Study reveals how a key spinal circuit shapes the choreography of sex

For decades, it was thought that while the brain orchestrated male sexual behaviour – arousal, courtship, and copulation – the spinal cord merely executed the final act: ejaculation. But a study from the Champalimaud Foundation (CF) challenges that tidy division. It reveals that a key spinal circuit is not only involved in ejaculation but also in arousal and shaping the choreography of sex, adding a surprising new dimension to our understanding of sexual behaviour in mammals.

The spinal cord isn’t just a passive relay station executing brain commands. 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”.

Susana Lima, Principal Investigator of CF’s Neuroethology Lab and senior author of the study

The neurons that drive the drivers

“We were initially interested in female sexual behaviour”, recalls 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 team began with a deceptively simple question: which neurons control the muscle responsible for ejaculation?

“The muscle in question is the bulbospongiosus, or BSM”, explains Constanze Lenschow, co-lead author and now Group Leader at the INCIA Institute at the University 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 trace the origins of this signal, the team used anatomical tracing techniques to map the pathway from the BSM back to its motor neurons, the cells that directly command it to contract. They then looked one step further: which neurons control those motor neurons? Initial attempts to map connections using a rabies virus tracer hit a wall. “It was frustrating”, says co-first author Ana Rita Mendes, who joined the project during her MSc. “So we switched tactics”.

Earlier work in rats had identified a group of spinal neurons expressing a molecule called galanin (Gal) as key to ejaculation. Building on this, the team used genetically modified mice in which Gal-expressing (Gal⁺) neurons fluoresced red. Under the microscope, they saw that the axons – long projections that transmit signals – of these Gal⁺ neurons overlapped with the BSM motor neurons, suggesting a direct link.

To test this, Lenschow performed patch-clamp electrophysiology in spinal cord 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 first time a functional, 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 team showed that Gal⁺ neurons receive sensory input from the penis. In spinalised mice – where the spinal cord is severed from the brain – a light puff of air to the penis activated both Gal⁺ neurons and BSM motor neurons, confirming that the circuit is sensitive to genital stimulation.

Turning on the sex circuit

To test whether these Gal⁺ neurons could actually drive ejaculation, the team used either electrical stimulation or a more precise method called optogenetics, which enabled them to selectively activate Gal⁺ neurons in genetically modified mice using light.

In rats, stimulating these neurons reliably triggers ejaculation. But in mice, things didn’t go as expected. “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, robust BSM activity only occurred in spinalised mice, where brain input was removed. This suggests that descending signals from the brain actively suppress the spinal circuit – until the right moment. “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 together, the results suggest that Gal⁺ neurons receive sensory input, weigh internal and external signals, initiate the motor pattern that ends in ejaculation – and then step aside. But there was one more 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 other words, the spinal cord seemed to “know” whether or not the mouse had recently ejaculated. “That’s a level of context sensitivity we don’t typically associate with spinal circuits”, adds Mendes.

Of mice and men: A better fit than rats?

The researchers then asked: what happens if we use a targeted toxin to selectively eliminate Gal⁺ neurons in live 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 healthy mice integrate touch or mechanical feedback, as well as influence arousal and the pacing of sexual behaviour. “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 more like a reflex – genital stimulation is often enough to trigger it, sometimes during the first mount. Mice, by contrast, engage in repeated mounts and thrusts before ejaculation, resembling the gradual build-up seen in humans.

“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 challenge the traditional top-down view of sexual control and lead to a rethinking of how ejaculation is controlled. Instead of the brain simply commanding the spinal cord to act, the two appear to be in continuous dialogue – with the Gal⁺ spinal neurons receiving sensory input, modulating motor output, and integrating signals related to arousal and internal state. This spinal integration may even contribute to the refractory period, the temporary lull in sexual responsiveness after ejaculation, suggesting that the spinal cord itself helps control when the system is ready to go again, contrary to current thinking.

“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 fact, Lima speculates that the “point of no return” – the moment after which ejaculation is inevitable – may not come from the brain at all, but from the prostate, acting like an internal status update: “I’m ready. Time to go”.

Beyond basic biology, these findings open new avenues for understanding sexual dysfunction and erectile disorders. The team’s next step is to record directly from Gal⁺ neurons during sex to understand how their firing patterns relate to behaviour and interact with other organs like the brain and prostate.

And while the rat has long reigned as the go-to model for ejaculation, this study may mark a changing 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 behaviour”, adds Mendes. “It’s not just a conduit – it’s a collaborator”.