Sex and the single neuron: pheromones excite.

Pheromones are potent chemical signals used by animals across all phyla to control reproductive function and social behavior. Whereas there are few examples of the effects of pheromones on human behavior (fortunately?), in other species, such as laboratory mice, the effects of pheromones have been shown to be dramatic: a female mouse might abort a pregnancy if exposed to pheromones from a male mouse who is not her mate 1. In these animals, ablation experiments have shown that the vomeronasal organ (VNO), a chemosensory organ, which lies at the rostral end of the nasal cavity, plays a key role in pheromone detection. However, direct evidence for transduction of pheromones by VNO sensory neurons has been lacking, and even basic questions about sensory transduction remained controversial. For example, it was not known whether sensory neurons depolarize and fire action potentials in response to sensory stimuli, similar to olfactory sensory neurons, or whether they hyperpolarize, similar to vertebrate photoreceptors 2. The difficulty in detecting responses of VNO neurons to pheromones lies in the fact that the sensory cells are both heterogeneous in the receptors that they express and in their resulting ligand specificity. Thus identification of a cell that is responsive to a specific pheromone requires the ability to efficiently sample a large number of cells. This problem has now been overcome by two groups who have used different methodologies to record responses in populations of VNO neurons: in one case a 64-electrode multi-array 3 and in the other Ca 2+ imaging 4. Both groups developed methods to record from multiple cells, taking advantage of the unique anatomy of the VNO. The VNO is a tubular structure with a lumen down its length that communicates with the external environment and allows passage of chemical signals to the microvillous sensory endings of VNO neurons. In the approach taken by Leinders-Zufall et al. 4 , the VNO was cut in tranverse section, so that cells across all layers as well and their processes remained intact. As such, Ca 2+ transients in the cell body and in the dendrite and dendritic knob of sensory neurons could be imaged. In an alternative approach by Holy et al. 3 the VNO was cut longitudinally, so that the epithelial sheet could be flattened onto the surface of a 64-electrode microarray. In these experiments, electrical responses presumably originated from a subpopulation of neurons situated basally in the epithelium. Leinders-Zufall …