Olfactory subsystem. The mouse has at least three olfactory sensory organs: the main olfactory epithelium (MOE), the vomeronasal organ (VNO) and the Grueneberg ganglion (GG). Sensory neurons projection to the main or accessory olfactory bulb (MOB, AOB). GC-D neurons (inset, white cell) lie within the MOE and project to the necklace glomeruli (NG).

Genetic dissection of an olfactory subsystem. GC-D neurons and their projections to the necklace glomeruli (blue) in the MOB can be visualized using genetically-encoded reporters.

Olfactory detection of social cues

It has become increasingly clear that the concept of a single olfactory system is grossly oversimplified. The olfactory system is actually composed of a number of subsystems, some well known and others only recently characterized. These subsystems may be anatomically segregated within the nasal cavity, and they each make distinct neural connections to regions of the olfactory forebrain. They are clearly distinguished by the receptors they express and the signaling mechanisms they employ to detect and transduce chemosensory stimuli, and they respond to a plethora of diverse molecules, sometimes quite specifically, that range from volatile odors to peptides and proteins. We are using integrative approaches in the mouse to decipher the transduction mechanisms of these specialized subsystems, the ways in which the forebrain processes these signals, and the specific behaviors that they mediate. Of particular interest is the GC-D/necklace subsystem, which is specialized to detect chemosignals that facilitate food-related social learning. Ongoing efforts are geared to understanding whether this system can be harnessed to promote the ingestion of specific edibles in the context of pest control and animal feeding.

The molecular diversity of taste cells. Sensory cells in the mouse taste bud labeled for different signaling molecules.

Extraoral chemoreceptors and the regulation of metabolism

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The T1R and T2R families of G protein-coupled receptors play critical roles in the taste system, where they mediate the detection of sweet, savory and bitter-tasting stimuli. However, in recent years it has become clear that these same receptors are expressed in numerous tissues throughout the body. Some of these extraoral “taste” receptors may facilitate metabolic responses to ingested nutrients, while others may protect the body from inhaled or ingested toxins. Currently, we are using in vivo and in vitro approaches to characterize the roles of these two receptor families in the detection of chemostimuli by endocrine cells of the gut, pancreas and thyroid. These studies should offer important new insights into the molecular and cellular mechanisms underlying metabolic diseases such as obesity, Type 2 diabetes mellitus, the metabolic syndrome and thyroid dysregulation.

Odors, pheromones and taste stimuli contain important information about the quality and nutrient content of food, the suitability of mates, and the presence of predators or competitors. To detect these diverse chemical cues animals employ several distinct populations of chemosensory cells in the nose, mouth and gut, each of which expresses specialized receptors, channels and transduction cascades, though the physiological consequences of this molecular diversity remain poorly understood. In our lab we are working to understand how diverse chemosensory transduction mechanisms, including different taste and olfactory receptors, contribute to chemosensory function, impact ingestive and social behaviors, and interact with hormonal systems that regulate metabolism, nutrient response and homeostasis. Current areas of research include:

Mechanisms of alimentary chemosensation

We are investigating the interactions between taste and hormonal systems. A key function of the taste system is to detect nutrients, toxins and indicators of spoilage, thus providing the animal with critical information about the quality and nutritional value of food before it is ingested. The ability to detect and discriminate taste stimuli is essential for health and survival, and can drive ingestive behaviors. Therefore, physiological mechanisms that modulate taste function in the context of nutritional needs and metabolic status could optimize ingestive decisions and directly impact human health. Although the gustatory system critically influences food preference, food intake and metabolic homeostasis, the physiological mechanisms that link taste function and metabolism are poorly understood. Recent findings from our laboratory and others suggest that the gustatory and gastrointestinal systems utilize a common molecular toolkit of receptors, signaling molecules and hormones to detect nutrients and other chemicals. This is consistent with a role for taste function in the maintenance of metabolic homeostasis and suggests that sensory function may be modulated in the context of metabolic status.

Taste receptors. Type 1 taste receptors (T1Rs, red and blue) function as heterodimeric receptors for sweet (T1R2+T1R3) or umami (T1R1+T1R3) stimuli. Type 2 taste receptors (T2Rs, green) respond to bitter-tasting stimuli. Both families of receptors are members of the G protein-coupled receptor (GPCR) superfamily.