Genetic dissection of olfactory inputs that mediate aversive responses.

• Applicant: Dr. Annika Cichy
• Subject Area: Cognitive, Systems and Behavioural Neurobiology
• Term: from 2014 to 2016
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 255453311

The ability to detect and discriminate myriad environmental chemicals and to translate that information into meaningful cellular responses is essential for the survival of all individuals. This challenge is met by different chemosensory systems. While the peripheral signal transduction mechanisms in the main olfactory systems have been extensively investigated, knowledge of the neural circuits underlying olfactory perception is still fragmentary.In the main olfactory epithelium, chemical cues are detected by three different classes of olfactory receptors: A large repertoire of canonical Class I and Class II odorant receptors and a much smaller repertoire of trace-amine associated receptors (TAARs). In the dorsal main olfactory bulb, these receptor classes are systematically mapped to glomeruli in three different sub-domains of the olfactory bulb. The reason for this methodic organization is unknown. It has been suggested that the domains in the olfactory bulb may relate to innate and learned odor responses by feeding into distinct hard-wired downstream circuits. The major goal of this new study is to shed light on the functional significance of this dorsal domain organization using the TAARs as model system. Most of the TAARs are mapped to glomeruli in a domain (DIII) that is selectively activated by structurally diverse amines. In addition, genetically deleting the TAARs results in abolishment of a specific, untrained behavior - aversion to amines. My hypothesis is that the dorsal TAAR inputs to the DIII domain couple to hard-wired circuits and function as a labeled-line to elicit aversion. To test this hypothesis, I will take advantage of several unique gene-targeted mouse strains to selectively activate TAAR inputs using optogenetics, and to specifically rewire TAAR inputs to different bulb domains. These strains will be analyzed using modern in-vivo imaging techniques, as well as behavioral assays. Together, my studies will allow me to assess, for the first time, whether amine aversion is innate, and whether it relates to receptor maps in the bulb. The expertise of Prof. Thomas Bozza and his lab, the unique tools and techniques they have established and the scientific environment at Northwestern University, all provide an exceptional foundation to successfully conduct this proposed new study.

• DFG Programme: Research Fellowships
• International Connection: USA
• Host: Professor Thomas Bozza, Ph.D.