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Social memory, the ability to recognize and remember individuals within a social group, is crucial for social interactions and relationships. Deficits in social memory have been linked to several neuropsychiatric and neurodegenerative disorders. The hippocampus, especially the circuit that links dorsal CA2 and ventral CA1 neurons, is considered a neural substrate for social memory formation. Recent studies have provided compelling evidence of extrahippocampal contributions to social memory. The septal nuclei, including the medial and lateral septum, make up a basal forebrain region that shares bidirectional neuronal connections with the hippocampus and has recently been identified as critical for social memory. The focus of our review is the neural circuit mechanisms that underlie social memory, with a special emphasis on the septum. We also discuss the social memory dysfunction associated with neuropsychiatric and neurodegenerative disorders. [ABSTRACT FROM AUTHOR]

Introduction: Septum pellucidum pilocytic astrocytoma is rare. There are only 3 reported cases in literature. Our patient is the fourth case. Case presentation: A 17-year-old male presented with headache. CT brain and MRI brain showed septum pellucidum lesion with obstructive hydrocephalus which looked like colloid cyst. Intraoperatively, the tumor was attached to the lower part of septum pellucidum and it didn't look like a colloid cyst. Histopathology was pilocytic astrocytoma. Postoperatively, patient recovered well with no neurological deficits or adverse neurological sequalae. Conclusion: Septum pellucidum pilocytic astrocytoma should be considered as one of the differential diagnosis of septum pellucidum tumors. We observed that the interhemispheric transcallosal transventricular approach might be associated with lesser comorbidities and neurological deficits in tumors in this location. [ABSTRACT FROM AUTHOR]

Aims: Diastolic dysfunction represents the earliest and most common manifestation of diabetic cardiomyopathy. Nitric oxide (NO), a potent vasodilator and anti-inflammatory mediator released from the subendocardial and coronary endothelium, favors left ventricular distensibility and relaxation. In type 2 diabetes (T2D), the NO bioavailability is reduced due to the oxidative stress and inflammatory state of the endothelium, because of chronic hyperglycemia. The aim of the present research is to evaluate the relationship between endothelial function and diastolic function in subjects with T2D. Method: Subjects with T2D and age and sex-matched healthy controls were consecutively recruited. All participants underwent flow-mediated dilation (FMD) to assess endothelial function, and echocardiography to evaluate diastolic function. Results: Thirty-five patients (6 women, 29 men) and 35 healthy controls were included in the final analysis. FMD was significantly lower in T2D than controls (4.4 ± 3.4 vs. 8.5 ± 4.3%, p = 0.001). T2D presented different abnormalities in diastolic function compared to controls: lower E/A (early to late diastolic transmitral flow velocity), lower septal and lateral e′ (early diastolic myocardial tissue velocity at septum and lateral wall), and higher E/e′ (surrogate of filling pressure). In subjects with T2D, we observed a significant correlation between FMD and E/e′ (r = −0.63, p = 0.001), lateral e′ (r = 0.44, p = 0.03), and septal e′ (r = 0.39, p = 0.05). Conclusions: Our observational study demonstrated a link between FMD and diastolic dysfunction in subjects with type 2 diabetes. [ABSTRACT FROM AUTHOR]

• This is the first study to examine how the microbiome interacts with aggression through urine profiling. This analysis was particularly nuanced because not only did we compare basal urine metabolomes in response to microbiota manipulation (four unique study groups, above), but we also capture real-time metabolic responses to aggressive interactions by comparing samples taken before and after behavioral assays. • Here, we expanded the study of brain function in the aggression-microbiota interplay, quantifying serotonin, serotonin turnover and tryptophan levels using HPLC as well as identifying key gene expression patterns using transcriptomics in five different regions of the brain. We examined gene expression related to serotonin and other neurotransmitter receptors in multiple brain regions, identifying the septum as an important brain region for regulation of aggression. Gene set enrichment analysis was also used to highlight other, less studied pathways (Rho GTPase and Reelin) associated with aggressive behavior in the context of the gut-brain-microbiome axis. • The data generated in this study is rich (untargeted metabolomics of urine and transcriptomics of five brain regions), spanning four microbiota manipulation states, and will be publicly available , further extending the potential application of our research. • We include a study of humanized mice using unique fecal samples of 1-month-old infants, collected nearly a month after early-life ABX administration. In previous work (Uzan-Yulzari et al. 2021 , Nat Comm), we have demonstrated that ABX in this critical period of life can have lasting effects of childhood growth. Here, we extend these findings using samples from the same cohort. Using fecal samples collected weeks after ABX administration also reduces the direct chemical effects of ABX on the host, highlighting the causative role of the dysbiotic host microbiome and associated metabolome in driving aggressive behavior. We demonstrate that infant microbiota, perturbed within the first 48 h of life, has a lasting signature through 1 month of age that, when transplanted into GF mice, results in increased aggression (3 – 5 weeks after transplant) when compared to effects of stools of infants not exposed to any early-life antibiotics. The findings are revolutionary as they show how ABX-altered microbiota during a critical development window can lead to persisting behavioral deficits. Recent research has unveiled conflicting evidence regarding the link between aggression and the gut microbiome. Here, we compared behavior profiles of control, germ-free (GF), and antibiotic-treated mice, as well as re-colonized GF mice to understand the impact of the gut microbiome on aggression using the resident-intruder paradigm. Our findings revealed a link between gut microbiome depletion and higher aggression, accompanied by notable changes in urine metabolite profiles and brain gene expression. This study extends beyond classical murine models to humanized mice to reveal the clinical relevance of early-life antibiotic use on aggression. Fecal microbiome transplant from infants exposed to antibiotics in early life (and sampled one month later) into mice led to increased aggression compared to mice receiving transplants from unexposed infants. This study sheds light on the role of the gut microbiome in modulating aggression and highlights its potential avenues of action, offering insights for development of therapeutic strategies for aggression-related disorders. [ABSTRACT FROM AUTHOR]

Liraglutide, a glucagon-like peptide-1 (GLP-1) analog, is approved for obesity treatment, but the specific neuronal sites that contribute to its therapeutic effects remain elusive. Here, we show that GLP-1 receptor-positive (GLP-1R-positive) neurons in the lateral septum ( LSGLP-1R) play a critical role in mediating the anorectic and weight-loss effects of liraglutide. LSGLP-1R neurons were robustly activated by liraglutide, and chemogenetic activation of these neurons dramatically suppressed feeding. Targeted knockdown of GLP-1 receptors within the LS, but not in the hypothalamus, substantially attenuated liraglutide’s ability to inhibit feeding and lower body weight. The activity of LSGLP-1R neurons rapidly decreased during naturalistic feeding episodes, while synaptic inactivation of LSGLP-1R neurons diminished the anorexic effects triggered by liraglutide. Together, these findings offer critical insights into the functional role of LSGLP-1R neurons in the physiological regulation of energy homeostasis and delineate their instrumental role in mediating the pharmacological efficacy of liraglutide. [ABSTRACT FROM AUTHOR]

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In bone regeneration, synthetic materials are required to replace autogenous bone grafts. The shape, composition, surface, and porous structure of the material are key factors in bone formation and material resorption. In this study, we describe the fabrication of Mg-doped biphasic calcium phosphate (Mg-BCP) granules comprising hydroxyapatite (HAp) and beta-tricalcium phosphate (β-TCP) by exploiting the structural and chemical characteristics of sea urchin spines. The Mg-BCP granules were cylinders with a 1.2–1.8 mm diameter and height of 1.4–1.7 mm. The β-TCP/HAp ratio and Mg content in the Mg-BCP granules were controlled within the ranges of 0.36–0.45 and 2.40–6.21 mol%, respectively. Controlling the β-TCP/HAp ratio and Mg content may contribute to controlling the material resorption rate and promoting osteogenesis and angiogenesis. The Mg-BCP granules maintained the structural characteristics of the sea urchin spines. The granules comprised radial wedges termed septa, and a meshwork termed stereom. The interseptal gaps, or micropores, decreased from the granular exterior (24–29 μm) to the interior (14–28 μm). The septa in the outermost layer provide concavities on the sides of the cylindrical granules. The stereom meshworks in the core and outer layers involved micropores in the ranges of 3–15 and 3–10 μm, respectively. These multiscale pores and surface undulations may improve cell penetration and attachment, bodily fluid permeability, and protein adsorption. The compressive strengths of the Mg-BCP granules were in the range of 45.2–46.1 MPa, which are useful as bone grafts. Due to their rounded shapes, the Mg-BCP granules filled a mold more densely than the clinically used and irregularly shaped granules. These findings demonstrated that Mg-BCP granules are promising materials for bone regeneration. [ABSTRACT FROM AUTHOR]

