NEUROSCIENCE AND
MOLECULAR BIOLOGY
Perception of tastes, odors and chemical irritants begins with the
interaction of a chemical stimulus with specialized sensory receptor cells in
the mouth, nose and skin. A cascade of molecular and cellular events transduces
information about the stimulus into electrical signals recognized by the
nervous system. A combination of approaches biochemical, biophysical,
neurophysiological, molecular biological, and genetic is being used to
characterize how chemical stimuli are recognized, transduced into electrical
signals in receptor cells, and processed in the brain. Recent advances in
molecular genetics are helping researchers to describe how genes influence the
chemical senses, from olfactory receptor function to sensitivity to different
tastes. Taste responses to foods and beverages are mediated by
receptor cells located in taste buds scattered over the tongue, palate, and
throat. In the receptor cells, taste stimuli activate pathways that ultimately
result in the release of neurotransmitter, which acts to change the activity of
adjoining nerve fibers carrying signals to the brain. Studies at Monell
indicate that taste responses may be modulated and shaped by interactions among
cells within a single taste bud. These interactions provide the basis for
significant processing of taste information even before the signals reach the
brain. Biochemical and biophysical studies are exploring the mechanisms that
generate taste signals in the receptor cells, while molecular biological and
molecular genetic techniques are being used to identify taste receptor
proteins, ion channels, and components of the cellular second messenger
pathways involved in generating taste responses.
The nose
contains millions of receptor cells, which mediate the olfactory systems
high sensitivity to an extraordinary range of odors. Olfactory receptors cells
are nerve cells which communicate directly with the brain. Inside the nose,
odorant molecules interact with receptor proteins located in cilia extending
from exposed ends of the receptor cells. This activates the formation of
so-called second messengers, that modulate passage of ions through
channels in the cell membrane, in turn generating nerve impulses that are
transmitted directly to the olfactory bulbs.
Monell
scientists are involved in characterizing these second messenger pathways and
how they are coupled to the generation of neural signals. Cyclic
3,5 adenosine monophosphate (cyclic AMP) is well-established as a
second messenger in olfactory responses in mammals. Another second messenger,
inositol 1,4,5-trisphosphate (IP3), has also been implicated in mediating
olfactory responses to some odorants. Recent work at the Center indicates that
these two pathways may interact within the same receptor neurons. Other studies
are characterizing the neural circuitry involved in transmission and processing
of olfactory signals in the olfactory bulbs.
Chemosensory
irritation and pain serve as a warning system for damaging substances.
Sensations of irritation, including pungency, cooling, itch and tingle, signal
the presence of potentially harmful conditions. Monell scientists are
furthering our understanding of the organization and function of the nerves
that mediate irritating sensations in the mouth.
With the recent discovery of genes involved in bitter taste and the
sequencing of the entire human genome, scientists can now examine genes at the
nucleotide level and correlate differences in DNA with a persons taste
sensitivity. Molecular genetics studies focus on the genetic basis of
individual differences in taste and nutritional status. Center scientists are
currently characterizing genes important in bitter and sweet taste, as well as
genes that influence obesity and the preference for dietary fat.
Ongoing
studies in Monells Neuroscience and Molecular Biology program include
studies designed to:
- Characterize the pathways that mediate taste cell responses to
different stimuli and their distribution among receptor cells
- Uncover the
molecular and cellular bases of genetic differences in sensitivity of different
strains of mice to taste stimuli
- Characterize the responses of olfactory and taste receptor cells
isolated from human volunteers
- Identify
changes in olfactory sensitivity and receptor cell function in elderly
volunteers and Alzheimer disease patients
- Determine
the genetic basis of individual differences in taste and nutritional
status
- Clarify
receptor and transduction processes for umami taste
- Use
computational models to predict the transport and deposition of odorants
through the nasal cavity
- Determine
how growth-promoting substances in the brain help determine the structural
organization and health of olfactory system neurons
- Identify
the thresholds for activation of sensory neurons by various noxious
compounds
- Develop
cell culture systems to study chemosensory neurons under controlled
conditions
- Use the
distribution of olfactory receptors for different qualities on individual
receptor neurons to unravel olfactory coding
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