Marie-Christine Broillet group

Studies using gene-targeted mice have revealed the presence in the nasal cavity of multiple neuronal compartments. Indeed, in rodents, the detection of olfactory cues seems to be primarily mediated by chemosensory neurons localized in four distinct olfactory subsystems: the main olfactory epithelium (MOE), the septal organ (SO), the vomeronasal organ (VNO), and most rostral olfactory subsystem, the Grueneberg ganglion (GG). By activation of these olfactory subsystems, mice are able to decipher their environment and to display adequate behaviors. For example, pheromones that are molecules secreted from an animal that trigger a social response in conspecifics could activate specific neurons in the VNO and induce aggressive behaviors. Another relevant example is the case of alarm pheromones that are secreted in threatening situations and mediate, via the activation of GG neurons, fear-like reactions in the recipient animals. Interestingly, pharmacological components of the transduction cascades that take place in the different olfactory subsystems as well as in their internal neuronal subpopulations are different and diverse.
Our laboratory currently investigates chemosensory properties and signaling pathways in the VNO and in the GG focusing on the olfactory receptors that mediate key-lock interaction between the sensory neuron and the odorant molecule as well as on effectors such as the cyclic nucleotide-gated (CNG) channels that allow neuronal entry of calcium. Using complementary approaches such as transgenic mice models, molecular biology, cell cultures, chemical and histological imaging technics, we are particularly interested in the chemical identification of pheromones that mediate behavioral effects as well as in their neuronal pathways.

Figure 1: Calcium imaging experiment performed on acute tissue slice preparation on mice GG neurons. GG neurons are found between the nasal cavity (NC) and the nasal septum (NS). They are loaded with a ratio metric calcium dye, the Fura-2AM, here observed at 380 nm. Chemical responses in a GG neuron (black arrowhead) could be measured by the variation of the fluorescence level; here induced by a mouse alarm pheromone, the SBT or other chemically-related cues found in predator scents such as the TMT (red fox), DMP (bobcat) or 2-PT (stoat). (See Brechbühl et al., Frontiers in Neuroanatomy 8, p. 87, 2014)

Figure 2: Confocal acquisition of GG neurons in an OMP-GFP mouse. In red, a guanylyl cyclace GC-G immunohistostaining that allows the observation of GG cilia (white arrowheads), the potential localization of alarm pheromones detection. In green, the intrinsic GFP fluorescence observed in OMP-positive neurons. The merge view indicates the emergence of cilia from GG neurons in the non-neuronal tissue composing the nasal epithelia (counterstain with the nuclear staining, dapi). (See Moine and Brechbühl et al., Frontiers in Behavioral Neuroscience 7, p. 193, 2013)