Fear memory is essential for survival and adaptation, yet excessive fear memories can lead to emotional disabilities and mental disorders. Despite previous researches have indicated that histamine H1 receptor (H1R) exerts critical and intricate effects on fear memory, the role of H1R is still not clarified. Here, we show that deletion of H1R gene in medial septum (MS) but not other cholinergic neurons selectively enhances contextual fear memory without affecting cued memory by differentially activating the dentate gyrus (DG) neurons in mice. H1R in cholinergic neurons mediates the contextual fear retrieval rather than consolidation by decreasing acetylcholine release pattern in DG. Furthermore, selective knockdown of H1R in the MS is sufficient to enhance contextual fear memory by manipulating the retrieval-induced neurons in DG. Our results suggest that H1R in MS cholinergic neurons is critical for contextual fear retrieval, and could be a potential therapeutic target for individuals with fear-related disorders. Neural mechanism underlying fear memory process is not fully understood. Here, the authors report that histamine H1 receptor (H1R) in medial septum cholinergic neurons is critical for contextual fear retrieval, serving as a promising target for related neurological disease. [ABSTRACT FROM AUTHOR]

Introduction: In nurturing systems, the oxytocin (Oxt)-oxytocin receptor (Oxtr) system is important for parturition, and essential for lactation and parental behavior. Among the nerve nuclei that express Oxtr, the lateral septal nucleus (LS) and medial preoptic area (MPOA) are representative regions that control maternal behavior. Methods: We investigated the role of Oxtr- and Oxtr-expressing neurons, located in the LS and MPOA, in regulating maternal behavior by regulating Oxtr expression in a region-specific manner using recombinant mice and adeno-associated viruses. We quantified the prolactin (Prl) concentrations in the pituitary gland and plasma when Oxtr expression in the MPOA was reduced. Results: The endogenous Oxtr gene in the neurons of the LS did not seem to play an essential role in maternal behavior. Conversely, decreased Oxtr expression in the MPOA increased the frequency of pups being left outside the nest and reduced their survival rate. Deletion of Oxtr in MPOA neurons prevented elevation of Prl levels in plasma and pituitary at postpartum day 2. Discussion/Conclusion: Oxtr-expressing neurons in the MPOA are involved in the postpartum production of Prl. We confirmed the essential functions of Oxtr-expressing neurons and the Oxtr gene itself in the MPOA for the sustainability of maternal behavior, which involved Oxtr-dependent induction of Prl. [ABSTRACT FROM AUTHOR]

Background: Congenital anomalies in dogs are the defects present at birth and often lead to perinatal death if it involves any vital organ or system like cardiovascular system. Some dogs may remain asymptomatic or may have non cardiac manifestations and hence, undetected until later in life, so the percentage of dogs with congenital heart diseases that survive to adulthood can be rather high. Atrial septal defect (ASD) is an unusual congenital heart disease in dogs that is characterized by communication between the two atria due to a defect in the interatrial septum. Methods: A thorough clinical examination followed by physical examination, thoracic radiography and 2d-echocardiography was performed to determine the septal defect. Doppler evaluation of ASD dogs was carried out to confirm the blood flow direction through the septal defect, which was managed medically. Result: In the present study, ASD (secundum type) was diagnosed in 7dogs (7.5%) aged between 2y-6y. Boxer, German shepherd, Cocker spaniel, Daschund and Pomeranian were the breeds affected. Soft systolic murmur on left heart base and pulmonic valve area, low intensity heart sounds, distended jugular vein, jugular pulse and ascites were the significant findings on physical examination. Though few dogs (21%) were asymptomatic, exercise intolerance, dyspnoea, general weakness, cough and syncope were the presenting signs among other cases. Enlarged right heart, pleural effusion and pulmonary overcirculation were radiographic findings. 2d-echocardiographic evaluation determined the presence of the defect as a loss of echogenicity at the interatrial septum and presence of interatrial communication of varied size, enlargement of main pulmonary artery and thick atrio-ventricular valves but with normal left atrium:aorta base ratio, increased fractional shortening, systolic function and paradoxal septal motion. The colour flow Doppler study demonstrated a continuous flow with left-to-right shunt. [ABSTRACT FROM AUTHOR]

Spatial memory encoding depends in part on cholinergic modulation. How acetylcholine supports spatial memory encoding is not well understood. Prior studies indicate that acetylcholine release is correlated with exploration, including epochs of rearing onto hind legs. Here, to test whether elevated cholinergic tone increases the probability of rearing, we tracked rearing frequency and duration while optogenetically modulating the activity of choline acetyltransferase containing (i.e., acetylcholine producing) neurons of the medial septum in rats performing a spatial working memory task (n = 17 rats). The cholinergic neurons were optogenetically inhibited using halorhodopsin for the duration that rats occupied two of the four open arms during the study phase of an 8‐arm radial arm maze win‐shift task. Comparing rats' behaviour in the two arm types showed that rearing frequency was not changed, but the average duration of rearing epochs became significantly longer. This effect on rearing was observed during optogenetic inhibition but not during sham inhibition or in rats that received infusions of a fluorescent reporter virus (i.e., without halorhodopsin; n = 6 rats). Optogenetic inhibition of cholinergic neurons during the pretrial waiting phase had no significant effect on rearing, indicating a context‐specificity of the observed effects. These results are significant in that they indicate that cholinergic neuron activity in the medial septum is correlated with rearing not because it motivates an exploratory state but because it contributes to the processing of information acquired while rearing. [ABSTRACT FROM AUTHOR]

Deficits in hippocampus‐dependent memory processes are common across psychiatric and neurodegenerative disorders such as depression, anxiety and Alzheimer's disease. Moreover, stress is a major environmental risk factor for these pathologies and it exerts detrimental effects on hippocampal functioning via the activation of hypothalamic–pituitary–adrenal (HPA) axis. The medial septum cholinergic neurons extensively innervate the hippocampus. Although, the cholinergic septohippocampal pathway (SHP) has long been implicated in learning and memory, its involvement in mediating the adaptive and maladaptive impact of stress on mnemonic processes remains less clear. Here, we discuss current research highlighting the contributions of cholinergic SHP in modulating memory encoding, consolidation and retrieval. Then, we present evidence supporting the view that neurobiological interactions between HPA axis stress response and cholinergic signalling impact hippocampal computations. Finally, we critically discuss potential challenges and opportunities to target cholinergic SHP as a therapeutic strategy to improve cognitive impairments in stress‐related disorders. We argue that such efforts should consider recent conceptualisations on the dynamic nature of cholinergic signalling in modulating distinct subcomponents of memory and its interactions with cellular substrates that regulate the adaptive stress response. [ABSTRACT FROM AUTHOR]

Alveologenesis is the final stage of lung development in which the internal surface area of the lung is increased to facilitate efficient gas exchange in the mature organism. The first phase of alveologenesis involves the formation of septal ridges (secondary septae) and the second phase involves thinning of the alveolar septa. Within secondary septa, mesenchymal cells include a transient population of alveolar myofibroblasts (MyoFBs) and a stable but poorly described population of lipid-rich cells that have been referred to as lipofibroblasts or matrix fibroblasts (MatFBs). Using a unique Fgf18CreER lineage trace mouse line, cell sorting, single-cell RNA sequencing and primary cell culture, we have identified multiple subtypes of mesenchymal cells in the neonatal lung, including an immature progenitor cell that gives rise to mature MyoFB. We also show that the endogenous and targeted ROSA26 locus serves as a sensitive reporter for MyoFB maturation. These studies identify a MyoFB differentiation program that is distinct from other mesenchymal cell types and increases the known repertoire of mesenchymal cell types in the neonatal lung. [ABSTRACT FROM AUTHOR]

Background: Bundle branch reentrant ventricular tachycardia is a unique type of VT that employs both bundles and the ventricular septum as integral components of a re-entrant circuit. It is usually observed in dilated cardiomyopathy, and its circuit depends exclusively on the specialized conduction system. Case presentation: A 67-year-old man with a history of Fabry disease, and atrial fibrillation ablation, was admitted for a wide QRS tachycardia at 150 bpm, with an LBBB. Pharmacological therapy failed to stop the arrhythmia. Intracardiac recordings confirm the diagnosis. His Bundle recordings are essential, and Atrioventricular (AV) dissociation is typically present. The method used to induce left BBRVT is right ventricle apex stimulation. An electrophysiological study showed an AV dissociation a long HV sequence and a similar QRS morphology between VT and sinus rhythm. An overdrive stopped it. The same arrhythmia reappears and is restored to sinus rhythm by electrical cardioversion. We decided to implant an Implantable Cardiac defibrillator (ICD) with a backup pacing for secondary prevention and to ablate the right bundle branch. Conclusion: BBRVT is a rare entity that is underreported. Pharmacological therapy is usually inefficient. An ICD is recommended for secondary prevention and can provide backup pacing, frequently required after catheter ablation to prevent the development of AV block or an excessive prolonged HV interval. Catheter ablation of the bundle branch is the first-line therapy. [ABSTRACT FROM AUTHOR]

