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Olfactory system detects pheromones that control reproduction

"One of the classical dogmas is that LHRH neurons receive inputs from the vomeronasal system. For example, textbooks on reproductive physiology say that pheromonal modulation of reproductive behavior depends on these connections," said Dulac. "However, our studies show that this idea is wrong."

Previous experiments designed to tease out the routes of neurons used techniques that depended heavily on dyes that could not label specific populations of neurons. These experiments suggested that neurons of the vomeronasal system are directly connected with LHRH neurons, and thus carry the modulatory effect of pheromonal cues on LHRH release. But because classical tracing techniques could not specifically identify the connection of neuronal subsets, they ended up tracing the routes of groups of undefined neuronal populations clustered around LHRH producing neurons, Dulac said.

In the experiments reported in Cell, Dulac and her colleagues used a genetically altered version of a pseudorabies virus that is a highly specific tracer, permitting the researchers to label neurons with a fluorescent protein marker. This technique relied on a conditional approach that caused the pseudorabies virus to replicate only when it was triggered by a specific genetic signal. The researchers also created a transgenic mouse in which neurons expressing LHRH provided that signal, making the viral tracer highly specific.

"So, whenever we saw a signal from the conditional virus, we knew we were seeing connections to neurons expressing LHRH and nothing else," said Dulac. As a control, the researchers also used a "non-conditional" strain of pseudorabies virus that infected all types of neurons.

The researchers chose pseudorabies virus for their studies because it could be introduced into a neuron and infect its way upstream along the network of axons that connect neurons. The virus could also jump the synapses between neurons, as it moved from one neuron to the ne
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Source:Howard Hughes Medical Institute


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