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Rationale Despite variants in the Dlgap1 gene having the two lowest p -value in a genome-wide association study of obsessive compulsive disorder (OCD), previous studies reported the absence of OCD-like phenotypes in Dlgap1 knockout (KO) mice. Since these studies observed behavioral phenotypes only for a short period, development of OCD-like phenotypes in these mice at older ages was still plausible. Objective To examine the presence or absence of development of OCD-like phenotypes in Dlgap1 KO mice and their responsiveness to fluvoxamine. Methods and results Newly produced Dlgap1 KO mice were observed for a year. Modified SHIRPA primary screen in 2-month-old homozygous mutant mice showed only weak signs of anxiety, stress conditions and aggression. At older ages, however, these mutant mice exhibited excessive self-grooming characterized by increased scratching which led to skin lesions. A significant sex difference was observed in this scratching behavior. The penetrance of skin lesions reached 50% at 6–7 months of age and 90% at 12 months of age. In the open-field test performed just after the appearance of these lesions, homozygous mutant mice spent significantly less time in the center, an anxiety-like behavior, than did their wild-type and heterozygous littermates, none and less than 10% of which showed skin lesions at 1 year, respectively. The skin lesions and excessive self-grooming were significantly alleviated by two-week treatment with fluvoxamine. Conclusion Usefulness of Dlgap1 KO mice as a tool for investigating the pathogenesis of OCD-like phenotypes and its translational relevance was suggested.

IntroductionIn semi-natural environments, pigs have been observed rubbing or scratching against trees and bushes, and in commercial settings, they often rub against pen structures and may allow handlers to scratch them. Whilst human-applied scratching of pigs has been studied, little is known about their self-scratching behaviour. Research on brush use in cattle suggests potential welfare benefits, while research on brushing behaviour in pigs is, to the best of our knowledge, absent. To address this gap, this study investigated whether gestating sows use a mechanical brush when housed in a social setting; how brushing varied in duration, frequency, body region, and time of day; and whether individuals differed in brush use.Materials and methodsThe study was conducted on 29 loose-housed gestating Yorkshire sows with access to deep straw bedding, a transponder-controlled feeder, and a mechanical brush (Comfort Pig, Comfy-Solutions B.V., Roelofarendsveen, the Netherlands). Observations included 192 h of continuous video recordings covering the brush area. An ethogram adapted from cattle studies and refined for pigs was applied to record brushing, sniffing, oral manipulation, and displacements. Brushing was further categorised by body region, initiation, intensity, and duration. Data were summarised descriptively, and differences between groups, times, and individuals were assessed using nonparametric methods.ResultsAll sows engaged in brushing at least once, during the study, averaging 1.5 (interquartile range, IQR = 1–2) bouts per day. The median bout duration was 12 s (IQR = 8–17), with active brushing comprising nearly half of the total time. Brushing was mainly directed to the middle body region (29.8%) and often initiated at the head (46.2%). No consistent diurnal pattern was evident. Sniffing preceded brushing in 85 of the 297 observed brushing bouts, whilst oral manipulation was only observed five times. Incomplete bouts and occasional displacements (3% of bouts) suggest that internal and social factors may influence access.ConclusionTaken together, this study provides an initial systematic description of the brushing behaviour in pigs and suggests that mechanical brushes may serve as an enriching resource for pigs in production. Further research, including comparisons across different brush types, production stages, pig-to-brush ratios, and housing systems, is needed to evaluate their potential as welfare-enhancing tools in commercial pig production.

Itch is an annoying sensation consisting of both sensory and emotional components. It is known to involve the parabrachial nucleus (PBN), but the following transmission nodes remain elusive. The present study identified that the PBN-central medial thalamic nucleus (CM)-medial prefrontal cortex (mPFC) pathway is essential for itch signal transmission at the supraspinal level in male mice. Chemogenetic inhibition of the CM-mPFC pathway attenuates scratching behavior or chronic itch-related affective responses. CM input to mPFC pyramidal neurons is enhanced in acute and chronic itch models. Specifically chronic itch stimuli also alter mPFC interneuron involvement, resulting in enhanced feedforward inhibition and a distorted excitatory/inhibitory balance in mPFC pyramidal neurons. The present work underscores CM as a transmit node of the itch signal in the thalamus, which is dynamically engaged in both the sensory and affective dimensions of itch with different stimulus salience. Itch is known to involve the parabrachial nucleus, but the following transmission nodes remain elusive. Here, the authors show in male mice that the central medial thalamic nucleus—medial prefrontal cortex (mPFC) pathway transmits itch signals and is involved in both acute scratching and chronic itch-related affective behavior, with an altered excitatory/inhibitory balance in mPFC in chronic itch models.

