Alpha male pheromones stimulate neurogenesis in the female brain

Females have a natural preference for mating with dominant males, because this confers a genetic advantage upon the offspring produced. When selecting a mate, animals rely on chemical cues called pheromones, which relay information about the social status and genetic health of a potential mate.

Reproductive success therefore depends upon the encoding and recall of olfactory memories; the neural circuitry in which these memories are formed consists of the olfactory bulb and the dentate gyrus of the hippocampus. But although both these sites are principle regions for neurogenesis (formation of new nerve cells), few researchers have investigated their role in pheromone-dependent mating behaviour.

Now, a new study published in Nature Neuroscience demonstrates that pheromones from dominant male mice elicit hormonal changes in the brains of females that stimulate neurogenesis in the olfactory bulb and the parts of the brain encoding olfactory memories, and that the newly-generated cells may have a role in mating behaviour.

Although newly-generated neurons migrating into the olfactory bulb or dentate gyrus are known to become integrated into the existing circuitry there, the function of these new cells has until now remained unclear.

The new findings show that the cells generated in response to alpha male pheromones are involved in encoding memories of the pheromone signatures that are essential for the selection of an appropriate mate.

Mak, et al exposed adult female mice to various odours by soiling the bedding in their cages with coconut, almond or male urine (which contains pheromones), and renewed the bedding every two days for either 2 or 7 days. 

To determine the extent of cell proliferation in the olfactory bulb and dentate gyrus, the mice were injected with bromodeoyxuridine (BrdU, a chemical that is integrated into newly-synthesized DNA); their brains were then dissected and stained with an anti-BrdU antibody. The tissues were also stained with a molecular marker for immature neurons.

There was no significant increase in neurogenesis in females exposed to the coconut or almond odours, or in those exposed to the urine of a dominant male for 2 days. Nor was there an increase in animals exposed to the urine of castrated males, which lack testosterone and therefore do not secrete pheromones in their urine.

But in those animals exposed to the urine for 7 days, there were significantly more cells labelled with BrdU in both the dentate gyrus of the hippocampus and the subventricular zone (SVZ, the proliferative lining of the lateral ventricles were new cells are formed before migrating through the rostral migratory stream to the olfactory bulb). 

Those females exposed to the urine for 7 days showed a strong preference for dominant males over subordinate ones. On the other hand, those exposed to the coconut or almond odours, or to male urine for just 2 days, showed no such preference.

These findings suggest that the pheromones in the urine of dominant males are stimulating neurogenesis, and the cells generated in response to the pheromones are involved in encoding the scent of the dominant male. If this is the case, then the newly-generated cells must be essential for mate selection in the female. 

To test this, the researchers used a chemical called cytosine arabinoside to inhibit neurogenesis in females that had been exposed to urine for 7 days. These mice subsequently showed no preference for dominant over subordinate males.

Then, the researchers destroyed the olfactory system of females using an intranasal injection of zinc sulphate before exposing them to urine from a dominant male. This compound abolishes the response of females to male urine and decreases their sniffing behaviour; and, as expected, they no longer had a preference for dominant over subordinate males.

The researchers also found that pheromone-stimulated neurogenesis is mediated by hormones. Prolactin was found to stimulate the formation of new cells in the SVZ/ olfactory bulb, while luteinizing hormone stimulated neurogenesis in the dentate gyrus.

This was confirmed by the observation that exposure to urine from a dominant male did not stimulate neurogenesis in the olfactory bulb of females lacking the gene encoding the prolactin receptor, or in the dentate gyrus of females lacking the gene gene encoding the luteinizing hormone receptor.

So this study provides a model whereby male rodent pheromones stimulate the generation of new cells in the female brain; the cells generated in response to the pheromones are essential in encoding the odours of the dominant male.

According to this model, the male pheromones activate receptors in the olfactory epithelium of the female, which signal the hypothalamus to release prolactin and luteinizing hormone. These hormones then stimulate neurogenesis in the olfactory bulb and dentate gyrus, respectively, and the newly-formed cells determine the female's preference for mating with a dominant male.

Male urine contains a mixture of pheromones, and it is not yet clear exactly which chemical - or chemicals - stimulated neurogenesis in these experiments. Nevertheless, the findings establish a possible role for newly-formed cells in the adult mammalian brain.

Researchers discovered putative human pheromone receptors last year, so naturally, these findings make one wonder about the role of pheromones in human mating behaviour. They will, of course, be of great interest to those working in the perfume industry, which is worth more than $10 billion per year.

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Could there be visual pheromones, as in representational archytpes via known experience through image and text behaviors. cause if i look like a depressed poor loser on an online dating site then stupid women (all of them) dont want me, even if i show my innate conceptual wit, they are territorial monkeys despite all of the fake make up.

Researchers discovered putative human pheromone receptors last year...

That posting happens to be exactly one year old. Has there been any significant follow-up?

By Pierce R. Butler (not verified) on 31 Jul 2007 #permalink

How could a development of such great theoretical & practicable importance not have had enough interest that it wouldn't have labs competing over it in 12 months?

My (totally lay) impression is that once that set of six TAAR genes have been identified as shared between mice & humans, various developmental pathways could be tentatively modeled quite rapidly, no?

Probably demonstrating my laitude: last I heard, no human analog of the vomeronasal receptor or other pheromone intake system had been found - T or F?

By Pierce R. Butler (not verified) on 01 Aug 2007 #permalink

The vomeronasal organ (VNO) is known to exist in human embryos, but I think its existence in adults is still disputed.

Must remember to expose more females to my urine.