Responding to social signals by expressing the correct behavior is not only challenged in autism but also in diseases with a high prevalence of autism, such as Prader-Willi syndrome. Clinical evidence suggests that aberrant prosocial behavior in patients can be regulated by intranasal oxytocin (OXT) or vasopressin (AVP). However, the neuronal mechanisms that underlie impaired behavioral responses in a socially aversive context, and how can they be corrected, remain largely unknown. Using the Magel2 knockout mouse model of Prader-Willi syndrome (crossed with CRE-dependent transgenic lines), we devised optogenetic, physiological, and pharmacological strategies in a social fear conditioning paradigm. Pathway-specific roles of OXT and AVP signaling were investigated converging on the lateral septum (LS), a region that receives dense hypothalamic inputs. OXT and AVP signaling promoted inhibitory synaptic transmission in the LS, the failure of which in Magel2 knockout mice disinhibited somatostatin (SST) neurons and disrupted social fear extinction. The source of OXT and AVP deficits mapped specifically in the supraoptic nucleus→LS pathway of Magel2 knockout mice with disrupted social fear extinction, which could be corrected by optogenetic or pharmacological inhibition of SST neurons in the LS. Interestingly, LS SST neurons also gated the expression of aggressive behavior, possibly as part of functional units that operate beyond local septal circuits. SST cells in the LS play a crucial role in integration and expression of disrupted neuropeptide signals in autism, thereby altering the balance in expression of safety versus fear. Our results uncover novel mechanisms underlying dysfunction in a socially aversive context and provide a new framework for future treatments for autism spectrum disorder. [ABSTRACT FROM AUTHOR]

Emotional disorders, such as anxiety and depression, represent a major societal problem; however, the underlying neurological mechanism remains unknown. The ventral lateral septum (LSv) is implicated in regulating processes related to mood and motivation. In this study, we found that LSv GABAergic neurons were significantly activated in mice experiencing chronic social defeat stress (CSDS) after exposure to a social stressor. We then controlled LSv GABAergic neuron activity using a chemogenetic approach. The results showed that although manipulation of LSv GABAergic neurons had little effect on anxietylike behavioral performances, the activation of LSv GABAergic neurons during CSDS worsened social anxiety during a social interaction (SI) test. Moreover, LSv GABAergic neurons showed strong projections to the paraventricular nucleus (PVN) of the hypothalamus, which is a central hub for stress reactions. Remarkably, while activation of GABAergic LSv-PVN projections induced social anxiety under basal conditions, activation of this pathway during CSDS alleviated social anxiety during the SI test. On the other hand, the chemogenetic manipulation of LSv GABAergic neurons or LSvGABA-PVN projections had no significant effect on despair-like behavioral performance in the tail suspension test. Overall, LS GABAergic neurons, particularly the LSv GABAergic-PVN circuit, has a regulatory role in pathological anxiety and is thus a potential therapeutic target for the treatment of emotional disorders. [ABSTRACT FROM AUTHOR]

Basal forebrain cholinergic dysfunction, most likely linked with tau protein aggregation, is a characteristic feature of Alzheimer's disease (AD). Recent evidence suggests that tau protein is a putative target for the treatment of dementia, and the tau aggregation inhibitor, hydromethylthionine mesylate (HMTM), has emerged as a potential disease-modifying treatment. However, its efficacy was diminished in patients already receiving approved acetylcholinesterase inhibitors. In this study, we ask whether this negative interaction can also be mimicked in experimental tau models of AD and whether the underlying mechanism can be understood. From a previous age profiling study, 6-month-old line 1 (L1) tau transgenic mice were characterized by a severe reduction in several cholinergic markers. We therefore assessed whether long-term pre-exposure with the acetylcholinesterase inhibitor rivastigmine alone and in conjunction with the tau aggregation inhibitor HMTM can reverse cholinergic deficits in L1. Rivastigmine and HMTM, and combinations of the two compounds were administered orally for 11 weeks to both L1 and wild-type mice. The brains were sectioned with a focus on the basal forebrain, motor cortex and hippocampus. Immunohistochemical staining and quantification of choline acetyltransferase (ChAT), tyrosine kinase A (TrkA)-positive neurons and relative optical intensity (ROI) for vesicular acetylcholine transporter (VAChT), and acetylcholinesterase (AChE) reactivity confirmed reversal of the diminished cholinergic phenotype of interneurons (nucleus accumbens, striatum) and projection neurons (medial septum, nucleus basalis magnocellularis) by HMTM, to a greater extent than by rivastigmine alone in L1 mice. Combined administration did not yield additivity but, in most proxies, led to antagonistic effects in which rivastigmine decreased the benefits shown with HMTM alone. Local markers (VAChT and AChE) in target structures of the basal forebrain, motor cortex and hippocampal CA3 seemed to be normalized by HMTM, but not by rivastigmine or the combination of both drugs. HMTM, which was developed as a tau aggregation inhibitor, strongly decreased the tau load in L1 mice, however, not in combination with rivastigmine. Taken together, these data confirm a cholinergic phenotype in L1 tau transgenic mice that resembles the deficits observed in AD patients. This phenotype is reversible by HMTM, but at the same time appears to be subject to a homeostatic regulation induced by chronic pre-treatment with an acetylcholinesterase inhibitor, which interferes with the efficacy of HMTM. The strongest phenotypic reversal coincided with a normalization of the tau load in the cortex and hippocampus of L1, suggesting that tau accumulation underpins the loss of cholinergic markers in the basal forebrain and its projection targets. [ABSTRACT FROM AUTHOR]

The study of the maxillary sinus anatomy should consider the presence of two features of clinical importance. The arterial supply course and the presence of the so-called Underwood septa are two important factors to consider when planning surgical treatment to reduce the risk of surgical complications such as excessive bleeding and Schneiderian membrane perforations. This study aimed to investigate the above-mentioned anatomical structures to improve the management of eventual vascular and surgical complications in this area. This study included a total of 200 cone-beam computed topographies (CBCTs) divided into two groups of 100 CBCTs to evaluate the arterial supply (AAa) course through the lateral sinus wall and Underwood's septa, respectively. The main parameters considered on 3D imaging were the presence of the AAa in the antral wall, the length of the arterial pathway, the height of the maxillary bone crest, the branch sizes of the artery in the first group, and the position of the septa, the length of the septa, and their gender associations in the second group. The CBCT analysis showed the presence of the arterial supply through the bone wall in 100% of the examined patients, with an average size of 1.07 mm. With regard to the septa, 19% of patients presented variations, and no gender difference was found to be statistically significant. The findings add to the current understanding of the clinical structure of the maxillary sinus, equipping medical professionals with vital details for surgical preparation and prevention of possible complications. [ABSTRACT FROM AUTHOR]

After a nasoseptal flap (NSF) is performed for skull base reconstruction, patients often have significant crusting along the exposed anterior cartilaginous septum and delayed remucosalization. Placing a free mucosal graft (FMG) on the NSF donor site cartilage can help improve postoperative sinonasal symptoms. In this video, we demonstrate the use of a septal stapler to secure a septal FMG to the NSF donor site following endoscopic endonasal resection of a pituitary adenoma.By Jessa E. Miller; Jakob L. Fischer and Marilene B. WangReported by Author; Author; Author [Extracted from the article]

Introduction: Periodontitis is a prevalent and severe dental condition characterized by the gradual degradation of the bone surrounding the teeth. Over the past two decades, numerous epidemiological investigations have suggested a potential link between periodontitis and cardiovascular disease. However, the complex mechanistic relationship between oral health issues and cardiovascular disorders remains unclear. Aim: This study aimed to explore comprehensively the cardiac function through various methods, including conventional echocardiography, intraventricular pressure gradient (IVPG) analysis, speckle tracking echocardiography (STE), and hemodynamics analysis. Methods: Ligature-induced periodontitis was established in a group of rats while the second group served as sham. The successful establishment of the periodontitis model was confirmed through staining and radiographic examination of the affected mandibles. Results: X-ray films and methylene blue staining revealed alveolar bone resorption in the affected first molar in the model rats, confirming the successful induction of periodontitis. The rats with periodontitis displayed a decrease in ejection fraction compared to the sham group, accompanied by a decrease in mid-to-apical IVPG and mid IVPG. Lower values of strain rate were recorded in the apical segment of the septum, the middle segment of the septum, and the basal segment of the lateral free wall in the periodontitis group, which was associated with histopathological examination showing some degree of myocardial tissue damage. Conversely, rats with periodontitis showed an increase in heart rate, end-systolic volume, and arterial elastance when compared to the sham rats. However, they also exhibited a decrease in stroke work, stroke volume, cardiac output, and end-systolic pressure. Conclusion: This study suggests that experimental periodontitis may lead to cardiac dysfunction especially compromised systolic function and myocardial relaxation, potentially indicating an increased risk of cardiovascular events in clinical periodontitis cases. The comprehensive assessment of cardiac function, hemodynamics, and histopathological evaluation underscores the profound impact of periodontitis on heart functions within this specific experimental model. [ABSTRACT FROM AUTHOR]

