The Dopaminergic Cells in the Median Raphe Region Regulate Social Behavior in Male Mice.

According to previous studies, the median raphe region (MRR) is known to contribute significantly to social behavior. Besides serotonin, there have also been reports of a small population of dopaminergic neurons in this region. Dopamine is linked to reward and locomotion, but very little is known about its role in the MRR. To address that, we first confirmed the presence of dopaminergic cells in the MRR of mice (immunohistochemistry, RT-PCR), and then also in humans (RT-PCR) using healthy donor samples to prove translational relevance. Next, we used chemogenetic technology in mice containing the Cre enzyme under the promoter of the dopamine transporter. With the help of an adeno-associated virus, designer receptors exclusively activated by designer drugs (DREADDs) were expressed in the dopaminergic cells of the MRR to manipulate their activity. Four weeks later, we performed an extensive behavioral characterization 30 min after the injection of the artificial ligand (Clozapine-N-Oxide). Stimulation of the dopaminergic cells in the MRR decreased social interest without influencing aggression and with an increase in social discrimination. Additionally, inhibition of the same cells increased the friendly social behavior during social interaction test. No behavioral changes were detected in anxiety, memory or locomotion. All in all, dopaminergic cells were present in both the mouse and human samples from the MRR, and the manipulation of the dopaminergic neurons in the MRR elicited a specific social response.

Revisiting the Role of Serotonin in Sleep-Disordered Breathing.

Serotonin or 5-hydroxytryptamine (5-HT) is a ubiquitous neuro-modulator-transmitter that acts in the central nervous system, playing a major role in the control of breathing and other physiological functions. The midbrain, pons, and medulla regions contain several serotonergic nuclei with distinct physiological roles, including regulating the hypercapnic ventilatory response, upper airway patency, and sleep-wake states. Obesity is a major risk factor in the development of sleep-disordered breathing (SDB), such as obstructive sleep apnea (OSA), recurrent closure of the upper airway during sleep, and obesity hypoventilation syndrome (OHS), a condition characterized by daytime hypercapnia and hypoventilation during sleep. Approximately 936 million adults have OSA, and 32 million have OHS worldwide. 5-HT acts on 5-HT receptor subtypes that modulate neural control of breathing and upper airway patency. This article reviews the role of 5-HT in SDB and the current advances in 5-HT-targeted treatments for SDB.

Median Raphe Nonserotonergic Neurons Modulate Hippocampal Theta Oscillations.

Hippocampal theta oscillations (HTOs) during rapid eye movement (REM) sleep play an important role in mnemonic processes by coordinating hippocampal and cortical activities. However, it is not fully understood how HTOs are modulated by subcortical regions, including the median raphe nucleus (MnR). The MnR is thought to suppress HTO through its serotonergic outputs. Here, our study on male mice revealed a more complex framework indicating roles of nonserotonergic MnR outputs in regulating HTO. We found that nonselective optogenetic activation of MnR neurons at theta frequency increased HTO amplitude. Granger causality analysis indicated that MnR theta oscillations during REM sleep influence HTO. By using three transgenic mouse lines, we found that MnR serotonergic neurons exhibited little or no theta-correlated activity during HTO. Instead, most MnR GABAergic neurons and Vglut3 neurons respectively increased and decreased activities during HTO and exhibited hippocampal theta phase-locked activities. Although MnR GABAergic neurons do not directly project to the hippocampus, they could modulate HTO through local Vglut3 and serotonergic neurons as we found that MnR GABAergic neurons monosynaptically targeted Vglut3 and serotonergic neurons. Additionally, pontine wave recorded from the MnR during REM sleep accompanied nonserotonergic activity increase and HTO acceleration. These results suggest that MnR nonserotonergic neurons modulate hippocampal theta activity during REM sleep, which regulates memory processes.SIGNIFICANCE STATEMENT The MnR is the major source of serotonergic inputs to multiple brain regions including the hippocampus and medial septal area. It has long been thought that those serotonergic outputs suppress HTOs. However, our results revealed that MnR serotoninergic neurons displayed little firing changes during HTO. Instead, MnR Vglut3 neurons were largely silent during HTO associated with REM sleep. Additionally, many MnR GABAergic neurons fired rhythmically phase-locked to HTO. These results indicate an important role of MnR nonserotonergic neurons in modulating HTO.

