For decades, it was thought that while the brain orchestrated male sexual behavior-excitement, cutting and copulation-the spinal cord only performed the final act: ejaculation. A Champalimaud Foundation study challenges this division of functions.
A new study reveals a spinal circuit key that is not only involved in ejaculation, but also in excitement and in the orchestration of sex choreography, adding a new and surprising dimension to our understanding of the sexual behavior of mammals.
The results of the, conducted by a team of researchers from the Champalimaud Foundation (FC), were presented in an article published this Tuesday magazine Nature Communications.
“The spinal cord It’s not just a relay station passive that executes the commands of the brain, ”says Susana Limamain researcher at the FC Neuroetology Laboratory and the study’s senior author.
“She integrates sensory stimuliresponds to excitement and adjusts your response based on the animal’s inner state. It is much more sophisticated than we imagined, ”adds the researcher in a statement published in.
The neurons that move the engines
“Initially, we were interested in female sexual behavior,” recalls Lima, “but It is difficult to identify the moment of orgasm in females. In males, ejaculation is a clear and observable marker-can literally be seen in muscle activity. ”
The team departed from a seemingly simple question: What are the neurons that control the muscle responsible for ejaculation?
“The muscle in question is the bulboesponious muscleor MBE, ”explains the first author of the study, Constanze LenschowGroup leader at the Institute Initia of the University of Bordeaux. “It is just below the penis and is critical to the expulsion of sperm. When the male ejacula, the MBE shoots in a characteristic discharge pattern. It is the signing of ejaculation”.
To reassemble to the origins of this sign, the team used anatomical mapping techniques to follow the route from MBE to their motor neurons – that is, to the cells that directly command their contraction.
Then the investigators took another step, looking for the neurons that control the motor neurons. Initial attempts to map nerve connections using a rabies virus marker did not result.
“It was frustrating”Says the co -author Ana Rita Mendeswho joined the project during his master’s degree. “So we had to change tactics”.
Previous studies in the rat had identified a group of spinal cord neurons that express a molecule called gahanna (Gal), fundamental for ejaculation.
Based on these results, the team used genetically modified mice in which neurons expressing Gal (designated Gal⁺) Red red.
To the microscope, the researchers thus managed to see that the axons of the Gal⁺ neurons – the long fibers that transmit the nerve signs – if overcame to MBE motor neuronssuggesting a direct excitatory connection.
To test this connection, Lenschow used a electrophysiological techniquecalled Patch-Clamp, in slices of the spinal cord.
“When we activated the distal ends of the Gal⁺ neurons – the places where they transmit their signs – We registered an explosion of activity in the motor neurons of the MBE. And when we blocked glutamate – the chemical these neurons use to excite other neurons – the signal has disappeared, confirming a direct excitatory connection, ”the researchers explain.
It was the first time that a functional connection, from one-to-onebetween spinal neurons Gal⁺ and motor neurons that control ejaculation, was demonstrated. “And curiously,” says Mendes, “the Gal⁺ neurons did not only project the muscle of ejaculation, but also binded to other areas involved in erection and autonomous control of ejaculation. ”
It is also important to highlight that the team demonstrated that the Gal⁺ neurons receive sensory stimuli from the penis.
In mice with the sectioned spinal cord – and therefore separated from the brain – a slight breath of air in the penis activated both the Gal⁺ neurons and the MBE motor neurons, confirming that the circuit is sensitive to genital stimulation.
Neuroethology Lab / Champalimaud Foundation
Cross section of the spinal cord showing neurons involved in ejaculation. Pink-marked cells (neurons that express galanine) overlap with green (a sign of recent activity), revealing that these neurons are active during ejaculation. Blue marks all nerve cells as a visual guide.
Stimulating the sexual circuit
To test if these Gal⁺ neurons could actually cause ejaculation, the team used the electrical stimulationas well as a more accurate method, called optogenetics, which allowed them to activate selectively, using light, the Gal⁺ neurons in genetically modified mice.