Objectives: We investigated the relationship between anemia and cardiac functions by conventional and speckle-tracking echocardiography (STE) in patients with end-stage renal disease (ESRD) receiving hemodialysis. Methods: One hundred and six patients with ESRD receiving hemodialysis were included in this cross-sectional study. The conventional echocardiography and STE findings were compared between the patients with and without anemia. In addition, a comparison of the findings between the ESRD patients and healthy controls consisting of 68 participants was conducted. Results: Compared to healthy controls, ESRD patients had lower left ventricular ejection fraction (LVEF), left ventricular global longitudinal strain (LVGLS), and left atrial reservoir strain (LASr) [53% (48-57) vs. 65% (62-68), -15.2 (-16.9˗ -13.6) vs. -19.7 (-16.9˗ -13.6), and -21.9 (-29.5˗ -15.3) vs. -29.9 (-35.3˗ -22.8), respectively, P-value <0.001 for all]. Of the ESRD patients, 70 (66%) had anemia. ESRD patients with anemia had higher interventricular septum (IVS), posterior wall (PW), and left atrial volume index (LAVi) values than patients without anemia. In addition, ESRD patients with anemia had lower LVEF, LVGLS, and LASr than patients without anemia [median (IQR), 13 (12-15) vs. 12 (11-14), P=0.004, 13 (12-15) vs. 12 (11-13.5), P<0.005, 43 (35-55) vs. 34.7 (28-50), P=0.013, 52 (48-55) vs. 56 (47.5-60), P=0.016, -14.6 (-16.4˗ -13.5) vs. -16 (-18.6˗ -14.7), P=0.003, and -21.6 (-30.5˗ -16.3) vs. -30.5 (-33.6˗ -23.3), P=0.006, respectively]. In multivariable logistic regression analysis, diabetes, PW, LASr, and LVGLS were independently associated with the presence of anemia in ESRD patients. Conclusion: Our study confirmed impaired cardiac mechanics in ESRD hemodialysis patients and showed that anemia was associated with further worsening cardiac mechanics in this population. [ABSTRACT FROM AUTHOR]

Introduction: Neural exaptations represent descent via transitions to novel neural functions. A primary transition in human cognitive and neural evolution was from a predominantly socially oriented primate brain to a brain that also instantiates and subserves science, technology, and engineering, all of which depend on mathematics. Upon what neural substrates and upon what evolved cognitive mechanisms did human capacities for science, technology, engineering, and mathematics (STEM), and especially its mathematical underpinnings, emerge? Previous theory focuses on roles for tools, language, and arithmetic in the cognitive origins of STEM, but none of these factors appears sufficient to support the transition. Methods: In this article, I describe and evaluate a novel hypothesis for the neural origins and substrates of STEM-based cognition: that they are based in human kinship systems and human maximizing of inclusive fitness. Results: The main evidence for this hypothesis is threefold. First, as demonstrated by anthropologists, human kinship systems exhibit complex mathematical and geometrical structures that function under sets of explicit rules, and such systems and rules pervade and organize all human cultures. Second, human kinship underlies the core algebraic mechanism of evolution, maximization of inclusive fitness, quantified as personal reproduction plus the sum of all effects on reproduction of others, each multiplied by their coefficient of relatedness to self. This is the only "natural" equation expected to be represented in the human brain. Third, functional imaging studies show that kinship-related cognition activates frontal-parietal regions that are also activated in STEM-related tasks. In turn, the decision-making that integrates kinship levels with costs and benefits from alternative behaviors has recently been shown to recruit the lateral septum, a hub region that combines internal (from the prefrontal cortex, amygdala, and other regions) and external information relevant to social behavior, using a dedicated subsystem of neurons specific to kinship. Conclusions: Taken together, these lines of evidence suggest that kinship systems and kin-associated behaviors may represent exaptations for the origin of human STEM. [ABSTRACT FROM AUTHOR]

The hypothalamic supramammillary nucleus (SuM) plays a crucial role in controlling wakefulness, but the downstream target regions participating in this control process remain unknown. Here, using circuit-specific fiber photometry and single-neuron electrophysiology together with electroencephalogram, electromyogram and behavioral recordings, we find that approximately half of SuM neurons that project to the medial septum (MS) are wake-active. Optogenetic stimulation of axonal terminals of SuM-MS projection induces a rapid and reliable transition to wakefulness from non-rapid-eye movement or rapid-eye movement sleep, and chemogenetic activation of SuMMS projecting neurons significantly increases wakefulness time and prolongs latency to sleep. Consistently, chemogenetically inhibiting these neurons significantly reduces wakefulness time and latency to sleep. Therefore, these results identify the MS as a functional downstream target of SuM and provide evidence for the modulation of wakefulness by this hypothalamic-septal projection. In vivo recordings show that a subset of supramammillary neurons that project to the medial septum are wake-active, and projection-specific manipulations reveal that this hypothalamic-septal projection contributes to wakefulness modulation. [ABSTRACT FROM AUTHOR]

In complex social environments, individuals may interact with not only novel and familiar conspecifics but also kin and non-kin. The ability to distinguish between conspecific identities is crucial for most animals, yet how the brain processes conspecific type and how animals may alter behavior accordingly is not well known. We examined whether the communally breeding spiny mouse (Acomys cahirinus) responds differently to conspecifics that vary in novelty and kinship. In a group interaction test, we found that males can distinguish novel kin from novel non-kin, and preferentially spend time with novel kin over familiar kin and novel non-kin. To determine whether kinship and novelty status are differentially represented in the brain, we conducted immediate early gene tests, which revealed the dorsal, but not ventral, lateral septum differentially processes kinship. Neither region differentially processes social novelty. Further, males did not exhibit differences in prosocial behavior toward novel and familiar conspecifics but exhibited more prosocial behavior with novel kin than novel non-kin. These results suggest that communally breeding species may have evolved specialized neural circuitry to facilitate a bias to be more affiliative with kin, regardless of whether they are novel or familiar, potentially to promote prosocial behaviors, thereby facilitating group cohesion. [ABSTRACT FROM AUTHOR]

The cartilaginous nasal septum is integral to the overall structure of the nose. Developing our an-atomic understanding of the septum will improve the planning and techniques of septal surgeries. While the basic dimensions of the septum have previously been described, the average shape in the sagittal plane has yet to be established. Furthermore, determining the average shape allows for the creation of a mean three-dimensional (3D) septum model. To better understand the average septal shape, we dissected septums from 40 fresh human cadavers. Thickness was measured across pre-defined points on each specimen. Image processing in Photoshop was used to superimpose lateral photographs of the septums to determine the average shape. The average shape was then combined with thickness data to develop a 3D model. This model may be utilized in finite elemental analyses, creating theoretical results about septal properties that are more translatable to real-world clinical practice. Our 3D septum also has numerous applications for 3D printing. Realistic models can be created for educational or surgical planning purposes. In the future, our model could also serve as the basis for 3D-printed scaffolds to aid in tissue regeneration to reconstruct septal defects. The model can be viewed at the NIH 3D model repository (3DPX ID: 020598, Title: 3D Nasal Septum). [ABSTRACT FROM AUTHOR]

Women are at a higher risk of cognitive impairments and Alzheimer's disease (AD), particularly after the menopause, when the estrous cycle becomes irregular and diminishes. Numerous studies have shown that estrogen deficiency, especially estradiol (E2) deficiency, plays a key role in this phenomenon. Recently, a novel polymeric drug, hyaluronic acid–17β-estradiol conjugate (HA-E2), has been introduced for the delivery of E2 to brain tissues. Studies have indicated that HA-E2 crosses the blood–brain barrier (BBB) and facilitates a prolonged E2 release profile while lowering the risk of estrogen-supplement-related side effects. In this study, we used ovariohysterectomy (OHE) rats, a postmenopausal cognitive deficit model, to explore the effect of a 2-week HA-E2 treatment (210 ng/kg body weight, twice a week) on the cholinergic septo-hippocampal innervation system, synaptic transmission in hippocampal pyramidal neurons and cognitive improvements. Our study revealed an 11% rise in choline acetyltransferase (ChAT) expression in both the medial septal nucleus (MS nucleus) and the hippocampus, along with a 14–18% increase in dendritic spine density in hippocampal pyramidal neurons, following HA-E2 treatment in OHE rats. These enhancements prompted the recovery of cognitive functions such as spatial learning and memory. These findings suggest that HA-E2 may prevent and improve estrogen-deficiency-induced cognitive impairment and AD. [ABSTRACT FROM AUTHOR]

