Myomatrix arrays for high-definition muscle recording.

Neurons coordinate their activity to produce an astonishing variety of motor behaviors. Our present understanding of motor control has grown rapidly thanks to new methods for recording and analyzing populations of many individual neurons over time. In contrast, current methods for recording the nervous system's actual motor output - the activation of muscle fibers by motor neurons - typically cannot detect the individual electrical events produced by muscle fibers during natural behaviors and scale poorly across species and muscle groups. Here we present a novel class of electrode devices ('Myomatrix arrays') that record muscle activity at unprecedented resolution across muscles and behaviors. High-density, flexible electrode arrays allow for stable recordings from the muscle fibers activated by a single motor neuron, called a 'motor unit,' during natural behaviors in many species, including mice, rats, primates, songbirds, frogs, and insects. This technology therefore allows the nervous system's motor output to be monitored in unprecedented detail during complex behaviors across species and muscle morphologies. We anticipate that this technology will allow rapid advances in understanding the neural control of behavior and identifying pathologies of the motor system.

Socio-sexual touch: On the hunt for a pleasure signal in the mouse brain.

Skin-to-skin contact is widespread during social interactions and essential for establishing intimate relationships. To understand the skin-to-brain circuits underlying pleasurable touch, a new study has used mouse genetic tools to specifically target and study sensory neurons that transmit social touch and their role during sexual behavior in mice.

Myomatrix arrays for high-definition muscle recording.

Neurons coordinate their activity to produce an astonishing variety of motor behaviors. Our present understanding of motor control has grown rapidly thanks to new methods for recording and analyzing populations of many individual neurons over time. In contrast, current methods for recording the nervous system's actual motor output - the activation of muscle fibers by motor neurons - typically cannot detect the individual electrical events produced by muscle fibers during natural behaviors and scale poorly across species and muscle groups. Here we present a novel class of electrode devices ("Myomatrix arrays") that record muscle activity at unprecedented resolution across muscles and behaviors. High-density, flexible electrode arrays allow for stable recordings from the muscle fibers activated by a single motor neuron, called a "motor unit", during natural behaviors in many species, including mice, rats, primates, songbirds, frogs, and insects. This technology therefore allows the nervous system's motor output to be monitored in unprecedented detail during complex behaviors across species and muscle morphologies. We anticipate that this technology will allow rapid advances in understanding the neural control of behavior and in identifying pathologies of the motor system.

Hearing, touching, and multisensory integration during mate choice.

Mate choice is a potent generator of diversity and a fundamental pillar for sexual selection and evolution. Mate choice is a multistage affair, where complex sensory information and elaborate actions are used to identify, scrutinize, and evaluate potential mating partners. While widely accepted that communication during mate assessment relies on multimodal cues, most studies investigating the mechanisms controlling this fundamental behavior have restricted their focus to the dominant sensory modality used by the species under examination, such as vision in humans and smell in rodents. However, despite their undeniable importance for the initial recognition, attraction, and approach towards a potential mate, other modalities gain relevance as the interaction progresses, amongst which are touch and audition. In this review, we will: (1) focus on recent findings of how touch and audition can contribute to the evaluation and choice of mating partners, and (2) outline our current knowledge regarding the neuronal circuits processing touch and audition (amongst others) in the context of mate choice and ask (3) how these neural circuits are connected to areas that have been studied in the light of multisensory integration.

In the mood for sex: neural circuits for reproduction.

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.

Estrus-Cycle Regulation of Cortical Inhibition.

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 cyclical 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 were strongly activated with social facial touch and varied their ongoing activity with the estrus cycle and estradiol in ovariectomized females, while regular-spiking excitatory neurons did not change. In situ hybridization for estrogen receptor ß (Esr2) showed co-localization with parvalbumin-positive (PV+) interneurons in deep cortical layers, mirroring the laminar distribution of our physiological findings. The fraction of neurons positive for estrogen receptor ß (Esr2) and PV co-localization (Esr2+PV+) in cortical layer V was increased in proestrus. In vivo and in vitro experiments confirmed that estrogen acts locally to increase fast-spiking interneuron excitability through an estrogen-receptor-ß-dependent mechanism.

Socio-sexual processing in cortical circuits.

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.

Physiological and Anatomical Outputs of Rat Genital Cortex.

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.

Development of rat female genital cortex and control of female puberty by sexual touch.

Rat somatosensory cortex contains a large sexually monomorphic genital representation. Genital cortex undergoes an unusual 2-fold expansion during puberty. Here, we investigate genital cortex development and female rat sexual maturation. Ovariectomies and estradiol injections suggested sex hormones cause the pubertal genital cortex expansion but not its maintenance at adult size. Genital cortex expanded by thalamic afferents invading surrounding dysgranular cortex. Genital touch was a dominant factor driving female sexual maturation. Raising female rats in contact with adult males promoted genital cortex expansion, whereas contact to adult females or nontactile (audio-visual-olfactory) male cues did not. Genital touch imposed by human experimenters powerfully advanced female genital cortex development and sexual maturation. Long-term blocking of genital cortex by tetrodotoxin in pubescent females housed with males prevented genital cortex expansion and decelerated vaginal opening. Sex hormones, sexual experience, and neural activity shape genital cortex, which contributes to the puberty promoting effects of sexual touch.

Sexually selected size differences and conserved sexual monomorphism of genital cortex.

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.

Vibrissa motor cortex activity suppresses contralateral whisking behavior.

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.

Distinct and developmentally regulated activity-dependent plasticity at descending glutamatergic synapses on flexor and extensor motoneurons.

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.

Sexually Monomorphic Maps and Dimorphic Responses in Rat Genital Cortex.

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.

Barrel cortex membrane potential dynamics in social touch.

The 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 Locust Standard Brain: A 3D Standard of the Central Complex as a Platform for Neural Network Analysis.

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 3D 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.