In Ratzana, the stimulation of these neurons triggered ejaculation consistently. But In the mouse, things did not run as expected.
“We managed to activate the MBE, but the stimulation of Gal⁺ neurons never led to true ejaculation,” says Lenschow. “And unlike the rats, when we repeat the stimulation of the Gal⁺ cells, the MBE answers weakened. as if the system entered a refractory state after initial activation. ”
Note that the robust activity of MBE only occurred in the mice whose spinal cord had been sectioned, removing brain inputs. This suggests that the descendants of the brain actively suppress the spinal circuit – until the right time.
“Our findings support a model in which the descendant input – probably coming from a region of the brain trunk – inhibits the Gal⁺ neurons and the signs coming from the genitals until the animal reaches the ejaculatory threshold”Says Mendes.
Together, the results suggest that Gal⁺ neurons receive sensory stimuli, They weigh the internal and external signals and start the motor standard that ends in ejaculation – and that your involvement ends there. But there was still one more unexpected element to find out.
“If the mouse had already ejaculated, the stimulation of Gal⁺ neurons did not work: MBE simply didn’t respond”Says Lenschow.” This suggests that Gal⁺ neurons are not only coordinating ejaculation, but also to integrate the internal state of the animal. “
In other words, The spinal cord seems to “know” Whether the mouse has ejaculated recently or not. “This is a level of contextual sensitivity that we do not normally associate with spinal circuits,” adds Mendes.
Ratinhos and men: a better correspondence than with the Ratzanas?
The researchers were asked then: what happens if we use a toxin directed to selectively eliminate the Gal⁺ neurons in mice during sexual behavior?
“In RATAZANA, the destruction of these cells completely blocks ejaculationBut the copulatory standards leaves intact, ”explains Mendes.
“In the mouse, however, the effect was more subtle. Only three in 12 males were unable to ejaculate, and many showed a disturbance of the copulatory sequence: had difficulty finding the vagina And it took longer to ejacular after a larger number of frustrated attempts, ”he adds.
This pointed to a sensory deficitsuggesting that Gal⁺ neurons in healthy mice integrate mechanical touch or feedback, and influence the arousal and rhythm of sexual behavior.
“The spinal neurons gal⁺ seem to perform a different role in the mice, ”says Lenschow.“ That probably reflects own strategies of the kind of structuring and programming of the sexual act ”.
In the rats, ejaculation is more like a reflection – Genital stimulation is often sufficient to trigger it, sometimes during the first one. The mice, on the contrary, are involved in repeated mounds and invested before ejaculation, which resembles the gradual increase in excitement observed in humans.
“Ratzanas can be good models to study premature ejaculation,” says Lenschow, “but mice can actually be a better animal model to understand how human sexuality works, how excitement increases and how ejaculation is regulated.”
A multidirectional dialogue
These results challenge the traditional view of sexual control, from top to bottom, and lead to rethink the way ejaculation is controlled.
Instead of the brain simply has the spinal cord acts, the two seem to be in continuous dialogue – With the spinal neurons Gal⁺ receiving sensory information, modulating the motor response and integrating signs related to the animal’s excitement and internal state.
Spinal integration may even contribute to the refractory period – the temporary decrease in sexual response after ejaculation, suggesting that the spinal cord itself helps to control the readiness of the system to function again, contrary to what has been thought so far.
“We think of the spinal cord like a kind of crossroads”Says Lima,“ which integrates the stimuli of the genitals, prostate and brain, helps to orchestrate the sequence and timing of the copulation and to determine if the conditions are suitable for ejaculation. ”
In fact, Lima speculates that “point of no return” – The moment after which ejaculation becomes inevitable – may not come from the brain, but from the prostateacting as an internal state update: “I’m ready. Time to move forward.”
In addition to fundamental biology, these findings open new ways to understand sexual dysfunction and erectile disorders.
