The vomeronasal organ (VNO) is one of evolution's most direct enforcers. From its niche within the nose in most land-based vertebrates, it detects pheromones and triggers corresponding basic-instinct behaviors, from compulsive mating to male-on-male death matches. A new study from the Stowers Institute for Medical Research, published online in Nature Neuroscience on July 29, 2012, extends the scientific understanding of how pheromones activate the VNO, and has implications for sensory transduction experiments in other fields.
"We found two new ion channels-both of them potassium channels-through which VNO neurons are activated in mice," says Associate Investigator C. Ron Yu, Ph.D., senior author of the study. "This is quite unusual; potassium channels normally don't play a direct role in the activation of sensory neurons."
Humans have shrunken, seemingly vestigial VNOs, but still exhibit instinctive, pre-programmed behaviors relating to reproduction and aggression. Scientists hope that an understanding of how the VNO works in mice and other lower mammals will provide clues to how these innate behaviors are triggered in humans.
The VNO works in much the same way as the main olfactory organ that provides the sense of smell. Its neurons and their input stalks, known as dendrites, are studded with specialized receptors that can be activated by contact with specific messenger-chemicals called pheromones, found mostly in body fluids. When activated, VNO receptors cause adjacent ion channels to open or close allowing ions to flood into or out of a neuron. These inflows and outflows of electric charge create voltage surges that can activate a VNO neuron, so that it signals to the brain to turn on a specific behavior.
In 2002, as a postdoctoral researcher at Columbia University, Yu was a member of one of the first teams to find that VNO receptors rely heavily on a calcium channel called TRPC2. But there were hints that VNO neurons use other ion channels too; and in a study reported last November in Nature Communications, Yu's team at Stowers, including first author SangSeong Kim, Ph.D., a postdoctoral researcher, found evidence for the role of a chloride-specific channel, CACC.
In the new study, Yu, Kim and their colleagues looked for VNO potassium channels, which admit positively charged potassium ions. They began by setting up whole-cell patch clamp tests, in which tiny electrodes measure the net flow of charged ions through the membranes of neurons in a slice of mouse VNO tissue. To determine the contribution of potassium ions to these currents, they replaced the potassium ions in the neurons with chemically similar cesium ions, which cannot get through potassium channels. When these potassium-depleted VNO neurons were exposed to pheromone-containing mouse urine, the usual net inward flow of positive charge was significantly greater than it had been when the neurons contained potassium.