The Bozza Lab

 

Volatile chemicals in the environment (odorants) are detected by olfactory sensory neurons in the nasal cavity. These sensory neurons respond to odorants and send signals directly to glomeruli in the olfactory bulb, the first region of the brain that processes olfactory information. Olfactory sensory neurons make specific axonal connections to the olfactory bulb, setting up a spatial representation of chemical information in the brain. We are interested in how this representation forms and how it contributes to encoding the stimulus. The lab is currently working on several projects.

 

 

 

Molecular organization of the olfactory map

Work from the lab has shown that the odorant receptor repertoire is broadly mapped on the surface of the olfactory bulb. Mammalian odorant receptors can be divided into three phylogenetically distinct classes (tree below), canonical Class I and Class II odorant receptors (green and red), and a small family of Trace Amine Associated Receptors, or TAARs (blue). We have discovered that all three classes of mammalian olfactory receptors are mapped to discrete projections in the dorsal olfactory bulb. We are currently determining how these projections form and how they function in sensory processing.

 

 

 

 

Contribution of single receptor genes and glomeruli to odor perception

Each receptor is represented by specific glomeruli in the mouse olfactory bulb. The glomerulus is considered a functional unit in olfactory processing. However, precisely how much each individual receptor and corresponding glomeruli contribute to odor perception is not well understood. We are taking a combined genetic, physiological and behavioral approach to address this question.

 

First, we are examining the consequences of activating specific glomeruli in awake behaving mice using optogenetics.

 

Second, we are genetically deleting single receptors, or groups of receptors, and looking at the effects on olfactory function.  In particular, we are looking at how individual receptors contribute to sensitivity.

 

These studies are allowing us for the first time to genetically dissect the contribution of specific olfactory functional units to sensory processing, and to relate chemical recognition at the molecular and perceptual levels.

Function of Trace Amine-Associated Receptors (TAARs) in mammals

The TAARs are a small, evolutionarily conserved family of GPCRs that act as

odorant receptors in the main olfactory system of mice and other mammals. How the TAARs contribute to olfactory function is not known. We are characterizing the function of TAARs using electrophysiological, imaging, and behavioral analyses in gene targeted mice. We have shown that these receptors are highly sensitive to amines and that a majority of the TAARs map to a subset of amine-selective glomeruli in the doral olfactory bulb (below and right). Using advanced mouse genetics, we have generated mice that lack all TAAR genes, or specific combinations of TAAR genes.

 

Our recent data demonstrate that mice normally display innate aversion to amines, but mice lacking the TAAR genes do not. In fact, deleting a single TAAR gene (TAAR4) specifically abolishes innate avoidance to phenylethylamine, a chemical that is enriched in the urine of carnivorous cats. TAAR4 may be specifically adapted to allow mice to detect and avoid carnivore urine scentmarks. We are investigating the circuits underlying this behavior, and whether the TAARs mediate behavioral responses to other ethologically relevant chemosensory stimuli.