Cross-section of spinal twine displaying neurons concerned in ejaculation. Cells marked in pink (galanin-expressing neurons) overlap with these in inexperienced (a sign of latest exercise), revealing that these neurons are lively throughout ejaculation. Blue marks all nerve cells as a visible information. Credit score: Neuroethology Lab, Champalimaud Basis
For many years, it was thought that whereas the mind orchestrated male sexual conduct—arousal, courtship, and copulation—the spinal twine merely executed the ultimate act: ejaculation. However a research from the Champalimaud Basis (CF) challenges that tidy division. It reveals {that a} key spinal circuit just isn’t solely concerned in ejaculation but in addition in arousal and shaping the choreography of intercourse, including a stunning new dimension to our understanding of sexual conduct in mammals.
“The spinal cord isn’t just a passive relay station executing brain commands,” says Susana Lima, Principal Investigator of CF’s Neuroethology Lab and senior creator of the research. “It integrates sensory inputs, responds to arousal, and adjusts its output based on the animal’s internal state. It’s much more sophisticated than we imagined.”
The work is printed in Nature Communications.
The neurons that drive the drivers
“We were initially interested in female sexual behavior,” remembers Lima, “but it is difficult to pinpoint the moment of orgasm. In males, ejaculation is a clear and observable marker—you can literally see it in the muscle activity.” The crew started with a deceptively easy query: which neurons management the muscle liable for ejaculation?
“The muscle in question is the bulbospongiosus, or BSM,” explains Constanze Lenschow, co-lead creator and now Group Chief on the INCIA Institute on the College of Bordeaux. “It sits just below the penis, and is critical for sperm expulsion. When a male ejaculates, the BSM fires in a characteristic burst pattern. It’s like the signature of ejaculation.”
To hint the origins of this sign, the crew used anatomical tracing methods to map the pathway from the BSM again to its motor neurons, the cells that straight command it to contract. They then seemed one step additional: which neurons management these motor neurons? Preliminary makes an attempt to map connections utilizing a rabies virus tracer hit a wall.
“It was frustrating,” says co-first creator Ana Rita Mendes, who joined the undertaking throughout her MSc. “So we switched tactics.”
Earlier work in rats had recognized a bunch of spinal neurons expressing a molecule referred to as galanin (Gal) as key to ejaculation. Constructing on this, the crew used genetically modified mice by which Gal-expressing (Gal⁺) neurons fluoresced purple. Beneath the microscope, they noticed that the axons—lengthy projections that transmit alerts—of those Gal⁺ neurons overlapped with the BSM motor neurons, suggesting a direct hyperlink.
To check this, Lenschow carried out patch-clamp electrophysiology in spinal twine slices. “When we activated the far ends of Gal⁺ neurons—where they pass on signals—we recorded a burst of activity in the BSM motor neurons. And when we blocked glutamate—the chemical these neurons use to excite others—the signal disappeared, confirming a direct, excitatory connection.”
This was the primary time a purposeful, one-to-one connection between Gal⁺ spinal neurons and ejaculation-controlling motor neurons had been demonstrated in any species. “And interestingly,” notes Mendes, “Gal⁺ neurons didn’t just project to the ejaculation muscle, they also connected to other areas involved in erection and the autonomic control of ejaculation.”
Importantly, the crew confirmed that Gal⁺ neurons obtain sensory enter from the penis. In spinalized mice—the place the spinal twine is severed from the mind—a light-weight puff of air to the penis activated each Gal⁺ neurons and BSM motor neurons, confirming that the circuit is delicate to genital stimulation.
Turning on the intercourse circuit
To check whether or not these Gal⁺ neurons might really drive ejaculation, the crew used both electrical stimulation or a extra exact technique referred to as optogenetics, which enabled them to selectively activate Gal⁺ neurons in genetically modified mice utilizing gentle.
In rats, stimulating these neurons reliably triggers ejaculation. However in mice, issues did not go as anticipated. “We could get the BSM to fire, but stimulation of Gal⁺ neurons never led to a real ejaculation,” says Lenschow. “And unlike in rats, when we repeated Gal⁺ stimulation, BSM responses weakened. It was as if the system had entered a refractory state after that initial activation.”