Projection-defined median raphe Pet+ subpopulations are diversely implicated in seizure.

The raphe nuclei, the primary resource of forebrain 5-HT, play an important but heterogeneous role in regulating subcortical excitabilities. Fundamental circuit organizations of different median raphe (MR) subsystems are far from completely understood. In the present study, using cell-specific viral tracing, Ca2+ fiber photometry and epilepsy model, we map out the forebrain efferent and afferent of different MR Pet+ subpopulations and their divergent roles in epilepsy. We found that PetMR neurons send both collateral and parallel innervations to different downstream regions through different subpopulations. Notably, CA3-projecting PetMR subpopulations are largely distinct from habenula (Hb)-projecting PetMR subpopulations in anatomical distribution and topological organization, while majority of the CA3-projecting PetMR subpopulations are overlapped with the medial septum (MS)-projecting PetMR subpopulations. Further, using Ca2+ fiber photometry, we monitor activities of PetMR neurons in hippocampal-kindling seizure, a classical epilepsy model with pathological mechanisms caused by excitation-inhibition imbalance. We found that soma activities of PetMR neurons are heterogeneous during different periods of generalized seizures. These divergent activities are contributed by different projection-defined PetMR subpopulations, manifesting as increased activities in CA3 but decreased activity in Hb resulting from their upstream differences. Together, our findings provide a novel framework of MR subsystems showing that projection-defined MR Pet+ subpopulations are topologically heterogenous with divergent circuit connections and are diversely implicated in seizures. This may help in the understanding of heterogeneous nature of MR 5-HTergic subsystems and the paradox roles of 5-HTergic systems in epilepsy.

Median raphe cysts: A clinico-pathologic and immunohistochemical study of 52 cases.

BACKGROUND: Median raphe cysts (MRC) are epithelial-lined cystic lesions of the genital area that do not communicate with the urethra or the overlying epidermis. Immunohistochemically, MRC show positivity for cytokeratin (CK) 5-6, CK 7, carcinoembryonic antigen, p63 and uroplakin III (URO III). GATA3 and human milk fat globulin 1 (HMFG1) are immunohistochemical markers that have been not previously studied in MRC. METHODS: We conducted a study of 52 patients diagnosed with MRC in the Pathology Departments of eight hospitals between 1990 and 2016. The monoclonal antibodies used were CK5-6, CK7, CK20, URO III, p63, GATA3, and HMFG1. HMFG1 was studied in five cases of apocrine hidrocystomas and compared with five cases of MRC from our series. RESULTS: CK 5-6, CK7, and p63 expression showed strong positivity in the urothelial epithelium of 48 cases. CK20 was focally positive in areas of mucinous differentiation in three cases. GATA3 showed intense nuclear staining in 30 cases. HMFG1 was positive in three cases of MRC and in three cases of apocrine hidrocystoma. CONCLUSION: Positivity of GATA3 and CK7 in MRC supports the urothelial origin of these cysts. We found no differences in HMFG1 expression between MRC and apocrine hidrocystomas.

Neurochemically and Hodologically Distinct Ascending VGLUT3 versus Serotonin Subsystems Comprise the r2-Pet1 Median Raphe.