Primary and secondary septa formed during lung development contain a double-layered capillary network. To improve gas exchange, the capillary network is remodeled into a single-layered one, a process that is called microvascular maturation (MVM). It takes place during classical and continued alveolarization. Classical alveolarization is defined as a formation of new septa from immature septa and continued alveolarization as a formation from mature septa. Until now, MVM was never quantitatively evaluated in human lungs. To correlate alveolarization and MVM, and to determine the transition point from classical to continued alveolarization, the degree of MVM was stereologically estimated. In 12 human lungs (0.1-15 yr), the alveolar surface area of immature and mature septa was estimated stereologically by intersection counting. An MVM-quotient (RMVM) was defined as the mature alveolar surface area over total alveolar surface area. The MVM-quotient increased logarithmically over age and showed a biphasic increase similar to alveolarization. It did not reach 100% maturity in these samples. A linear correlation between the MVM-quotient and the logarithm of the number of alveoli was observed. We conclude that MVM increased logarithmically and biphasically in parallel to alveolarization until alveolarization ceased. However, at 2-3 yr of age three-quarters of the alveolar microvasculature are mature. This result may explain a previous postulate that MVM is finished at this age. We hypothesize that as long as alveolarization takes place, MVM will take place in parallel. We propose that the transition from classical to continued alveolarization takes place between the ages of 1-3 yr in humans. NEW & NOTEWORTHY Newly formed alveolar septa contain a double-layered capillary network. To optimize gas exchange, the two layers fuse to a single-layered capillary network during microvascular maturation. Because its timing is unknow in humans, microvascular maturation was stereologically estimated throughout postnatal human lung development. It is shown that maturation of the microvascular and alveolar septa takes place in parallel to alveolarization. At an age of 2-3 yr three-quarters of the septa are mature. [ABSTRACT FROM AUTHOR]

Hippocampal theta oscillations orchestrate faster beta-to-gamma oscillations facilitating the segmentation of neural representations during navigation and episodic memory. Supra-theta rhythms of hippocampal CA1 are coordinated by local interactions as well as inputs from the entorhinal cortex (EC) and CA3 inputs. However, theta-nested gamma-band activity in the medial septum (MS) suggests that the MS may control supra-theta CA1 oscillations. To address this, we performed multi-electrode recordings of MS and CA1 activity in rodents and found that MS neuron firing showed strong phase-coupling to theta-nested supra-theta episodes and predicted changes in CA1 beta-to-gamma oscillations on a cycle-by-cycle basis. Unique coupling patterns of anatomically defined MS cell types suggested that indirect MS-to-CA1 pathways via the EC and CA3 mediate distinct CA1 gamma-band oscillations. Optogenetic activation of MS parvalbumin-expressing neurons elicited theta-nested beta-to-gamma oscillations in CA1. Thus, the MS orchestrates hippocampal network activity at multiple temporal scales to mediate memory encoding and retrieval. Timing is key for efficient coding and communication across brain areas. Here, the authors found that the medial septum orchestrates hippocampal network activity at multiple temporal scales likely mediating memory encoding and retrieval. [ABSTRACT FROM AUTHOR]

Dystrophic neurites (DNs) are abnormal axons and dendrites that are swollen or deformed in various neuropathological conditions. In Alzheimer's disease (AD), DNs play a crucial role in impairing neuronal communication and function, and they may also contribute to the accumulation and spread of amyloid beta (Aβ) in the brain of AD patients. However, it is still a challenge to understand the DNs of specific neurons that are vulnerable to Aβ in the pathogenesis of AD. To shed light on the development of radiating DNs, we examined enriched dystrophic hippocampal axons in a mouse model of AD using a three-dimensional rendering of projecting neurons. We employed the anterograde spread of adeno-associated virus (AAV)1 and conducted proteomic analysis of synaptic compartments obtained from hippocampo-septal regions. Our findings revealed that DNs were formed due to synaptic loss at the axon terminals caused by the accumulation of extracellular vesicle (EV). Abnormal EV-mediated transport and exocytosis were identified in association with primary cilia, indicating their involvement in the accumulation of EVs at presynaptic terminals. To further address the regulation of DNs by primary cilia, we conducted knockdown of the Ift88 gene in hippocampal neurons, which impaired EV-mediated secretion of Aβ and promoted accumulation of axonal spheroids. Using single-cell RNA sequencing, we identified the septal projecting hippocampal somatostatin neurons (SOM) as selectively vulnerable to Aβ with primary cilia dysfunction and vesicle accumulation. Our study suggests that DNs in AD are initiated by the ectopic accumulation of EVs at the neuronal axon terminals, which is affected by neuronal primary cilia. [ABSTRACT FROM AUTHOR]

The left and right hippocampal formation (HF) of the avian brain have been reported to control some different aspects of homing in pigeons. In the current study, we employed GPS-tracking technology and unilateral HF lesions to further explore what if any aspects of a pigeon's homing flight might be under dominant control by either the left or right HF. Pigeons were released from three locations prior to any experimental manipulation and released repeatedly from the same three sites as sham-lesioned control, right HF-lesioned and left HF-lesioned treatment groups. Analyses of homing performance and virtual vanishing bearings revealed no effect of either lesion treatment. A more in-depth analysis of path efficiency during the initial decision-making, en route and near home phases of a homing flight also revealed no effect of either lesion treatment. A last analysis on the learning and memory for positions along a previously flown route, a proxy for investigating the development of route fidelity, also revealed no effect of either unilateral lesion. However, independent of treatment group, some statistically significant effects were observed with respect to changes in performance across training and the different release sites. The current study revealed no detectable difference between the left and right HF-lesioned pigeons with respect to several navigational parameters of a homing flight. Although in need of supporting experimentation, the results are consistent with the hypothesis that both the left and right HF are similarly able to support several aspects of homing pigeon navigation. No effect of unilateral HF-lesions on pigeons' homing was found. Both the left and right HF support local navigation and route fidelity development. [ABSTRACT FROM AUTHOR]

Given the unique expression patterns and revelations of its critical involvement in a host of neurological disorders, the TRPC1/4/5 subgroup has become an intense target of drug development, and some compounds are now in clinical trials. However, little is known about the exact subunit composition of this subfamily of TRPC channels in various native tissues, and whether it has functional and pharmacological implications. In this study, we investigated the effects of two TRPC4 modulators located in the lateral septum, in which a metabotropic glutamate receptor (mGluR) agonist-induced plateau potential is mediated by TRPC channels composed of TRPC1 and TRPC4. Lateral septal neurons were recorded intracellularly in brain slices using sharp electrodes. Drugs were applied via bath superfusion. We showed that the plateau potential in mice lacking TRPC1 is modulated by ML204 and La3+ in a manner that is like homomeric TRPC4 channels in artificial expression systems. However, the plateau potential that is primarily mediated by heteromeric TRPC1/4 channels in lateral septal neurons in wildtype mice was modulated differently by ML204 and La3+. Our data suggest that native homomeric TRPC4 channels and heteromeric TRPC1/4 channels are pharmacologically distinct, and the current drug development strategy regarding TRPC1/4/5 may need to be reevaluated. [ABSTRACT FROM AUTHOR]

Background and aims: The onion (Allium cepa var. cepa) is an allogamous species in which male-sterile lines have been developed. However, the structure of the flower and floral nectaries have only been briefly described. The objective of this study is to update the floral anatomy data, comparing the gynoecium and androecium of male-fertile and male-sterile lines, and to analyze the three-dimensional structure of the floral nectary. M&M: Conventional optical and scanning electron microscopy techniques were used. Results: Fertile and sterile male flowers have the same structural organization. The septal or gynopleural nectary is organized in three zones: 1) production area formed by the glandular tissue arranged radially in the septa of the ovary, 2) discharge zone: a small channel at the apex connects the nectariferous tissue with the pocket formed between the ovary wall and the overlying ridge, and 3) presentation and harvest zone, where the excreted nectar accumulates, formed between the widened base of the inner staminal filaments opposite the ovary. Conclusions: The only anatomical differences in the flowers sterile male lines are the lack of pollen production and the absence of dehiscence, despite having a normal stomium and anther wall. The floral nectaries of onion are a clear example of secondary presentation of nectar. [ABSTRACT FROM AUTHOR]

