Complementary Contributions of Striatal Projection Pathways to Action Initiation and Execution.

The performance of an action relies on the initiation and execution of appropriate movement sequences. Two basal ganglia pathways have been classically hypothesized to regulate this process via opposing roles in movement facilitation and suppression. By using a series of state-dependent optogenetic manipulations, we dissected the contributions of each pathway and found that both the direct striatonigral pathway and the indirect striatopallidal pathway are necessary for smooth initiation and the execution of learned action sequences. Optogenetic inhibition or stimulation of each pathway before sequence initiation increased the latency for initiation: manipulations of the striatonigral pathway activity slowed action initiation, and those of the striatopallidal pathway aborted action initiation. The inhibition of each pathway after initiation also impaired ongoing execution. Furthermore, the subtle activation of striatonigral neurons sustained the performance of learned sequences, while striatopallidal manipulations aborted ongoing performance. These results suggest a supportive versus permissive model, where patterns of coordinated activity, rather than the relative amount of activity in these pathways, regulate movement initiation and execution.

Contralateral Afferent Input to Lumbar Lamina I Neurons as a Neural Substrate for Mirror-Image Pain.

Mirror-image pain arises from pathologic alterations in the nociceptive processing network that controls functional lateralization of the primary afferent input. Although a number of clinical syndromes related to dysfunction of the lumbar afferent system are associated with the mirror-image pain, its morphophysiological substrate and mechanism of induction remain poorly understood. Therefore, we used ex vivo spinal cord preparation of young rats of both sexes to study organization and processing of the contralateral afferent input to the neurons in the major spinal nociceptive projection area Lamina I. We show that decussating primary afferent branches reach contralateral Lamina I, where 27% of neurons, including projection neurons, receive monosynaptic and/or polysynaptic excitatory drive from the contralateral Aδ-fibers and C-fibers. All these neurons also received ipsilateral input, implying their involvement in the bilateral information processing. Our data further show that the contralateral Aδ-fiber and C-fiber input is under diverse forms of inhibitory control. Attenuation of the afferent-driven presynaptic inhibition and/or disinhibition of the dorsal horn network increased the contralateral excitatory drive to Lamina I neurons and its ability to evoke action potentials. Furthermore, the contralateral Aßδ-fibers presynaptically control ipsilateral C-fiber input to Lamina I neurons. Thus, these results show that some lumbar Lamina I neurons are wired to the contralateral afferent system whose input, under normal conditions, is subject to inhibitory control. A pathologic disinhibition of the decussating pathways can open a gate controlling contralateral information flow to the nociceptive projection neurons and, thus, contribute to induction of hypersensitivity and mirror-image pain.SIGNIFICANCE STATEMENT We show that contralateral Aδ-afferents and C-afferents supply lumbar Lamina I neurons. The contralateral input is under diverse forms of inhibitory control and itself controls the ipsilateral input. Disinhibition of decussating pathways increases nociceptive drive to Lamina I neurons and may cause induction of contralateral hypersensitivity and mirror-image pain.

A Novel Route to Optimize Placement Equipment Kinematics by Coupling Capacitive Accelerometers.

Machine end-effector kinematic analysis is critical to optimizing transporting components where inertial forces are the main loads. While displacements may be measured with relatively high accuracy in transportation equipment motors, the inertial forces in the transported components are seldom optimized. This is especially relevant in electronic component placement systems, where the components have a wide range of configurations (i.e., geometry and mass) and the deployment dimensional/geometric tolerances are remarkably good. The optimization of these systems requires the monitoring of the real position of the accelerometers relative to the measurement point of interest with sufficient accuracy that allows the assembly position to be predicted instantaneously. This study shows a novel method to calibrate this equipment using triaxial accelerometers on a surface mount machine to measure the end-effector accelerations and velocities in its planar motion. The dynamic equations of the system and the method for integration are presented to address the uncertainty on the exact position of the accelerometer sensors relative to the measuring point of interest exist and allow the position correction to optimize response and accuracy.

Differential Encoding of Predator Fear in the Ventromedial Hypothalamus and Periaqueductal Grey.