Although itch sensation is an important protective mechanism for animals, chronic itch remains a challenging clinical problem. Itch processing has been studied extensively at the spinal level. However, how itch information is transmitted to the brain and what central circuits underlie the itch-induced scratching behavior remain largely unknown. We found that the spinoparabrachial pathway was activated during itch processing and that optogenetic suppression of this pathway impaired itch-induced scratching behaviors. Itch-mediating spinal neurons, which express the gastrin-releasing peptide receptor, are disynaptically connected to the parabrachial nucleus via glutamatergic spinal projection neurons. Blockade of synaptic output of glutamatergic neurons in the parabrachial nucleus suppressed pruritogen-induced scratching behavior. Thus, our studies reveal a central neural circuit that is critical for itch signal processing.

Socially contagious itch is ubiquitous in human society, but whether it exists in rodents is unclear. Using a behavioral paradigm that does not entail prior training or reward, we found that mice scratched after observing a conspecific scratching. Molecular mapping showed increased neuronal activity in the suprachiasmatic nucleus (SCN) of the hypothalamus of mice that displayed contagious scratching. Ablation of gastrin-releasing peptide receptor (GRPR) or GRPR neurons in the SCN abolished contagious scratching behavior, which was recapitulated by chemogenetic inhibition of SCN GRP neurons. Activation of SCN GRP/GRPR neurons evoked scratching behavior. These data demonstrate that GRP-GRPR signaling is necessary and sufficient for transmitting contagious itch information in the SCN. The findings may have implications for our understanding of neural circuits that control socially contagious behaviors.

Green sea turtles Chelonia mydas have the ability to hear and produce sounds under water, with some of them potentially involved in social communication. To investigate the potential biological function of these sounds, we used a combination of acoustic, video and multi-sensor recordings of 23 free-ranging juvenile green turtles and we examined the co-occurrences of sounds with behaviours or external events. Our study revealed that most of the sounds were produced when the sea turtles were resting or swimming. However, four sound types were produced in more specific contexts. Long sequences of rumbles were recorded after sunset and mainly during resting. All these rumbles appear to have been produced by several individuals recorded simultaneously, suggesting that rumbles may be used for social interactions. The frequency modulated sound was highly associated with scratching behaviour. The grunt that was produced occasionally when green turtles were vigilant or approaching a conspecific. The long squeak was produced significantly by a small number of individuals in the presence of humans. The grunt and the long squeak may be the first evidence of an alarm or warning signal for intra-specific communication in green turtles. Our results mark a significant milestone in advancing the understanding of sound production in the behavioural ecology of sea turtles. Further experimental investigations (i.e., playback experiments) are now required to test the hypotheses suggested by our findings. Warning signals could be used to prevent sea turtles of a danger and may contribute to their conservation. Significance statement Underwater sound production in Chelonioidea is yet not well documented. We investigated the contexts of sound production in green sea turtles. Our results show that juvenile green sea turtles produced at least 4 identified sounds in specific contexts. This is a crucial step, as it will provide a solid basis for understanding the acoustic behaviour of green sea turtles and for improving current conservation methods. To date, the lack of knowledge on sea turtle behavioural ecology and acoustic communication hinders the implementation of mitigation measures to effectively reduce mortality and disturbance from human activities. Our findings offer the possibility of using species-specific sounds in a deterrent system to prevent them from potentially dangerous areas, including areas where seismic surveys, construction work, or areas with fishing activities (fishing nets) occurs with the aim of reducing the risk of temporary or permanent hearing damage or accidental by-catch.

