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Graphical abstractSummaryDuring sex, male arousal increases up to the ejaculatory threshold, allowing genital sensory input to trigger ejaculation. While copulation and arousal increase are thought to be centrally regulated, ejaculation is a reflex controlled by a spinal circuit, whose activity is strongly inhibited by descending input from the brain, bearing no role on the regulation of sexual behavior up until the arousal threshold. However, this hypothesis remains untested. To tackle this problem, we combined genetic approaches with electrophysiological and behavioral analysis to functionally map the spinal circuit controlling the main muscle involved in sperm expulsion, the bulbospongiosus muscle (BSM). We found that BSM motor neurons (BSM-MNs) receive direct synaptic input from a group of galanin-expressing (Gal+) interneurons located in the upper lumbar spinal cord. Furthermore, the Gal+ population is progressively activated during sexual behavior and receives genital sensory input. Electrical and optogenetic activation of the Gal+ neurons evoked activity in BSM-MNs and BSM after spinalization. Interestingly, these effects were dependent on the behavioral state of the male and drastically decreased with repeated stimulation. Moreover, genetic ablation of the Gal+ neurons severely impacted the latency to ejaculate and the structure of the copulatory sequence. Taken together, our results imply an unexpected involvement of the spinal cord in the control of copulatory behavior, sexual arousal and in the post-ejaculatory refractory period, in addition to its well established role in ejaculation.

Sex is pervasive in nature. Yet, despite its importance for species maintenance and evolution, sex is unnecessary for the survival of the individual, it can have a negative impact on fitness and is performed by most species (except our own) without awareness of its consequences: fertilization. A myriad of mechanisms has evolved to promote its fruitful execution, such that sex it promoted when fertilization is most likely to occur and inhibited otherwise. In this review we present recent advances in our knowledge of the neuronal circuits underlying sexual behaviour. We discuss flies, rats and mice to underline the breadth of existing neuronal strategies used to accomplish the appropriate execution of this behaviour, while still highlighting shared principles across such distinct taxa.

How does social and sexual information processing map onto cortical circuits? Addressing this question has been difficult, because of a lack of circuit-oriented social neuroscience and an absence of measurements from interacting brains. Recent work showed social information is already differentially processed in the primary sensory cortices. Converging evidence suggests that prefrontal areas contribute to social interaction processing and determining social hierarchies. In social interactions, we identify gender in split seconds, but after centuries of anatomy we are still unable to distinguish male and female cortices. Novel data reinforce the idea of a bisexual layout of cortical anatomy. Physiological analysis, however, provided evidence for sex differences in cortical processing. Unlike other cortical circuits, sexual processing circuits undergo major rewiring and expansion during puberty and show lasting damage from childhood abuse.

Rat somatosensory genital cortex contains a large sexually monomorphic representation of the penis in males and the clitoris in females. Genital cortex microstimulation-evoked movements of legs, trunk and genitals, which showed sex-specific differences related to mating behaviors and included thrusting in males and lordosis-like movements in females. Erections/tumescence of penis or clitoris could not be evoked, however. Anterograde tracer injections into penis/clitoris cortex revealed eleven corticocortical and 10 subcortical projection targets, which were qualitatively similar in both sexes. Corticocortical genital-cortex-projections innervated about 3% of the cortical surface and most were analog to other somatosensory projections targeting motor cortex, secondary somatosensory cortex, parietal cortex and perirhinal cortex. Corticocortical projections that differed from other parts of somatosensory cortex targeted male scrotum cortex, female vulva cortex, the somatosensory–ear–auditory-cortex-region and the caudal parietal area. Aligning cytoarchitectonic borders with motor topography, sensory genital responses and corticocortical projections identified a candidate region for genital motor cortex. Most subcortical genital-cortex-projections were analog to other thalamic, tectal or pontine projections of somatosensory cortex. Genital-cortex-specific subcortical projections targeted amygdala and nucleus submedius and accumbens. Microstimulation-effects and projections support a sexual function of genital cortex and suggest that genital cortex is a major hub of sexual sensorimotor processing in rodents.