The ventromedial hypothalamus is a central node of the mammalian predator defense network. Stimulation of this structure in rodents and primates elicits abrupt defensive responses, including flight, freezing, sympathetic activation, and panic, while inhibition reduces defensive responses to predators. The major efferent target of the ventromedial hypothalamus is the dorsal periaqueductal gray (dPAG), and stimulation of this structure also elicits flight, freezing, and sympathetic activation. However, reversible inhibition experiments suggest that the ventromedial hypothalamus and periaqueductal gray play distinct roles in the control of defensive behavior, with the former proposed to encode an internal state necessary for the motivation of defensive responses, while the latter serves as a motor pattern initiator. Here, we used electrophysiological recordings of single units in behaving male mice exposed to a rat to investigate the encoding of predator fear in the dorsomedial division of the ventromedial hypothalamus (VMHdm) and the dPAG. Distinct correlates of threat intensity and motor responses were found in both structures, suggesting a distributed encoding of sensory and motor features in the medial hypothalamic-brainstem instinctive network.SIGNIFICANCE STATEMENT Although behavioral responses to predatory threat are essential for survival, the underlying neuronal circuits remain undefined. Using single unit in vivo electrophysiological recordings in mice, we have identified neuronal populations in the medial hypothalamus and brainstem that encode defensive responses to a rat predator. We found that both structures encode both sensory as well as motor aspects of the behavior although with different kinetics. Our findings provide a framework for understanding how innate sensory cues are processed to elicit adaptive behavioral responses to threat and will help to identify targets for the pharmacological modulation of related pathologic behaviors.

O-Ethyl S-{(S)-1-oxo-1-[(R)-2-oxo-4-phenyl-oxazolidin-3-yl]propan-2-yl} carbonodi-thio-ate.

In the title compound, C15H17NO4S2, synthesized by addition of O-ethylxanthic acid potassium salt to a diastereomeric mixture of (4R)-3-(2-chloro-propano-yl)-4-phenyl-oxazolidin-2-one, the oxazolidinone ring has a twist conformation on the C-C bond. The phenyl ring is inclined to the mean plane of the oxazolidinone ring by 76.4 (3)°. In the chain the methine H atom is involved in a C-H⋯S and a C-H⋯O intra-molecular inter-action. In the crystal, mol-ecules are linked by C-H⋯π inter-actions, forming chains along [001]. The S configuration at the C atom to which the xanthate group is attached was determined by comparison to the known R configuration of the C atom to which the phenyl group is attached.

Functional diversity along the anteroposterior axis of the ventromedial hypothalamus.

Innate behaviors ensure animal survival and reproductive success. Defending their territory, escaping from predators or mating with a sexual partner, are fundamental behaviors determining the ecological fitness of individuals. Remarkably, all these behaviors share a common neural substrate, as they are under the control of the ventromedial hypothalamus (VMH). Decades of research have contributed to understanding the exquisite diversity of functional ensembles underlying the wide array of functions that the VMH carries out. These functional ensembles are usually distributed throughout the dorsoventral and mediolateral axes of this nucleus. However, increasing evidence is bringing to attention the functional diversity of the VMH across its anteroposterior axis. In this review, we will overview our current understanding of how different ensembles within the VMH control a wide array of animal behaviors, emphasizing the newly discovered roles for its anterior subdivision in the context of conspecific self-defense.

2-(4-Hy-droxy-phen-yl)-1H-benzimidazol-3-ium chloride monohydrate.

The title mol-ecular salt, C13H11N2O(+)·Cl(-)·H2O, crystallizes as a monohydrate. In the cation, the phenol and benzimidazole rings are almost coplanar, making a dihedral angle of 3.18 (4)°. The chloride anion and benzimidazole cation are linked by two N(+)-H⋯Cl(-) hydrogen bonds, forming chains propagating along [010]. These chains are linked through O-H⋯Cl hydrogen bonds involving the water mol-ecule and the chloride anion, which form a diamond core, giving rise to the formation of two-dimensional networks lying parallel to (10-2). Two π-π inter-actions involving the imidazolium ring with the benzene and phenol rings [centroid-centroid distances = 3.859 (3) and 3.602 (3) Å, respectively], contribute to this second dimension. A strong O-H⋯O hydrogen bond involving the water mol-ecule and the phenol substituent on the benzimidazole unit links the networks, forming a three-dimensional structure.

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.

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.

Social behavior: Closing the gap for close encounters.