Notably, sturdy BSM exercise solely occurred in spinalized mice, the place mind enter was eliminated. This implies that descending alerts from the mind actively suppress the spinal circuit—till the best second. “Our findings support a model where descending input—likely from a brainstem region—inhibits the Gal⁺ neurons and incoming genital signals until the animal reaches the ejaculatory threshold,” says Mendes.
Taken collectively, the outcomes recommend that Gal⁺ neurons obtain sensory enter, weigh inside and exterior alerts, provoke the motor sample that ends in ejaculation—after which step apart. However there was yet another twist.
“If the mouse had already ejaculated, Gal⁺ stimulation didn’t work—the BSM just wouldn’t respond,” says Lenschow. “That told us these neurons weren’t just coordinating ejaculation. They were integrating the animal’s internal state.” In different phrases, the spinal twine appeared to “know” whether or not or not the mouse had just lately ejaculated. “That’s a level of context sensitivity we don’t typically associate with spinal circuits,” provides Mendes.
Of mice and males: A greater match than rats?
The researchers then requested: what occurs if we use a focused toxin to selectively remove Gal⁺ neurons in stay mice?
“In rats, destroying these cells completely blocks ejaculation—but leaves copulatory patterns intact,” explains Mendes. “In mice, however, the effect was more subtle. Only 3 out of 12 males failed to ejaculate, and many showed a disrupted sequence: they struggled to find the vagina, and took longer to ejaculate, with more failed mounts and probing attempts.”
This pointed to a sensory deficit, suggesting that Gal⁺ neurons in wholesome mice combine contact or mechanical suggestions, in addition to affect arousal and the pacing of sexual conduct. “Gal⁺ spinal neurons seem to play a different role in mice,” says Lenschow. “It likely reflects species-specific strategies for how sex is structured and timed.”
In rats, ejaculation is extra like a reflex—genital stimulation is commonly sufficient to set off it, generally in the course of the first mount. Mice, against this, interact in repeated mounts and thrusts earlier than ejaculation, resembling the gradual build-up seen in people.
“Rats may be good models for studying premature ejaculation,” notes Lenschow, “but mice might actually be better for understanding how human sexuality works—how arousal builds, and how ejaculation is regulated.”
A multiway dialogue
These findings problem the standard top-down view of sexual management and result in a rethinking of how ejaculation is managed. As an alternative of the mind merely commanding the spinal twine to behave, the 2 seem like in steady dialogue—with the Gal⁺ spinal neurons receiving sensory enter, modulating motor output, and integrating alerts associated to arousal and inside state.
This spinal integration might even contribute to the refractory interval, the non permanent lull in sexual responsiveness after ejaculation, suggesting that the spinal twine itself helps management when the system is able to go once more, opposite to present considering.
“We think of the spinal cord as a kind of crossroads,” says Lima. “It integrates input from the genitals, the prostate, and the brain, and helps orchestrate the sequence and timing of copulation and determine whether conditions are right for ejaculation.”
In reality, Lima speculates that the “point of no return”—the second after which ejaculation is inevitable—might not come from the mind in any respect, however from the prostate, performing like an inside standing replace: “I’m ready. Time to go.”
Past primary biology, these findings open new avenues for understanding sexual dysfunction and erectile problems. The crew’s subsequent step is to report straight from Gal⁺ neurons throughout intercourse to know how their firing patterns relate to conduct and work together with different organs just like the mind and prostate.
And whereas the rat has lengthy reigned because the go-to mannequin for ejaculation, this research might mark a altering of the guard. “We’re not here to dethrone the rat,” says Lenschow, “but we do think the mouse has much more to contribute to our understanding of reproduction than it’s been given credit for.”
“We’re just beginning to understand how richly the spinal cord contributes as an active player to sexual behavior,” provides Mendes. “It’s not just a conduit—it’s a collaborator.”
Extra info:
A galanin-positive inhabitants of lumbar spinal twine neurons modulates sexual arousal and copulatory conduct in male mice, Nature Communications (2025). DOI: 10.1038/s41467-025-63877-2
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Champalimaud Centre for the Unknown
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Greater than a reflex: How the backbone shapes intercourse (2025, September 23)
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