Single-cell transcriptomics are powerful tools to define neuronal cell types based on co-expressed gene clusters. Limited RNA input in these technologies necessarily compromises transcriptome coverage and accuracy of differential expression analysis. We propose that bulk RNA-Seq of neuronal pools defined by spatial position offers an alternative strategy to overcome these technical limitations. We report a laser-capture microdissection (LCM)-Seq method which allows deep transcriptome profiling of fluorescently tagged neuron populations isolated with LCM from histological sections of transgenic mice. Mild formaldehyde fixation of ZsGreen marker protein, LCM sampling of ~300 pooled neurons, followed by RNA isolation, library preparation and RNA-Seq with methods optimized for nanogram amounts of moderately degraded RNA enabled us to detect ~15,000 different transcripts in fluorescently labeled cholinergic neuron populations. The LCM-Seq approach showed excellent accuracy in quantitative studies, allowing us to detect 2891 transcripts expressed differentially between the spatially defined and clinically relevant cholinergic neuron populations of the dorsal caudateputamen and medial septum. In summary, the LCM-Seq method we report in this study is a versatile, sensitive, and accurate bulk sequencing approach to study the transcriptome profile and differential gene expression of fluorescently tagged neuronal populations isolated from transgenic mice with high spatial precision. [ABSTRACT FROM AUTHOR]

The fighting fish Betta splendens, long studied for its aggressive territorial competitions, has the potential to be a tractable and relevant model for studying the intersection of cognitive ecology and social neuroscience. Yet, few studies have comprehensively assessed Betta behavior across both social and nonsocial contexts. Furthermore, the present study is the first to quantify the expression of phosphorylated ribosomal protein S6 (PS6), a proxy for neural response, in the Betta telencephalon. Here, we assessed male Betta behavior across a suite of tasks and found that response to a mirror, but not neophilia (a novel object) nor anxiety (scototaxis), predicted behavior in a social competition. To then explore the cognitive aspects of social competition, we exposed Betta to either a familiar or novel opponent and compared their competitive behavior as well as their neural responses in the teleost homologs of the hippocampus, basolateral amygdala, and lateral septum. We did not detect any differences between familiar-exposed and novel-exposed individuals, but by implementing the first use of a habituation–dishabituation competition design in a study of Betta, we were able to observe remarkable consistency in competitive outcomes across repeated exposures. Taken together, the present study lays the groundwork for expanding the use of Betta to explore integrative and multidimensional questions of social cognition. [ABSTRACT FROM AUTHOR]

Aim: Partial anomalous pulmonary venous connection (PAPVC) is a rare congenital cardiovascular anomaly characterized by one or more, but not all, pulmonary veins draining into the right atrium. This condition can occur in isolation or in conjunction with other cardiac abnormalities such as an atrial septal defect (ASD). In this study we aimed to investigate the clinical presentation, diagnostic approaches, management options, and outcomes of patients with PAPVC. Materials and Methods: This retrospective study included 140 patients diagnosed with isolated or ASD-associated PAPVC between January 2010 and December 2022. Results: The median age at presentation was 5 years (1 month to 39 years). Isolated PAPVC was observed in 36 patients (25.7%), while 104 patients (74.3%) had an atrial septal defect (ASD). In our patient cohort, 119 patients (85%) exhibited partially affected anomalous PVs, while the remaining 21 patients (15%) presented with anomalous pulmonary veins involving the entire lung. Right-sided PVs were involved in 116 patients (82.8%), left-sided PVs in 20 patients (14.3%), and both right and left PVs in 4 patients (2.9%). Malposition of primum septum was detected in 8 patients (5.8%), and scimitar syndrome was present in 7 patients (5%). Surgical treatment was performed in 71.4% (n=100) of the patients, while catheter angiography with vertical vein occlusion was performed in 2 patients with dual drainage. Conclusion: Despite the infrequency and complexity of PAPVC, timely identification and customized surgical intervention can help avert serious complications. The application of advanced imaging technologies in diagnosis and surgical planning is crucial. [ABSTRACT FROM AUTHOR]

Aim: This study mapped the spatiotemporal positions and connectivity of Onecut3+ neuronal populations in the developing and adult mouse brain. Methods: We generated fluorescent reporter mice to chart Onecut3+ neurons for brain‐wide analysis. Moreover, we crossed Onecut3‐iCre and Mapt‐mGFP (Tau‐mGFP) mice to visualize axonal projections. A dual Cre/Flp‐dependent AAV construct in Onecut3‐iCre cross‐bred with Slc17a6‐FLPo mice was used in an intersectional strategy to map the connectivity of glutamatergic lateral hypothalamic neurons in the adult mouse. Results: We first found that Onecut3 marks a hitherto undescribed Slc17a6+/Vglut2+ neuronal cohort in the lateral hypothalamus, with the majority expressing thyrotropin‐releasing hormone. In the adult, Onecut3+/Vglut2+ neurons of the lateral hypothalamus had both intra‐ and extrahypothalamic efferents, particularly to the septal complex and habenula, where they targeted other cohorts of Onecut3+ neurons and additionally to the neocortex and hippocampus. This arrangement suggests that intrinsic reinforcement loops could exist for Onecut3+ neurons to coordinate their activity along the brain's midline axis. Conclusion: We present both a toolbox to manipulate novel subtypes of hypothalamic neurons and an anatomical arrangement by which extrahypothalamic targets can be simultaneously entrained. [ABSTRACT FROM AUTHOR]

It was the aim of this prospective cohort study to assess the various anatomical and other patient-related factors that increase membrane perforation risk. Patients underwent cone-beam computed tomography (CBCT) before surgery. The presence of septa, presence of mucous retention cyst, lateral wall thickness, membrane thickness, and residual bone height were predictive factors. Age, gender, and smoking were covariates for the study. The presence or absence of membrane perforation was the study outcome. In total, 140 subjects were studied. The hazard ratio (HR) for the presence of septa with membrane perforation was 8.07 (2.93–22.29) (p < 0.001). The HR for perforation with a single edentulous area relating to two or more teeth was 68.09 (9.52–49.16). The risk of membrane perforation in smokers was 25 times more than in non-smokers — HR 25 (7.58–82.51) (p < 0.001). The HR for membrane perforation in subjects with mucous retention cysts compared with subjects without retention cysts was 27.75 (8.73–88.23) (p < 0.001). Within the limitations of the study it seems that anatomical, habitual, and pathological factors may increase the risk of Schneiderian membrane perforation when a lateral window approach is used for sinus floor augmentation. [ABSTRACT FROM AUTHOR]

Post-operative sleep disturbance is a common feature of elderly surgical patients, and sleep fragmentation (SF) is closely related to post-operative cognitive dysfunction (POCD). SF is characterized by sleep interruption, increased number of awakenings and sleep structure destruction, similar to obstructive sleep apnea (OSA). Research shows that sleep interruption can change neurotransmitter metabolism and structural connectivity in sleep and cognitive brain regions, of which the medial septum and hippocampal CA1 are key brain regions connecting sleep and cognitive processes. Proton magnetic resonance spectroscopy (1H-MRS) is a non-invasive method for the evaluation of neurometabolic abnormalities. Diffusion tensor imaging (DTI) realizes the observation of structural integrity and connectivity of brain regions of interest in vivo. However, it is unclear whether post-operative SF induces harmful changes in neurotransmitters and structures of the key brain regions and their contribution to POCD. In this study, we evaluated the effects of post-operative SF on neurotransmitter metabolism and structural integrity of medial septum and hippocampal CA1 in aged C57BL/6J male mice. The animals received a 24-h SF procedure after isoflurane anesthesia and right carotid artery exposure surgery. 1H-MRS results showed after postoperative SF, the glutamate (Glu)/creatine (Cr) and glutamate + glutamine (Glx)/Cr ratios increased in the medial septum and hippocampal CA1, while the NAA/Cr ratio decreased in the hippocampal CA1. DTI results showed post-operative SF decreased the fractional anisotropy (FA) of white matter fibers in the hippocampal CA1, while the medial septum was not affected. Moreover, post-operative SF aggravated subsequent Y-maze and novel object recognition performances accompanied by abnormal enhancement of glutamatergic metabolism signal. This study suggests that 24-h SF induces hyperglutamate metabolism level and microstructural connectivity damage in sleep and cognitive brain regions in aged mice, which may be involved in the pathophysiological process of POCD. [ABSTRACT FROM AUTHOR]