Social touch can launch a cascade of emotions with enormous impact on the development and maintenance of emotional, cognitive and social functioning. A recent study identifies a novel pathway that facilitates physical contact via its direct impact on brain circuits controlling social behavior.

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.

The underestimated sex: A review on female animal models of depression.

Major depression (MD) is the most common psychiatric disorder, predicted to affect around 264 million people worldwide. Although the etiology of depression remains elusive, the interplay between genetics and environmental factors, such as early life events, stress, exposure to drugs and health problems appears to underlie its development. Whereas depression is twice more prevalent in women than in men, most preclinical studies are performed in male rodents. In fact, females' physiology and reproductive experience are associated with changes to brain, behavior and endocrine profiles that may influence both stress, an important precipitating factor for depression, and response to treatment. These specificities emphasize the need to choose the most suitable models and readouts in order to better understand the pathophysiological mechanisms of depression in females. With this review, we aim to provide an overview of female animal models of depression highlighting the major differences between models, regarding behavioral, physiological, and molecular readouts, but also the major gaps in research, attending to the role of etiological factors, protocol variability and sex.

Neural and behavioral plasticity across the female reproductive cycle.

Sex is fundamental for the evolution and survival of most species. However, sex can also pose danger, because it increases the risk of predation and disease transmission, among others. Thus, in many species, cyclic fluctuations in the concentration of sex hormones coordinate sexual receptivity and attractiveness with female reproductive capacity, promoting copulation when fertilization is possible and preventing it otherwise. In recent decades, numerous studies have reported a wide variety of sex hormone-dependent plastic rearrangements across the entire brain, including areas relevant for female sexual behavior. By contrast, how sex hormone-induced plasticity alters the computations performed by such circuits, such that collectively they produce the appropriate periodic switches in female behavior, is mostly unknown. In this review, we highlight the myriad sex hormone-induced neuronal changes known so far, the full repertoire of behavioral changes across the reproductive cycle, and the few examples where the relationship between sex hormone-dependent plasticity, neural activity, and behavior has been established. We also discuss current challenges to causally link the actions of sex hormones to the modification of specific cellular pathways and behavior, focusing on rodents as a model system while drawing a comparison between rodents and humans wherever possible.

Nematicidal activity of furanoeremophilenes against Meloidogyne incognita and Nacobbus aberrans.

BACKGROUND: While searching for novel small molecules for new organic pesticide agents against plant-parasitic nematodes, we found that the hexane extract from the roots of Senecio sinuatos and its main secondary metabolite, 3ß-angeloyloxy-6ß-hydroxyfuranoeremophil-1(10)-ene (1), possess nematicidal activity against the second stage juvenile (J2) of Meloidogyne incognita and Nacobbus aberrans. Both species reduce yield of various vegetable crops. These results encouraged us to synthesize esters 3-9 formed by diol 2, obtained by alkaline hydrolysis of 1 and acetic anhydride, benzoic acid, 2-nitrobenzoic acid, 2-bromobenzoic acid, 4-nitrobenzoic acid, 4-bromobenzoic acid, and 4-methoxybenzoic acid, respectively. The nematicidal activity of these esters was evaluated and compared with that of the free benzoic acids. RESULTS: Natural product 1 and derivatives 2-9 were obtained and characterized by their physical and spectroscopic properties, including one-dimensional (1D) and two-dimensional (2D) nuclear magnetic resonance (NMR) experiments; X-ray diffraction analysis established their absolute configuration. The nematicidal activity of compounds 1-9 was assessed in vitro against M. incognita and N. aberrans J2 and was compared to activity shown by benzoic acid, 2-nitrobenzoic acid, 2-bromobenzoic acid, 4-nitrobenzoic acid, 4-bromobenzoic acid, and 4-methoxybenzoic acid. The esters suppressed nematodes more than free benzoic acid. Nacobbus aberrans J2 were suppressed, with compounds 5, 6, and 8 being the most active. CONCLUSION: Esters formed by 3ß,6ß-dihydroxyfuranoeremophil-1(10)-ene and ortho- or para-substituted benzoic acids containing electron acceptor groups had nematicidal activity against N. aberrans. These compound can potentially serve as a model for the development of new organic nematicidal agents. © 2022 Society of Chemical Industry.

No evidence for prolactin's involvement in the post-ejaculatory refractory period.