Itch (pruritis) and pain represent two distinct sensory modalities; yet both have evolved to alert us to potentially harmful external stimuli. Compared with pain, our understanding of itch is still nascent. Here, we report a new clinical case of debilitating itch and altered pain perception resulting from the heterozygous de novo p.L811P gain-of-function mutation in NaV1.9, a voltage-gated sodium (NaV) channel subtype that relays sensory information from the periphery to the spine. To investigate the role of NaV1.9 in itch, we developed a mouse line in which the channel is N-terminally tagged with a fluorescent protein, thereby enabling the reliable identification and biophysical characterization of NaV1.9-expressing neurons. We also assessed NaV1.9 involvement in itch by using a newly created NaV1.9-/- and NaV1.9L799P/WT mouse model. We found that NaV1.9 is expressed in a subset of nonmyelinated, nonpeptidergic small-diameter dorsal root ganglia (DRGs). In WT DRGs, but not those of NaV1.9-/- mice, pruritogens altered action potential parameters and NaV channel gating properties. Additionally, NaV1.9-/- mice exhibited a strong reduction in acute scratching behavior in response to pruritogens, whereas NaV1.9L799P/WT mice displayed increased spontaneous scratching. Altogether, our data suggest an important contribution of NaV1.9 to itch signaling.

Chronic pruritus is a debilitating symptom with limited treatment options. Identifying molecular targets underlying chronic pruritic dermatoses is essential for the development of novel, targeted therapies. IL-31 is an important mediator of itch by integrating dermatologic, neural, and immune systems. IL-31 helps induce and maintain chronic pruritus via both indirect stimulation of inflammatory cells and through direct neural sensitization. IL-31 is overexpressed in various chronic pruritic skin conditions, and exogenous IL-31 induces itch and scratching behavior. Studies have demonstrated that IL-31R and IL-31 antagonism significantly reduces itch in patients with atopic dermatitis and prurigo nodularis, two extremely pruritic skin conditions. Emerging evidence, including recent phase II clinical trials of IL-31R antagonists, demonstrates that IL-31 plays an important role in itch signaling. Additional studies are ongoing to evaluate IL-31R and IL-31 antagonism as treatments of chronic pruritus.

Atopic dermatitis (AD) is a common inflammatory skin disease, and its pathogenesis is closely associated with microbial homeostasis in the gut, namely the gut-skin axis. Particularly, recent metagenomics studies revealed that the abundance of two major bacterial species in the gut, Faecalibacterium prausnitzii and Akkermansia muciniphila , may play a critical role in the pathogenesis of AD, but the effect of these species in AD has not yet been elucidated. To evaluate the potential beneficial effect of F. prausnitzii or A. muciniphila in AD, we conducted an animal model study where F. prausnitzii EB-FPDK11 or A. muciniphila EB-AMDK19, isolated from humans, was orally administered to 2,5-dinitrochlorobenzene (DNCB)-induced AD models using NC/Nga mice at a daily dose of 10 8 CFUs/mouse for six weeks. As a result, the administration of each strain of F. prausnitzii and A. muciniphila improved AD-related markers, such as dermatitis score, scratching behavior, and serum immunoglobulin E level. Also, the F. prausnitzii and A. muciniphila treatments decreased the level of thymic stromal lymphopoietin (TSLP), triggering the production of T helper (Th) 2 cytokines, and improved the imbalance between the Th1 and Th2 immune responses induced by DNCB. Meanwhile, the oral administration of the bacteria enhanced the production of filaggrin in the skin and ZO-1 in the gut barrier, leading to the recovery of functions. Taken together, our findings suggest that F. prausnitzii EB-FPDK11 and A. muciniphila EB-AMDK19 have a therapeutic potential in AD, which should be verified in humans.

The central amygdala (CeA) is a crucial hub in the processing of affective itch, containing a diverse array of neuronal populations. Among these components, Neuropeptide Y (NPY) and its receptors, such as NPY2R, affect various physiological and psychological processes. Despite this broad impact, the precise role of NPY2R + CeA neurons in itch modulation remains unknown, particularly concerning any potential lateralization effects. To address this, we employed optogenetics to selectively stimulate NPY2R + CeA neurons in mice, investigating their impact on itch modulation. Optogenetic activation of NPY2R + CeA neurons reduced scratching behavior elicited by pruritogens without exhibiting any lateralization effects. Electrophysiological recordings confirmed increased neuronal activity upon stimulation. However, this modulation did not affect thermal sensitivity, mechanical sensitivity, or formalin-induced hyperalgesia. Additionally, no alterations in anxiety-like behaviors or locomotion were observed upon stimulation. Projection tracing revealed connections of NPY2R + CeA neurons to brain regions implicated in itch processing. Overall, this comprehensive study highlights the role of NPY2R + CeA neurons in itch regulation without any lateralization effects.