A new mouse study shows how different brain circuits for males and females turn chemical signals into either aggressive or sexual behavior, respectively.

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A new study in mice brings us closer to understanding how pheromones may enhance sexual behavior in humans.

Many of us have heard about pheromones making some people seem more attractive than others, but little is known about the exact mechanism that makes this possible.

In animals, sense of smell plays a key role in regulating instinctive responses, and whether or not they react to competitors, predators, or potential mates.

A team of researchers led by Kazushige Touhara, a professor at the University of Tokyo’s Graduate School of Agricultural and Life Sciences in Japan, set out to examine how male pheromones enhance sexual behavior in female mice.

Prof. Touhara explains, “It is widely known that some chemicals, especially odors, can impact an animal’s instinctive behaviors even on first contact. We assumed there was a neural mechanism in the brain that correctly connects important sensory information to appropriate behavioral centers in the brain.”

A look at the sexual behaviour of mice, our fellow mammals, can bring valuable insights into human reproductive behavior. The findings were published in the journal Neuron.

Prof. Touhara and team examined a male pheromone called exocrine gland-secreting peptide 1 (ESP1), which has been shown in previous studies – referenced by the authors – to drive sexual behavior in female mice and aggressive behavior in male mice.

ESP1 is different from other pheromones because it is a single chemical that corresponds to a single receptor, making it easier for the researchers to track.

To do so, the scientists infected the ESP1 receptor neurons with a virus. Once the virus had spread, the scientists marked the infected brain cells with a fluorescent protein, so that they could see the neural circuit taken by the ESP1.

In other words, the researchers were able to see how ESP1 signals are conveyed in the brain, as neurons send electrical impulses to other neurons through the synapses.

Using this fluorescent viral tracing method, Prof. Touhara and team saw that the circuit taken by the ESP1 signal in the amygdala differed between males and females. The amygdala was shown to contain another subarea that acted as a “switch,” relaying ESP1 information to different parts of the hypothalamus depending on the mouse’s sex.

The amygdala is the part of the brain’s limbic system, which deals with emotions, emotional behavior, and motivation.

The researchers mapped how the “ESP1 information is conveyed from the peripheral receptive organ to the motor-regulating midbrain via the amygdala-hypothalamus axis.”

In females, sexual behavior was modulated by a newly discovered pathway from the hypothalamus to the midbrain.

The hypothalamus is the brain area responsible for releasing hormones that regulate a variety of bodily functions, including body temperature, appetite, sex drive, thirst, sleep, and mood.

The study also revealed that activating the ESP1 receptor neurons in the brain’s hypothalamus boosted sexual activity in female mice, even when actual ESP1 was not present.

Additionally, the researchers tested the response of receptor neurons to snake skin in the same brain area – more specifically, in the brain’s dorsal ventromedial hypothalamus, which is a region associated with defensive behavior. Snake skin is a predator cue signal for mice, which makes them act aggressively in defense.

The scientists found no change in sexual behavior after activating the neurons that responded to the predator cue signals.

“This finding suggests that there are two different types of neurons, ESP1 and predator neurons, and only the former controls sexual behaviors in female mice,” Prof. Touhara explains.

The authors note that more research is needed to better understand how female sexual behavior works, as well as how it can be regulated. Specifically, researchers could obtain a strategy for turning male pheromones into a sexual response from the females. This may provide valuable insight into how sexual dysfunctions arise.

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