Brainstem median raphe (MR) neurons expressing the serotonergic regulator gene Pet1 send collateralized projections to forebrain regions to modulate affective, memory-related, and circadian behaviors. Some Pet1 neurons express a surprisingly incomplete battery of serotonin pathway genes, with somata lacking transcripts for tryptophan hydroxylase 2 (Tph2) encoding the rate-limiting enzyme for serotonin [5-hydroxytryptamine (5-HT)] synthesis, but abundant for vesicular glutamate transporter type 3 (Vglut3) encoding a synaptic vesicle-associated glutamate transporter. Genetic fate maps show these nonclassical, putatively glutamatergic Pet1 neurons in the MR arise embryonically from the same progenitor cell compartment-hindbrain rhombomere 2 (r2)-as serotonergic TPH2+ MR Pet1 neurons. Well established is the distribution of efferents en masse from r2-derived, Pet1-neurons; unknown is the relationship between these efferent targets and the specific constituent source-neuron subgroups identified as r2-Pet1Tph2-high versus r2-Pet1Vglut3-high Using male and female mice, we found r2-Pet1 axonal boutons segregated anatomically largely by serotonin+ versus VGLUT3+ identity. The former present in the suprachiasmatic nucleus, paraventricular nucleus of the thalamus, and olfactory bulb; the latter are found in the hippocampus, cortex, and septum. Thus r2-Pet1Tph2-high and r2-Pet1Vglut3-high neurons likely regulate distinct brain regions and behaviors. Some r2-Pet1 boutons encased interneuron somata, forming specialized presynaptic "baskets" of VGLUT3+ or VGLUT3+/5-HT+ identity; this suggests that some r2-Pet1Vglut3-high neurons may regulate local networks, perhaps with differential kinetics via glutamate versus serotonin signaling. Fibers from other Pet1 neurons (non-r2-derived) were observed in many of these same baskets, suggesting multifaceted regulation. Collectively, these findings inform brain organization and new circuit nodes for therapeutic considerations.SIGNIFICANCE STATEMENT Our findings match axonal bouton neurochemical identity with distant cell bodies in the brainstem raphe. The results are significant because they suggest that disparate neuronal subsystems derive from Pet1+ precursor cells of the embryonic progenitor compartment rhombomere 2 (r2). Of these r2-Pet1 neuronal subsystems, one appears largely serotonergic, as expected given expression of the serotonergic regulator PET1, and projects to the olfactory bulb, thalamus, and suprachiasmatic nucleus. Another expresses VGLUT3, suggesting principally glutamate transmission, and projects to the hippocampus, septum, and cortex. Some r2-Pet1 boutons-those that are VGLUT3+ or VGLUT3+/5-HT+ co-positive-comprise "baskets" encasing interneurons, suggesting that they control local networks perhaps with differential kinetics via glutamate versus serotonin signaling. Results inform brain organization and circuit nodes for therapeutic consideration.

Concurrent brain structural and functional alterations in patients with migraine without aura: an fMRI study.

OBJECTIVES: To explore the possible concurrent brain functional and structural alterations in patients with migraine without aura (MwoA) patients compared to healthy subjects (HS). METHODS: Seventy-two MwoA patients and forty-six HS were recruited. 3D-T1 and resting state fMRI data were collected during the interictal period for MwoA and HS. Voxel-based morphometry (VBM) for structure analysis and regional homogeneity (Reho) for fMRI analysis were applied. The VBM and Reho maps were overlapped to determine a possible brain region with concurrent functional and structural alteration in MwoA patients. Further analysis of resting state functional connectivity (FC) alteration was applied with this brain region as the seed. RESULTS: Compared with HS, MwoA patients showed decreased volume in the bilateral superior and inferior colliculus, periaqueductal gray matter (PAG), locus ceruleus, median raphe nuclei (MRN) and dorsal pons medulla junction. MwoA patients showed decreased Reho values in the middle occipital gyrus and inferior occipital gyrus, and increased Reho values in the MRN. Only a region in the MRN showed both structural and functional alteration in MwoA patients. Pearson correlation analysis showed that there was no association between volume or Reho values of the MRN and headache frequency, headache intensity, disease duration, self-rating anxiety scale or self-rating depression scale in MwoA patients. Resting state functional connectivity (FC) with the MRN as the seed showed that MwoA patients had increased FC between the MRN and PAG. CONCLUSIONS: MRN are involved in the pathophysiology of migraine during the interictal period. This study may help to better understand the migraine symptoms. TRIAL REGISTRATION: NCT01152632 . Registered 27 June 2010.

Serotonin 5-HT4 Receptor Agonists Improve Facilitation of Contextual Fear Extinction in an MPTP-Induced Mouse Model of Parkinson's Disease.

