic method for tracing neural circuits in
transgenic mice. We are now using this method to explore how
receptor codes are represented in the olfactory cortex.
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