Polycystic ovary syndrome (PCOS) is a female endocrine disorder that is associated with prenatal exposure to excess androgens. In prenatally androgenized (PNA) mice that model PCOS, GABAergic neural transmission to and innervation of GnRH neurons is increased. Evidence suggests that elevated GABAergic innervation originates in the arcuate nucleus (ARC). We hypothesized that GABA‐GnRH circuit abnormalities are a direct consequence of PNA, resulting from DHT binding to androgen receptor (AR) in the prenatal brain. However, whether prenatal ARC neurons express AR at the time of PNA treatment is presently unknown. We used RNAScope in situ hybridization to localize AR mRNA (Ar)‐expressing cells in healthy gestational day (GD) 17.5 female mouse brains and to assess coexpression levels in specific neuronal phenotypes. Our study revealed that less than 10% of ARC GABA cells expressed Ar. In contrast, we found that ARC kisspeptin neurons, critical regulators of GnRH neurons, were highly colocalized with Ar. Approximately 75% of ARC Kiss1‐expressing cells also expressed Ar at GD17.5, suggesting that ARC kisspeptin neurons are potential targets of PNA. Investigating other neuronal populations in the ARC we found that ~50% of pro‐opiomelanocortin (Pomc) cells, 22% of tyrosine hydroxylase (Th) cells, 8% of agouti‐related protein (Agrp) cells and 8% of somatostatin (Sst) cells express Ar. Lastly, RNAscope in coronal sections showed Ar expression in the medial preoptic area (mPOA), and the ventral part of the lateral septum (vLS). These Ar‐expressing regions were highly GABAergic, and 22% of GABA cells in the mPOA and 25% of GABA cells in the vLS also expressed Ar. Our findings identify specific neuronal phenotypes in the ARC, mPOA, and vLS that are androgen sensitive in late gestation. PNA‐induced functional changes in these neurons may be related to the development of impaired central mechanisms associated with PCOS‐like features. [ABSTRACT FROM AUTHOR]

Background The medial prefrontal cortex (mPFC) is necessary for cognitive flexibility and projects to medial septum (MS). MS activation improves strategy switching, a common measure of cognitive flexibility, likely via its ability to regulate midbrain dopamine (DA) neuron population activity. We hypothesized that the mPFC to MS pathway (mPFC-MS) may be the mechanism by which the MS regulates strategy switching and DA neuron population activity. Methods Male and female rats learned a complex discrimination strategy across 2 different training time points: a constant length (10 days) and a variable length that coincided with each rat meeting an acquisition-level performance threshold (males: 5.3 ± 0.3 days, females: 3.8 ± 0.3 days). We then chemogenetically activated or inhibited the mPFC-MS pathway and measured each rat's ability to inhibit the prior learned discrimination strategy and switch to a prior ignored discrimination strategy (strategy switching). Results Activation of the mPFC-MS pathway improved strategy switching after 10 days of training in both sexes. Inhibition of the pathway produced a modest improvement in strategy switching that was quantitatively and qualitatively different from pathway activation. Neither activation nor inhibition of the mPFC-MS pathway affected strategy switching following the acquisition-level performance threshold training regimen. Activation, but not inhibition, of the mPFC-MS pathway bidirectionally regulated DA neuron activity in the ventral tegmental area and substantia nigra pars compacta, similar to general MS activation. Conclusions This study presents a potential top-down circuit from the prefrontal cortex to the midbrain by which DA activity can be manipulated to promote cognitive flexibility. [ABSTRACT FROM AUTHOR]

The medial septum (MS) contributes in pain processing and regulation, especially concerning persistent nociception. However, the role of MS glutamatergic neurons in pain and the underlying neural circuit mechanisms in pain remain poorly understood. In this study, chronic constrictive injury of the sciatic nerve (CCI) surgery was performed to induce thermal and mechanical hyperalgesia in mice. The chemogenetic activation of MS glutamatergic neurons decreased pain thresholds in naïve mice. In contrast, inhibition or ablation of these neurons has improved nociception thresholds in naïve mice and relieved thermal and mechanical hyperalgesia in CCI mice. Anterograde viral tracing revealed that MS glutamatergic neurons had projections to the lateral hypothalamus (LH) and supramammillary nucleus (SuM). We further demonstrated that MS glutamatergic neurons regulate pain thresholds by projecting to LH but not SuM, because the inhibition of MS-LH glutamatergic projections suppressed pain thresholds in CCI and naïve mice, yet, optogenetic activation or inhibition of MS-SuM glutamatergic projections had no effect on pain thresholds in naïve mice. In conclusion, our results reveal that MS glutamatergic neurons play a significant role in regulating pain perception and decipher that MS glutamatergic neurons modulate nociception via projections to LH. [ABSTRACT FROM AUTHOR]

Introduction: Stress may cause prospective escalations in abdominal pain magnitude and accumbal TRPV1 expression, while central neural circuits mediating these stress effects remain unclear. Methods: Using retrograde tracing methods, we first demonstrated the existence of a medial septal-dorsal lateral septal-accumbal circuit very likely involving social disruption stress-primed escalations in acid-induced writhes and accumbal TRPV1 level. An intersectional viral strategy and virus-carrying hM3Dq and hM4Di DREADDs were, then, employed to selectively modulate GABAergic and cholinergic neuronal activity in medial and dorsal lateral septum. Results: Exciting medial septal GABAergic neuron was found to prevent social disruption stress-primed escalations in acid-induced writhes and accumbal TRPV1 and PKCε expressions. Likewise, inactivating dorsal lateral septal cholinergic neurons was also effective in abolishing these stress-primed escalations. Inactivating GABAergic neuron in non-stressed animals' medial septum was found to reproduce the stress-primed effects in causing heightened acid-induced writhes and accumbal TRPV1 and PKCε levels. Discussion: These results, taken together, prompt us to conclude that social disruption stress may produce plastic changes in a newly-identified medial septal-dorsal lateral septal-accumbal circuit. Moreover, medial septal GABAergic hypoactivity and dorsal lateral septal cholinergic hyperactivity are, at least, two likely causes reflecting such stress-produced escalations in abdominal pain magnitude and pain transductionrelated protein over-expression in nucleus accumbens. [ABSTRACT FROM AUTHOR]

Hippocampal ripples are highly synchronous neural events critical for memory consolidation and retrieval. A minority of strong ripples has been shown to be of particular importance in situations of increased memory demands. The propagation dynamics of strong ripples inside the hippocampal formation are, however, still opaque. We analyzed ripple propagation within the hippocampal formation in a large open-access dataset comprising 267 Neuropixel recordings in 49 awake, head-fixed mice. Surprisingly, strong ripples (top 10% in ripple strength) propagate differentially depending on their generation point along the hippocampal longitudinal axis. The septal hippocampal pole is able to generate longer ripples that engage more neurons and elicit spiking activity for an extended time even at considerable distances. Accordingly, a substantial portion of the variance in strong ripple duration (R² = 0.463) is explained by the ripple generation location on the longitudinal axis, in agreement with a possible distinctive role of the hippocampal septal pole in conditions of high-memory demand. Moreover, we observed that the location of the ripple generation has a significant impact on the spiking rate modulation of different hippocampal subfields, even before the onset of the ripple. This finding suggests that ripple generation location plays a crucial role in shaping the neural activity across the hippocampus. [ABSTRACT FROM AUTHOR]

Major depressive disorder ranks as a major burden of disease worldwide, yet the current antidepressant medications are limited by frequent non-responsiveness and significant side effects. The lateral septum (LS) is thought to control of depression, however, the cellular and circuit substrates are largely unknown. Here, we identified a subpopulation of LS GABAergic adenosine A2A receptors (A2AR)-positive neurons mediating depressive symptoms via direct projects to the lateral habenula (LHb) and the dorsomedial hypothalamus (DMH). Activation of A2AR in the LS augmented the spiking frequency of A2AR-positive neurons leading to a decreased activation of surrounding neurons and the bi-directional manipulation of LS-A2AR activity demonstrated that LS-A2ARs are necessary and sufficient to trigger depressive phenotypes. Thus, the optogenetic modulation (stimulation or inhibition) of LS-A2AR-positive neuronal activity or LS-A2AR-positive neurons projection terminals to the LHb or DMH, phenocopied depressive behaviors. Moreover, A2AR are upregulated in the LS in two male mouse models of repeated stress-induced depression. This identification that aberrantly increased A2AR signaling in the LS is a critical upstream regulator of repeated stress-induced depressive-like behaviors provides a neurophysiological and circuit-based justification of the antidepressant potential of A2AR antagonists, prompting their clinical translation. The mechanism underlying caffeine consumption inversely correlation with depression is unclear. Here, authors identified adenosine A2A receptor in the lateral septum mediating depressive symptoms via direct outputs to the habenula and the hypothalamus. [ABSTRACT FROM AUTHOR]