Previously, we found that 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson's disease (PD) model mice (PD mice) showed facilitation of hippocampal memory extinction via reduced cyclic adenosine monophosphate (cAMP)/cAMP-dependent response element-binding protein (CREB) signaling, which may cause cognitive impairment in PD. Serotonergic neurons in the median raphe nucleus (MnRN) project to the hippocampus, and functional abnormalities have been reported. In the present study, we investigated the effects of the serotonin 5-HT4 receptor (5-HT4R) agonists prucalopride and velusetrag on the facilitation of memory extinction observed in PD mice. Both 5-HT4R agonists restored facilitation of contextual fear extinction in PD mice by stimulating the cAMP/CREB pathway in the dentate gyrus of the hippocampus. A retrograde fluorogold-tracer study showed that γ-aminobutyric acid-ergic (GABAergic) neurons in the reticular part of the substantia nigra (SNr), but not dopaminergic (DAergic) neurons in the substantia nigra pars compacta (SNpc), projected to serotonergic neurons in the MnRN, which are known to project their nerve terminals to the hippocampus. It is possible that the degeneration of the SNpc DAergic neurons in PD mice affects the SNr GABAergic neurons, and thereafter, the serotonergic neurons in the MnRN, resulting in hippocampal dysfunction. These findings suggest that 5HT4R agonists could be potentially useful as therapeutic drugs for treating cognitive deficits in PD.

[Linear cystic lesion of the median raphe in an 11-year-old child]. / Lésion linéaire kystique du raphé médian chez un enfant de 11 ans.

BACKGROUND: Median raphe cysts are rare benign lesions of the male genitalia. They may be present along the entire raphe, from the urethral meatus to the anus, in the median position. We report herein a case of median raphe cyst with an atypical clinical and histological presentation. PATIENTS AND METHODS: An 11-year-old boy consulted in dermatology for an asymptomatic perineal lesion. The clinical examination revealed a linear cystic lesion with clear content extending from the base of the scrotum to the anus. The histological diagnosis was a superficial dermal glandular cyst suggestive of a possibly apocrine origin in this topography, or possibly due to malformation. DISCUSSION: Different clinical and histological features of median raphe cysts have been reported in the literature. Treatment is mainly surgical.

Will imaging individual raphe nuclei in males with major depressive disorder enhance diagnostic sensitivity and specificity?

BACKGROUND: Positron emission tomography (PET) studies in major depressive disorder (MDD) have reported higher serotonin 1A (5-HT1A ) autoreceptor binding in the raphe. In males, the difference is so large that it can potentially be used as the first biological marker for MDD. However, the raphe includes several nuclei, which project to different regions of the brain and spinal cord and may be differentially involved in disease. We aimed to identify 5-HT1A differences in individual raphe nuclei using PET in order to determine whether use of subnuclei would provide greater sensitivity and specificity of diagnosing MDD. METHODS: We identified individual nuclei using a hybrid set-level technique on an average [11 C]-WAY100635 PET image derived from 52 healthy volunteers (HV). We delineated three nuclei: dorsal raphe nucleus (DRN), median raphe nucleus (MRN), and raphe magnus (RMg). An atlas image of these nuclei was created and nonlinearly warped to each subject (through an associated MRI) in a separate sample of 41 males (25 HV, 16 MDD) who underwent [11 C]-WAY100635 PET. RESULTS: 5-HT1A binding was elevated in DRN in MDD (P < .01), and was not different in the RMg and MRN between groups. Receiver operating characteristic (ROC) curves showed that combining DRN and MRN produces highest sensitivity (94%) and specificity (84%) to identify MDD. CONCLUSION: In agreement with postmortem studies, we found higher 5-HT1A autoreceptor binding in MDD selectively in the DRN. 5-HT1A autoreceptor binding in the combined DRN and MRN is a better biomarker for MDD than in the raphe as a whole.

Deep brain stimulation for the treatment of disorders of consciousness and cognition in traumatic brain injury patients: a review.