Anatomical, stimulation and lesion data implicate vibrissa motor cortex in whisker motor control. Work on motor cortex has focused on movement generation, but correlations between vibrissa motor cortex activity and whisking are weak. The exact role of vibrissa motor cortex remains unknown. We recorded vibrissa motor cortex neurons during various forms of vibrissal touch, which were invariably associated with whisker protraction and movement. Free whisking, object palpation and social touch all resulted in decreased cortical activity. To understand this activity decrease, we performed juxtacellular recordings, nanostimulation and in vivo whole-cell recordings. Social touch resulted in decreased spiking activity, decreased cell excitability and membrane hyperpolarization. Activation of vibrissa motor cortex by intracortical microstimulation elicited whisker retraction, as if to abort vibrissal touch. Various vibrissa motor cortex inactivation protocols resulted in contralateral protraction and increased whisker movements. These data collectively point to movement suppression as a prime function of vibrissa motor cortex activity.

SummaryFemale mammals experience cyclical changes in sexual receptivity known as the estrus-cycle. Little is known about how estrus affects the cortex although alterations in sensation, cognition and the cyclic occurrence of epilepsy suggest brain-wide processing changes. We performedin vivojuxtacellular and whole-cell recordings in somatosensory cortex of female rats and found that the estrus-cycle potently altered cortical inhibition. Fast-spiking interneurons strongly varied their activity with the estrus-cycle and estradiol in ovariectomized females, while regular-spiking excitatory neurons did not change.In vivowhole-cell recordings revealed a varying excitation-to-inhibition-ratio with estrus.In situhybridization for estrogen receptor β (Esr2) showed co-localization with parvalbumin-positive interneurons in deep cortical layers, mirroring the laminar distribution of our physiological findings.In vivoandin vitroexperiments confirmed that estrogen acts locally to increase fast-spiking interneuron excitability through an estrogen receptor β mechanism. We conclude that sex hormones powerfully modulate cortical inhibition in the female brain.

Female mammals experience cyclical changes in sexual receptivity known as the estrus-cycle. Little is known about how estrus affects the cortex although alterations in sensation, cognition and the cyclic occurrence of epilepsy suggest brain-wide processing changes. We performed in vivo juxtacellular and whole-cell recordings in somatosensory cortex of female rats and found that the estrus-cycle potently altered cortical inhibition. Fast-spiking interneurons strongly varied their activity with the estrus-cycle and estradiol in ovariectomized females, while regular-spiking excitatory neurons did not change. In vivo whole-cell recordings revealed a varying excitation-to-inhibition-ratio with estrus. In situ hybridization for estrogen receptor β (Esr2) showed co-localization with parvalbumin-positive interneurons in deep cortical layers, mirroring the laminar distribution of our physiological findings. In vivo and in vitro experiments confirmed that estrogen acts locally to increase fastspiking interneuron excitability through an estrogen receptor β mechanism. We conclude that sex hormones powerfully modulate cortical inhibition in the female brain.

SummaryThe impact of social stimuli on the membrane potential dynamics of barrel cortex neurons is unknown. We obtained in vivo whole-cell recordings in the barrel cortex of head-restrained rats while they interacted with conspecifics. Social touch was associated with a depolarization and large membrane potential fluctuations locked to the rat’s whisking. Both depolarization and membrane potential fluctuations were already observed prior to contact and did not occur during free whisking. This anticipatory pre-contact depolarization was not seen in passive social touch in anesthetized animals. The membrane potential fluctuations locked to the rat’s whisking observed in interactions with awake conspecifics were larger than those seen for whisking onto nonconspecific stimuli (stuffed rats, objects, and the experimenter’s hand). Responses did not correlate with whisker movement parameters. We conclude that responses to social touch differ from conventional tactile responses in (1) amplitude, (2) locking to whisking, and (3) pre-contact membrane potential changes.

The mammalian somatosensory cortex shows marked species‐specific differences. How evolution in general and sexual selection in particular shape the somatosensory cortical body representation has not been delineated, however. Here we address this issue by a comparative analysis of genital cortex. Genitals are unique body parts in that they show sexual dimorphism, major changes in puberty and typically more pronounced species differences than other body parts (Hosken & Stockley, 2004). To study the evolution of genital cortex we flattened cortical hemispheres and assembled 104 complete body maps, revealed by cytochrome‐oxidase activity in layer 4 of 8 rodent and 1 lagomorph species. In two species, we also performed antibody stainings against vesicular glutamate transporter‐2, which suggested that cytochrome‐oxidase maps closely mirror thalamic innervation. We consistently observed a protrusion between hindlimb and forelimb representation, which in rats (Lenschow et al., 2016) corresponds to the penis representation in males and the clitoris representation in females. Consistent with the idea that this protrusion corresponds to genital cortex, we observed a size increase of this protrusion during puberty. Species differed in external genital sexual dimorphism, but we observed a sexual monomorphism of the putative genital protrusion in all species, similar to previous observations in rats. The relative size of the putative genital protrusion varied more than 3‐fold between species ranging from 0.5% of somatosensory cortex area in chipmunks to 1.7% in rats. This relative size of the genital protrusion co‐varied with relative testicle size, an indicator of sperm competition and sexual selection.