The serotonin transporter (5-HTT) plays a critical role in the regulation of serotonin neurotransmission. Mice genetically deficient in 5-HTT expression have been used to study the physiological functions of 5-HTT in the brain and have been proposed as a potential animal model for neuropsychiatric and neurodevelopmental disorders. Recent studies have provided evidence for a link between the gut-brain axis and mood disorders. However, the effects of 5-HTT deficiency on gut microbiota, brain function, and behavior remain to be fully characterized. Here we investigated the effects of 5-HTT deficiency on different types of behavior, the gut microbiome, and brain c-Fos expression as a marker of neuronal activation in response to the forced swim test for assessing depression-related behavior in male 5-HTT knockout mice. Behavioral analysis using a battery of 16 different tests showed that 5-HTT−/− mice exhibited markedly reduced locomotor activity, decreased pain sensitivity, reduced motor function, increased anxiety-like and depression-related behavior, altered social behavior in novel and familiar environments, normal working memory, enhanced spatial reference memory, and impaired fear memory compared to 5-HTT+/+ mice. 5-HTT+/− mice showed slightly reduced locomotor activity and impaired social behavior compared to 5-HTT+/+ mice. Analysis of 16S rRNA gene amplicons showed that 5-HTT−/− mice had altered gut microbiota abundances, such as a decrease in Allobaculum, Bifidobacterium, Clostridium sensu stricto, and Turicibacter, compared to 5-HTT+/+ mice. This study also showed that after exposure to the forced swim test, the number of c-Fos-positive cells was higher in the paraventricular thalamus and lateral hypothalamus and was lower in the prefrontal cortical regions, nucleus accumbens shell, dorsolateral septal nucleus, hippocampal regions, and ventromedial hypothalamus in 5-HTT−/− mice than in 5-HTT+/+ mice. These phenotypes of 5-HTT−/− mice partially recapitulate clinical observations in humans with major depressive disorder. The present findings indicate that 5-HTT-deficient mice serve as a good and valid animal model to study anxiety and depression with altered gut microbial composition and abnormal neuronal activity in the brain, highlighting the importance of 5-HTT in brain function and the mechanisms underlying the regulation of anxiety and depression. [ABSTRACT FROM AUTHOR]

Acetylcholine and GABA are often co-released, including from VIP-expressing neurons of the cortex, cortically-projecting neurons of the globus pallidus externus and basal forebrain, and hippocampal-projecting neurons of the medial septum. The co-release of the functionally antagonistic neurotransmitters GABA and acetylcholine (ACh) greatly expands the possible functional effects of cholinergic neurons and provides an additional exogenous source of inhibition to the cortex. Transgene expression suggests that nearly all forebrain cholinergic neurons in mice at some point in development express Slc32a1, which encodes the vesicular GABA transporter (VGAT). To determine the degree of co-expression of GABA and Ach handling proteins, we measured expression in adult mice of Slc32a1, Gad1 and Gad2 (which encode GAD67 and GAD65, respectively, the GABA synthetic enzymes) in cholinergic neurons using fluorescent in situ hybridization. We found that only a subset of cholinergic neurons express the necessary machinery for GABA release at a single time in adult mice. This suggests that GABA co-release from cholinergic neurons is dynamic and potentially developmentally regulated. By measuring expression of Slc32a1, Gad1, Gad2, and Chat in the basal forebrain and medial septum in mice from post-natal day 0 to 28, we noted abundant yet variable expressions of GABAergic markers across early development, which are subsequently downregulated in adulthood. This is in contrast with the forebrain-projecting pedunculopontine nucleus, which showed no evidence of co-expression of GABAergic genes. These results suggest that expression of GABA signaling machinery in the cortically-projecting cholinergic system peaks during early development before settling at a non-zero level that is maintained through adulthood. [ABSTRACT FROM AUTHOR]

The vast majority of studies on hippocampal rhythms have been conducted on animals or humans in situations where their attention was focused on external stimuli or solving cognitive tasks. These studies formed the basis for the idea that rhythmical activity coordinates the work of neurons during information processing. However, at rest, when attention is not directed to external stimuli, brain rhythms do not disappear, although the parameters of oscillatory activity change. What is the functional load of rhythmical activity at rest? Hippocampal oscillatory activity during rest is called the non-theta state, as opposed to the theta state, a characteristic activity during active behavior.We dedicate our review to discussing the present state of the art in the research of the non-theta state. The key provisions of the review are as follows: (1) the non-theta state has its own characteristics of oscillatory and neuronal activity; (2) hippocampal non-theta state is possibly caused and maintained by change of rhythmicity of medial septal input under the influence of raphe nuclei; (3) there is no consensus in the literature about cognitive functions of the non-theta-non-ripple state; and (4) the antagonistic relationship between theta and delta rhythms observed in rodents is not always observed in humans. Most attention is paid to the non-theta-nonripple state, since this aspect of hippocampal activity has not been investigated properly and discussed in reviews. [ABSTRACT FROM AUTHOR]

Supplemental Digital Content is Available in the Text. Paraventricular hypothalamic CaMKIIα-positive neurons input to ventral of lateral septal CaMKIIα-positive neurons controls chronic visceral pain. Irritable bowel syndrome is a functional gastrointestinal disorder characterized by chronic visceral pain with complex etiology and difficult treatment. Accumulated evidence has confirmed that the sensitization of the central nervous system plays an important role in the development of visceral pain, whereas the exact mechanisms of action of the neural pathways remain largely unknown. In this study, a distinct neural circuit was identified from the paraventricular hypothalamic (PVH) to the ventral of lateral septal (LSV) region. This circuit was responsible for regulating visceral pain. In particular, the data indicated that the PVH CaMKIIα-positive neurons inputs to the LSV CaMKIIα-positive neurons were only activated by colorectal distention rather than somatic stimulations. The PVH-LSV CaMKIIα+ projection pathway was further confirmed by experiments containing a viral tracer. Optogenetic inhibition of PVH CaMKIIα+ inputs to LSV CaMKIIα-positive neurons suppressed visceral pain, whereas selective activation of the PVH-LSV CaMKIIα+ projection evoked visceral pain. These findings suggest the critical role of the PVH-LSV CaMKIIα+ circuit in regulating visceral pain. [ABSTRACT FROM AUTHOR]

Although antipsychotics' mechanisms of action have been thoroughly investigated, they have not been fully elucidated at the network level. We tested the hypothesis that acute pre-treatment with ketamine (KET) and administration of asenapine (ASE) would modulate the functional connectivity of brain areas relevant to the pathophysiology of schizophrenia, based on transcript levels of Homer1a, an immediate early gene encoding a key molecule of the dendritic spine. Sprague–Dawley rats (n = 20) were assigned to KET (30 mg/kg) or vehicle (VEH). Each pre-treatment group (n = 10) was randomly split into two arms, receiving ASE (0.3 mg/kg), or VEH. Homer1a mRNA levels were evaluated by in situ hybridization in 33 regions of interest (ROIs). We computed all possible pairwise Pearson correlations and generated a network for each treatment group. Acute KET challenge was associated with negative correlations between the medial portion of cingulate cortex/indusium griseum and other ROIs, not detectable in other treatment groups. KET/ASE group showed significantly higher inter-correlations between medial cingulate cortex/indusium griseum and lateral putamen, the upper lip of the primary somatosensory cortex, septal area nuclei, and claustrum, in comparison to the KET/VEH network. ASE exposure was associated with changes in subcortical-cortical connectivity and an increase in centrality measures of the cingulate cortex and lateral septal nuclei. In conclusion, ASE was found to finely regulate brain connectivity by modelling the synaptic architecture and restoring a functional pattern of interregional co-activation. [ABSTRACT FROM AUTHOR]

Jurassic strata are widely distributed in the eastern part of Tibet Autonomous Region, and have yielded many dinosaur bones. However, none of these specimens has been studied extensively, and some remain unprepared. Here we provide a detailed description of some new sauropod material, including several cervical vertebrae and a nearly complete scapula, recovered from the Middle Jurassic of Chaya County, East Tibet. The cervical vertebrae have short centra that bear ventral midline keels, as in many non-neosauropod sauropods such as Shunosaurus. Moreover, the cervical centra display deep lateral excavations, partitioned by a septum. The scapula has proximal and distal ends that are both expanded as in mamenchisaurids and neosauropods. However, relatively small body size and lack of fusion of neurocentral sutures in the cervical vertebrae suggest that the available material is from a juvenile, and the length of the cervical centra may have increased relative to the size of the rest of the skeleton in later ontogenetic stages. Phylogenetic analysis provides limited evidence that the new Tibetan sauropod specimen belongs to Eusauropoda, being more derived than Shunosaurus, but is basal to Mamenchisauridae. The new material provides important information on the morphological transition between Shunosaurus and mamenchisaurids, and extends the known biogeographic range of early-diverging sauropods in the Middle Jurassic of East Asia. [ABSTRACT FROM AUTHOR]