Traumatic brain injury (TBI) is a looming epidemic, growing most rapidly in the elderly population. Some of the most devastating sequelae of TBI are related to depressed levels of consciousness (e.g., coma, minimally conscious state) or deficits in executive function. To date, pharmacological and rehabilitative therapies to treat these sequelae are limited. Deep brain stimulation (DBS) has been used to treat a number of pathologies, including Parkinson disease, essential tremor, and epilepsy. Animal and clinical research shows that targets addressing depressed levels of consciousness include components of the ascending reticular activating system and areas of the thalamus. Targets for improving executive function are more varied and include areas that modulate attention and memory, such as the frontal and prefrontal cortex, fornix, nucleus accumbens, internal capsule, thalamus, and some brainstem nuclei. The authors review the literature addressing the use of DBS to treat higher-order cognitive dysfunction and disorders of consciousness in TBI patients, while also offering suggestions on directions for future research.

Canaliform median raphe cysts (MRCs) lined by squamous epithelium in a 5 year old male patient; report of a rare case and comprehensive review of the literature.

Median raphe cysts (MRCs) are rare, benign congenital lesions of unknown origin, that can be found anywhere on the ventral side of the genital area, between the urethral meatus and the anus. The rarity of our case is attributed to the canaliform type, the scrotal and perineal localization and the epidermoid epithelium. A 5 year old boy, with free perinatal and family history, was admitted to our department as an outpatient due to the presence of an elongated and mildly painful lesion in the middle of the scrotum, gradually increasing in size. During physical examination the presence of a painful, subcutaneous, yellowish lesion, extending from the scrotal to the perineal raphe, was documented. Patient underwent elective surgery, under general endotracheal anesthesia, and complete resection of the lesion was conducted. Histopathological examination revealed the presence of a canaliform lesion consisting of five cysts, lined by squamous epithelium and filled with lamellate keratin. IN CONCLUSION: a) preventive removal of MRCs is considered as the safest treatment option, in order to be avoided future, potential complications regarding urination and sexual intercourse, b) if therapeutic intervention is delayed, especially a er development of inflammation of MRCs, then the likelihood both of iatrogenic injury to underlying structures, mainly to the penile or perineal urethra, and of relapse a er resection increases significantly and c) if orchidopexy precedes the development of MRCs, the possibility of presence of ovarian serous border line tumor with Müllerian duct remnants should always be excluded.

Median raphe stimulation-induced motor inhibition concurrent with suppression of type 1 and type 2 hippocampal theta.

This study investigated behavioral, anatomical and electrophysiological effects produced by electrical stimulation of posterior hypothalamic (PH) or median raphe (MR) nuclei, independently and during combined stimulation of both PH and MR. These three stimulation conditions were applied during spontaneous behavior in an open field and during PH stimulation-induced wheel running, while simultaneously recording hippocampal (HPC) field activity. An additional objective was to determine the effects of MR stimulation on Type 1 movement related theta and Type 2 sensory processing related theta. To achieve the latter, when behavioral studies were completed we studied the same rats under urethane anesthesia and then during urethane anesthesia with the addition of atropine sulfate (ATSO4). Here we demonstrated that electrical stimulation of a localized region of the MR nucleus resulted in a profound inhibition of both spontaneously occurring theta related motor behaviors and the theta related motor behaviors induced by electrical stimulation of the PH nucleus. Furthermore, this motor inhibition occurred concurrently with strong suppression of hippocampal theta field oscillations in the freely moving rat, a condition where the theta recorded is Type 2 sensory processing theta occurring coincidently with Type 1 movement related theta (Bland, 1986). Our results indicate that motor inhibition resulted from stimulation of neurons located in the mid central region of the MR, while stimulation in adjacent regions produced variable responses, including movements and theta activity. The present study provided evidence that the pharmacological basis of the suppression of Type 2 sensory processing HPC theta was cholinergic. However, MR inhibition of PH-induced wheel running was not affected by cholinergic blockade, which blocks Type 2 theta, indicating that MR stimulation-induced motor inhibition also requires the suppression of Type 1 theta.

[Abnormalities of the male median raphe]. / Anomalies du raphé médian chez l'homme.