Activity-dependent synaptic plasticity (ADSP) is paramount to synaptic processing and maturation. However, identifying the ADSP capabilities of the numerous synapses converging onto spinal motoneurons (MNs) remain elusive. Using spinal cord slices from mice at two developmental stages, 1–4 and 8–12 postnatal days (P1–P4; P8–P12), we found that high-frequency stimulation of presumed reticulospinal neuron axons in the ventrolateral funiculus (VLF) induced either an NMDA receptor-dependent-long-term depression (LTD), a short-term depression (STD) or no synaptic modulation in limb MNs. Our study shows that P1–P4 cervical MNs expressed the same plasticity profiles as P8–P12 lumbar MNs rather than P1–P4 lumbar MNs indicating that ADSP expression at VLF-MN synapses is linked to the rostrocaudal development of spinal motor circuitry. Interestingly, we observed that the ADSP expressed at VLF-MN was related to the functional flexor or extensor MN subtype. Moreover, heterosynaptic plasticity was triggered in MNs by VLF axon tetanisation at neighbouring synapses not directly involved in the plasticity induction. ADSP at VLF-MN synapses specify differential integrative synaptic processing by flexor and extensor MNs and could contribute to the maturation of spinal motor circuits and developmental acquisition of weight-bearing locomotion.

Mammalian external genitals show sexual dimorphism [1, 2] and can change size and shape upon sexual arousal. Genitals feature prominently in the oldest pieces of figural art [3] and phallic depictions of penises informed psychoanalytic thought about sexuality [4, 5]. Despite this longstanding interest, the neural representations of genitals are still poorly understood [6]. In somatosensory cortex specifically, many studies did not detect any cortical representation of genitals [7-9]. Studies in humans debate whether genitals are represented displaced below the foot of the cortical body map [10-12] or whether they are represented somatotopically [13-15]. We wondered what a high-resolution mapping of genital representations might tell us about the sexual differentiation of the mammalian brain. We identified genital responses in rat somatosensory cortex in a region previously assigned as arm/leg cortex. Genital responses were more common in males than in females. Despite such response dimorphism, we observed a stunning anatomical monomorphism of cortical penis and clitoris input maps revealed by cytochrome-oxidase-staining of cortical layer 4. Genital representations were somatotopic and bilaterally symmetric, and their relative size increased markedly during puberty. Size, shape, and erect posture give the cortical penis representation a phallic appearance pointing to a role in sexually aroused states. Cortical genital neurons showed unusual multi-body-part responses and sexually dimorphic receptive fields. Specifically, genital neurons were co-activated by distant body regions, which are touched during mounting in the respective sex. Genital maps indicate a deep homology of penis and clitoris representations in line with a fundamentally bi-sexual layout [16] of the vertebrate brain.

Many insects use the pattern of polarized light in the sky for spatial orientation and navigation. We have investigated the polarization vision system in the desert locust. To create a common platform for anatomical studies on polarization vision pathways, Kurylas et al. (2008) have generated a three-dimensional (3D) standard brain from confocal microscopy image stacks of 10 male brains, using two different standardization methods, the Iterative Shape Averaging (ISA) procedure and the Virtual Insect Brain (VIB) protocol. Comparison of both standardization methods showed that the VIB standard is ideal for comparative volume analysis of neuropils, whereas the ISA standard is the method of choice to analyze the morphology and connectivity of neurons. The central complex is a key processing stage for polarization information in the locust brain. To investigate neuronal connections between diverse central-complex neurons, we generated a higher-resolution standard atlas of the central complex and surrounding areas, using the ISA method based on brain sections from 20 individual central complexes. To explore the usefulness of this atlas, two central-complex neurons, a polarization-sensitive columnar neuron (type CPU1a) and a tangential neuron that is activated during flight, the giant-fan shaped (GFS) neuron, were reconstructed three-dimensionally from brain sections. To examine whether the GFS neuron is a candidate to contribute to synaptic input to the CPU1a neuron, we registered both neurons into the standardized central complex. Visualization of both neurons revealed a potential connection of the CPU1a and GFS neurons in layer II of the upper division of the central body.