In many species, ejaculation is followed by a state of decreased sexual activity, the post-ejaculatory refractory period. Several lines of evidence have suggested prolactin, a pituitary hormone released around the time of ejaculation in humans and other animals, to be a decisive player in the establishment of the refractory period. However, data supporting this hypothesis is controversial. We took advantage of two different strains of house mouse, a wild derived and a classical laboratory strain that differ substantially in their sexual performance, to investigate prolactin's involvement in sexual activity and the refractory period. First, we show that there is prolactin release during sexual behavior in male mice. Second, using a pharmacological approach, we show that acute manipulations of prolactin levels, either mimicking the natural release during sexual behavior or inhibiting its occurrence, do not affect sexual activity or shorten the refractory period, respectively. Therefore, we show compelling evidence refuting the idea that prolactin released during copulation is involved in the establishment of the refractory period, a long-standing hypothesis in the field of behavioral endocrinology.

The Structural and Electrophysiological Properties of Progesterone Receptor-Expressing Neurons Vary along the Anterior-Posterior Axis of the Ventromedial Hypothalamus and Undergo Local Changes across the Reproductive Cycle.

Sex hormone levels continuously fluctuate across the reproductive cycle, changing the activity of neuronal circuits to coordinate female behavior and reproductive capacity. The ventrolateral division of the ventromedial hypothalamus (VMHvl) contains neurons expressing receptors for sex hormones and its function is intimately linked to female sexual receptivity. However, recent findings suggest that the VMHvl is functionally heterogeneous. Here, we used whole recordings and intracellular labeling to characterize the electrophysiological and morphologic properties of individual VMHvl neurons in naturally cycling females and report the existence of multiple electrophysiological phenotypes within the VMHvl. We found that the properties of progesterone receptor expressing (PR+) neurons, but not PR- neurons, depended systematically on the neuron's location along the anterior-posterior (AP) axis of the VMHvl and the phase within the reproductive cycle. Prominent among this, the resting membrane potential of anterior PR+ neurons decreased during the receptive phase, while the excitability of medial PR+ neurons increased during the non-receptive phase. During the receptive phase of the cycle, posterior PR+ neurons simultaneously showed an increase in dendritic complexity and a decrease in spine density. These findings reveal an extensive diversity of local rules driving structural and physiological changes in response to fluctuating levels of sex hormones, supporting the anatomic and functional subdivision of the VMHvl and its possible role in the orchestration of different aspects of female socio-sexual behavior.

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.

Sexual imprinting overrides order effects during sampling of prospective mates.

Through crossfostering experiments between two subspecies of mice, Moreira et al. show that females normally undergo sexual imprinting early in life. When fostered by individuals from another subspecies, they tend to prefer males from the sub-species they first encounter, suggesting sexual imprinting normally over-rides this inclination.

Lack of Safe Drinking Water for Lake Chapala Basin Communities in Mexico Inhibits Progress toward Sustainable Development Goals 3 and 6.

BACKGROUND: Access to safe, affordable and accessible drinking water is a human right and foundational to the third and sixth World Health Organization's Sustainable Development Goals (SDGs). Unsafe drinking water is a risk factor for chronic and enteric diseases. Both chronic kidney disease (CKD) and diarrheal disease are highly prevalent in the Lake Chapala basin, Jalisco, Mexico, suggesting disparities in factors leading to successful achievement of these two SDGs. METHODS: This study aimed to assess progress towards SDG three and six in the Lake Chapala basin. Qualitative, quantitative, and geospatial data were collected between May and August of 2019 from three towns within the municipalities of Poncitlán and Chapala. RESULTS: Ninety-nine households participated in this study. Water sampling analyses determined 81.18% of samples from water jugs (garrafones) and 70.05% of samples from tap water were contaminated with total coliform bacteria, often including E. coli. Additionally, 32% of garrafón samples and 61.9% of tap water samples had detectable levels of arsenic. Approximately 97.94% of respondents stated that they believe clean water is a human right, but 78.57% feel the Mexican government does not do enough to make this a reality. CONCLUSIONS: This mixed methods approach highlights water quality as a serious issue in communities around Lake Chapala, and demonstrates inadequate drinking water as a key hazard, potentially perpetuating the high disease burden of both CKD and enteric disease in the region.