INTRODUCTION: Abnormalities of the male median raphe can either be detected during postnatal examination or appear later during childhood or adulthood. They can be isolated or sometimes associated with severe congenital genitourinary malformations. METHODS: A literature review was performed on the Medline database, considering the articles listed until April 2015 dealing with abnormalities of the male median raphe using the following keywords: male, median raphe and abnormalities. Papers were selected according to their language (English and French) and their relevance. RESULTS: Forty-one articles related to male median raphe abnormalities were listed. Five of them were selected for their relevance. We describe frequent median raphe abnormalities (hyperpigmentation, deviation, division, cyst, canal and sinus), emphasizing the clinical aspects, the explorations, the risk of associated genitourinary abnormalities and the treatment. DISCUSSION: Male raphe abnormalities should be known by the urologists since functional, infectious and aesthetic complications could lead patients to consultation.

Functional connectivity of the dorsal and median raphe nuclei at rest.

Serotonin (5-HT) is a neurotransmitter critically involved in a broad range of brain functions and implicated in the pathophysiology of neuropsychiatric illnesses including major depression, anxiety and sleep disorders. Despite being widely distributed throughout the brain, there is limited knowledge on the contribution of 5-HT to intrinsic brain activity. The dorsal raphe (DR) and median raphe (MR) nuclei are the source of most serotonergic neurons projecting throughout the brain and thus provide a compelling target for a seed-based probe of resting-state activity related to 5-HT. Here we implemented a novel multimodal neuroimaging approach for investigating resting-state functional connectivity (FC) between DR and MR and cortical, subcortical and cerebellar target areas. Using [(11)C]DASB positron emission tomography (PET) images of the brain serotonin transporter (5-HTT) combined with structural MRI from 49 healthy volunteers, we delineated DR and MR and performed a seed-based resting-state FC analysis. The DR and MR seeds produced largely similar FC maps: significant positive FC with brain regions involved in cognitive and emotion processing including anterior cingulate, amygdala, insula, hippocampus, thalamus, basal ganglia and cerebellum. Significant negative FC was observed within pre- and postcentral gyri for the DR but not for the MR seed. We observed a significant association between DR and MR FC and regional 5-HTT binding. Our results provide evidence for a resting-state network related to DR and MR and comprising regions receiving serotonergic innervation and centrally involved in 5-HT related behaviors including emotion, cognition and reward processing. These findings provide a novel advance in estimating resting-state FC related to 5-HT signaling, which can benefit our understanding of its role in behavior and neuropsychiatric illnesses.

Clinicopathological features and histogenesis of penile cysts.

Cysts arising in the penis are uncommon and can be found anywhere from the urethral meatus to the root of the penis involving glans, foreskin, or shaft. Median raphe cysts account for the majority of penile cystic lesions reported in the literature. As their name suggests, they arise on the ventral midline of the penis that extends from the urethral meatus to the scrotum and perineum. Proposed hypotheses for their origin as well as their diverse morphology are discussed.

The serotonergic neurons derived from rhombomere 2 are localized in the median raphe and project to the dorsal pallium in zebrafish.

The serotonergic neurons in the raphe nucleus are implicated in various cognitive functions such as learning and emotion. In vertebrates, the raphe nucleus is divided into the dorsal raphe and the median raphe. In contrast to the abundance of knowledge on the functions of the dorsal raphe, the roles of the serotonergic neurons in the median raphe are relatively unknown. The studies using zebrafish revealed that the median raphe serotonergic neurons receive input from the two distinct pathways from the habenula and the IPN. The use of zebrafish may reveal the function of the Hb-IPN-median raphe pathway. To clarify the functions of the median raphe serotonergic neurons, it is necessary to distinguish them from those in the dorsal raphe. Most median raphe serotonergic neurons originate from rhombomere 2 in mice, and we generated the transgenic zebrafish which can label the serotonergic neurons derived from rhombomere 2. In this study, we found the serotonergic neurons derived from rhombomere 2 are localized in the median raphe and project axons to the rostral dorsal pallium in zebrafish. This study suggests that this transgenic system has the potential to specifically reveal the function and information processing of the Hb-IPN-raphe-telencephalon circuit in learning.

