My research interests revolve around a central theme: How does the brain control behavior?  I have, however, focused my research efforts on illuminating the mechanisms whereby one sensory system, the olfactory pathway, mediates behavior.  My research investigates this pathway at multiple levels by identifying olfactory cues that influence species-specific behavior, understanding how these cues are detected, specifying the brain regions which process signals initiated by these cues, understanding how internal physiology modulates these signals, and finally measuring the behavioral output triggered by these cues.  I use a combination of behavioral and anatomical techniques, in addition to newly acquired techniques such as electrophysiology and calcium imaging, to elucidate how the brain controls chemosensory mediated behaviors.

 

            My research program addresses fundamental behavioral and physiological questions at cellular, systems and behavioral levels. One avenue of investigation is addressing the relative roles of different olfactory systems for the processing and perception of chemosensory cues.  Within different vertebrate species there are as many as five separate chemosensory systems that potentially detect social cues including the main olfactory system, accessory olfactory system, trigeminal nerve, septal organ and the nervous terminalis. Of these five, the vast majority of odor cues are detected by either the main olfactory system or the accessory olfactory system. The reigning dogma has been that pheromones and other socially relevant chemosensory cues are detected by the accessory olfactory system whereas "normal" odorants are detected by the main olfactory system. As a number of researchers, including myself, have now shown this simple dichotomy is no longer tenable.  Thus, much of my research is aimed at describing the relative roles of these two complementary, yet distinct chemosensory systems capable of mediating social behaviors.   I am currently am working on two different projects which are exploring this topic.

 

First, I am studying the role(s) of the main and accessory olfactory systems in mediating appetitive social behaviors in mice, a line of investigation that is supported by an R03 Grant awarded to me from the NIDCD.  In these studies, I am utilizing mice with targeted deletions of genes critical for signal transduction in either olfactory or vomeronasal sensory neurons. Mice with a deletion of the transient receptor potential channel subunit 2 (TRP2) have strongly impaired pheromone responses in the vomeronasal organ, while mice with a targeted deletion of the cyclic nucleotide gated channel subunit 2 (CNGA2) exhibit no odor responses in olfactory receptor neurons. Using these two lines of mice as models, I am examining how the two olfactory systems interact to control social behavior. One of the unique features of my behavioral research program is that I use a combination of both preference and operant discrimination behavioral tasks. Using both of these types of tasks makes it possible to differentiate between discrimination of and motivation for biologically relevant chemosensory stimuli.  Differentiating discrimination from motivation is of critical importance since understanding motivation is the key to revealing how chemosensory cues control social behavior.  In addition to various behavioral tasks, I will use anatomical markers of neuronal activation such as c-fos immunocytochemistry to explore functional activation of each of these sensory systems in the absence of its counterpart.

 

            A second line of research that I am currently undertaking on this topic includes the study of major histocompatibility complex (MHC) related odors, and how these odors may pass along information of genetic individuality using both the main and accessory olfactory systems. MHC genes, which in the immune system are responsible for signaling self vs. non-self recognition of cells, also convey genetic individuality through chemosignals present in biological fluids. I am currently investigating MHC class I peptides ligands, which can be excreted in urine, by analyzing the mechanisms that underlie detection of these chemical cues.  To this end we are using a combination of electrophysiological techniques, recording field potentials in the main olfactory epithelium, and behavioral tasks, such as recognition and preference tests. In addition we are using both CNGA2-KO and TRPC2-KO mice to understand which olfactory system(s) (main vs. accessory) are necessary for detection and processing of MHC related odors in the context of each behavior. Interestingly, It appears that both the main and accessory olfactory systems are capable of detecting MHC related odors but may be responsible for mediating different aspects of individual recognition.