Nature: Why are males reluctant to mate with sub-healthy females?

Click on the blue word to follow us, whether in conflict or cooperation, social activities of the same species are the basis for the survival and continuity of individuals and species.

In these social activities, mating behavior is the key social activity for reproduction of offspring and continuation of race genes.

However, performing wrong social activities may bring potential risks, such as infection of viruses and pathogens from a sick partner.

Studies have shown that female mice usually choose male mice that are not infected by parasites for mating.

On March 31, 2021, the Gloria B.
Choi research team of MIT's Picower Institute of Learning and Memory published an article in the journal Nature and found that male mice prefer the neural circuit that selects healthy female mice for mating.

Male mice are more willing to mate with healthy female mice.
Researchers paired male mice with female mice in estrus.
Before pairing, these female mice were injected with PBS solution (healthy female mice) or LPS solution ( LPS is lipopolysaccharide, which causes inflammatory reaction after intraperitoneal injection, hereinafter referred to as sick female mice).

The results showed that male mice prefer to mate with healthy female mice, and the latency of the first riding behavior with diseased female mice was prolonged, and the number and time of riding behavior were significantly reduced.

Simply put, male mice are reluctant to mate with sick female mice.

Animals can recognize the health status of their companions through the accessory olfactory system.

Therefore, after the researchers removed the chemoreceptor vomeronasal organ in male mice, the mating behavior with sick female mice increased.

In order to further find the key brain regions that regulate this inhibition of mating behavior, they screened through C-FOS.

The results showed that when contacted with sick female mice, male mice's accessory olfactory bulb, stria terminalis nucleus, COApm (posteromedial nucleus of the cortical amygdala) neurons were activated in large numbers, and COApm brain area neurons activated the most.

Fiber-optic calcium imaging technology records the calcium ion activity of neurons in the COApm brain area.
After injecting AAV-Syn-GCaMP6s into the COApm brain area, the researchers found through the fiber-optic recording system that compared with normal female mice, male mice were sniffing sick female mice.
During reproductive organs, the activity of calcium ions in neurons in this brain area was significantly enhanced, but during mating, the activity of neurons was decreased.

Small cloth practical Tips｜Calcium ion indicator selection & usage tips What’s more interesting is that the researchers applied the urine and feces of sick female mice to healthy adult female mice, and the male mice became reluctant.
Mate with these female mice with a "sick smell".

Light-activated COApm brain area inhibits the mating behavior of male mice.
Then the researchers injected activated optogenetic virus into the COApm brain area of ​​male mice, and found that the mating behavior with healthy female mice was significantly reduced, making the male mice become abnormal .

After chronically inhibiting neurons in this brain region of male mice, the mating behavior with sick female mice increased, but it did not affect mating behavior with healthy female mice.

These results indicate that this brain area plays a key role in the weak mating behavior of male mice and diseased female mice.

Light-activated COApm-MEA brain area causes neuronal changes.
In order to further find the main upstream target area of ​​the COApm brain area, the researchers injected an antegrade tracer virus into this brain area and found that most of the axons projected to the medial amygdala (MEA).
).

Further through fiber optic calcium imaging technology, it was found that after light-activated neurons in the COApm brain region, the calcium ion changes in the excitatory neurons in the MEA brain region were significantly stronger than those in the inhibitory neurons.

The mating behavior of male mice and healthy female mice was inhibited after light activated the COApm brain area to project to the axons of the MEA or activated the excitatory neurons in the MEA brain area alone.

Inhibiting excitatory neurons in the MEA brain region promotes the mating behavior of male mice and sick mice.

In addition, inhibiting COApm brain neurons alone does not affect the mating behavior with healthy female mice, but inhibiting the excitatory neurons in the MEA brain area can enhance the mating behavior of male mice and healthy female mice.

In order to further clarify the molecular characteristics of the excitatory neurons projected by COApm to the MEA brain area, the researchers performed single-cell sequencing of the above-mentioned neurons and found that the neurons of the neural circuit differentially express 1242 genes, of which neuroactive ligands -Receptor interaction pathway is the signal pathway with the most differential gene expression, including the thyroid stimulating hormone releasing hormone (TRH) gene.

TRH gene expression is mainly expressed in the COApm brain area, and its receptors are expressed on the excitatory neurons in the MEA brain area, which specifically activates TRH neurons in the COApm brain area or injects TRH receptor agonists into the MEA brain area.
Male mice are healthy The mating behavior of female mice is reduced.

This indicates that the TRH-TRH receptor signal mediates the COApm-MEA neural circuit to regulate mating behavior.

In summary, this article discovered the neural circuit that male mice are unwilling to mate with unhealthy female mice: COApm-MEA, and further revealed that TRH-TRH receptor signals are specifically expressed on this neural circuit.

[References] 1.
https://doi.
org/10.
1038/s41586-021-03413-6 The pictures in the article are all from the references