Manipulation of Glutamatergic Neuronal Activity in the Primary Motor Cortex Regulates Cardiac Function in Normal and Myocardial Infarction Mice.

Cardiac function is under neural regulation; however, brain regions in the cerebral cortex responsible for regulating cardiac function remain elusive. In this study, retrograde trans-synaptic viral tracing is used from the heart to identify a specific population of the excitatory neurons in the primary motor cortex (M1) that influences cardiac function in mice. Optogenetic activation of M1 glutamatergic neurons increases heart rate, ejection fraction, and blood pressure. By contrast, inhibition of M1 glutamatergic neurons decreased cardiac function and blood pressure as well as tyrosine hydroxylase (TH) expression in the heart. Using viral tracing and optogenetics, the median raphe nucleus (MnR) is identified as one of the key relay brain regions in the circuit from M1 that affect cardiac function. Then, a mouse model of cardiac injury is established caused by myocardial infarction (MI), in which optogenetic activation of M1 glutamatergic neurons impaired cardiac function in MI mice. Moreover, ablation of M1 neurons decreased the levels of norepinephrine and cardiac TH expression, and enhanced cardiac function in MI mice. These findings establish that the M1 neurons involved in the regulation of cardiac function and blood pressure. They also help the understanding of the neural mechanisms underlying cardiovascular regulation.

The Role of Vesicular Glutamate Transporter Type 3 in Social Behavior, with a Focus on the Median Raphe Region.

Social behavior is important for our well-being, and its dysfunctions impact several pathological conditions. Although the involvement of glutamate is undeniable, the relevance of vesicular glutamate transporter type 3 (VGluT3), a specific vesicular transporter, in the control of social behavior is not sufficiently explored. Since midbrain median raphe region (MRR) is implicated in social behavior and the nucleus contains high amount of VGluT3+ neurons, we compared the behavior of male VGluT3 knock-out (KO) and VGluT3-Cre mice, the latter after chemogenetic MRR-VGluT3 manipulation. Appropriate control groups were included. Behavioral test battery was used for social behavior (sociability, social discrimination, social interaction, resident intruder test) and possible confounding factors (open field, elevated plus maze, Y-maze tests). Neuronal activation was studied by c-Fos immunohistochemistry. Human relevance was confirmed by VGluT3 gene expression in relevant human brainstem areas. VGluT3 KO mice exhibited increased anxiety, social interest, but also aggressive behavior in anxiogenic environment and impaired social memory. For KO animals, social interaction induced lower cell activation in the anterior cingulate, infralimbic cortex, and medial septum. In turn, excitation of MRR-VGluT3+ neurons was anxiolytic. Inhibition increased social interest 24 h later but decreased mobility and social behavior in aggressive context. Chemogenetic activation increased the number of c-Fos+ neurons only in the MRR. We confirmed the increased anxiety-like behavior and impaired memory of VGluT3 KO strain and revealed increased, but inadequate, social behavior. MRR-VGluT3 neurons regulated mobility and social and anxiety-like behavior in a context-dependent manner. The presence of VGluT3 mRNA on corresponding human brain areas suggests clinical relevance.

Preputial cyst in the newborn: A case report from Africa.

Cysts of the prepuce are rare, and documented reports from the English literature are mostly from Asia. Presentations in children are worrisome to the parents. We report a case of a preputial cyst occurring in a neonate who was brought to our facility due to parental anxiety. After a thorough clinical evaluation, a freehand circumcision technique was performed which allowed exposure of the full extent of the cyst, the external urethral meatus and the glans, thus ensuring complete excision and minimising the risk of injury to the adjoining structures. We postulate that preputial cysts are rare in Africa due to the universality of circumcision, which is one of the options of treatment. Preputial cysts are benign foreskin cystic lesions that can be effectively treated with circumcision. This is probably the first reported case of a benign epithelioid preputial cyst from Africa. The paucity of reported cases may be due to the universal practice of circumcision in most of Africa.