Risposte del calcio indotte da chetoni in neuroni olfattivi dell'orgao vomeronasale di topo.

Chemosensory systems (smell, taste) are distinguished from the other senses (e.g. vision, hearing, touch) by the high qualitative heterogeneity of the stimuli: the chemical senses are responsible for detecting molecules of immense chemical variety. A wide range of social chemosensory cues in the mouse are detected by olfactory and accessory/vomeronasal olfactory system. Social stimuli convey information about gender, identity, dominance, health status, and age. Some of these stimuli are able to trigger specific patterns of innate behaviors, or physiological changes, in the receiver and are hence known as ¿pheromones¿. The vomeronasal organ (VNO), a chemosensory organ which is found at the base of the nasal cavity, is the first stage of detection and processing of vomeronasal information. The VNO sensory epithelium contains bipolar receptor neurons, the vomeronasal sensory neurons (VSNs), which extend their dendrites, ending in a dendritic knob, in the vomeronasal lumen. There ¿ located on the surface of hundreds microvilli emerging from the knob ¿ receptor molecules known as vomeronasal receptors (VRs) interact with their ligands, which gain access to the organ lumen thanks to an autonomous-regulated mechanism of mechanical pumping. Within the mouse VNO, two distinct layers of VSNs are identifiable. They express different types of VRs (vomeronasal type-1 receptors, V1Rs, in the apical layer, and vomeronasal type-2 receptors, V2Rs, in the basal layer) and signalling cascade molecules, and synapse on distinguishable aspects of the accessory olfactory bulb (AOB), where second order neurons of the vomeronasal pathway are located. The specificities of these subsets of VSNs are not fully elucidated. Since most of the odorous and pheromonal stimuli which are known to be detected through the mouse VNO are represented by urinary components, we asked whether it was possible to assess a specificity in VSNs to acetone and ß-hydroxybutyrate, two molecules also known as ketone bodies (KBs), which are commonly found in urine. KBs are by-products of fatty acids metabolisms that are detectable in small amounts in blood and urine of mammals, and whose concentration rise in case of fasting, pregnancy or in metabolic diseases, such as type 1 diabetes (T1D). We hypothesize that the mice could detect information about conspecifics metabolic and health status (e.g. in order to choose an healthy partner for mating) by sensing urinary KBs via their vomeronasal pathway. Hence, we first tested if dissociated cells of the vomeronasal organ are able to detect these molecules using Ca2+ imaging experiments. A significant amount of vomeronasal dissociated cells (possibly VSNs) were found to respond to acetone and ß-hydroxybutyrate, suggesting that KBs detection could convey relevant information about conspecifics for reproductive aims. Beside Ca2+ imaging experiments, behavioural tests aimed at testing KBs detection and preference in vivo were performed. A clear pattern of detection was not demonstrated, but interesting data about female possible preference for urine over urine added with KBs were obtained.