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 system’s 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 person’s 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 Monell’s 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