Nerve Projections Research Articles

Anatomical Study of Abdominal Wall Muscle Innervation to Optimize Retroperitoneal Vascular Approach

INTRODUCTIONDifferent surgical approaches are used in aortic surgery. Retroperitoneal approaches can result in abdominal wall weakness and flank bulging. These approaches often require dissection of the anterolateral or anteromedial muscles of the abdominal wall. During dissection, the underlying nerves are at great risk of injury, which induces significant complications in abdominal wall muscles. Few studies have been conducted to minimize the risk of injury to these nerves. OBJECTIVESThis study aims to describe the trajectory of abdominal muscle motor nerves and their relationship to ribs and other anatomical landmarks. The secondary objective is to optimize surgical approaches by preserving the nerves. METHODWe conducted 12 dissections on fresh cadavers. Nerve trajectories, communication between the intercostal nerves (9th–10th–11th) and the subcostal nerve (12th), and the distance from the nerve to the estimated projection point of intersection with the abdominal midline, umbilicus, and iliac crest was recorded. RESULTSOur dissections identified the 12th subcostal nerve as the largest nerve. The 11th intercostal nerve exhibits more accessory branches than other nerves. Multiple communications and branches were observed between the 10th and 11th intercostal nerves and between the 11th and 12th nerves in the region from the anterior axillary line to the mid-clavicular line. The estimated projection point of intersection with the midline was 7.92 ± 1.24 cm supraumbilical for the 9th intercostal nerve, 3.92 ± 1.18 cm supraumbilical for the 10th, 1.08 ± 1.52 cm at the umbilical level for the 11th, and -3.33 ± 0.83 cm infraumbilical for the subcostal nerve. The distance between the iliac crest and the iliohypogastric nerve in the lateral jackknife position was 2.54 ± 0.65 cm. The 11th nerve had an angle in relation to the rib of between -45° and -10° (average: -24.6°), and the 12th nerve had a similar angle of between -30° and 0° (average: -18.3°). For the 11th nerve, the distance was between 0 and 5.5 cm (average: 2.92 cm); for the 12th nerve, it was between 0 and 3.0 cm (average: 1.71 cm). CONCLUSIONTo preserve the 11th nerve, the optimal approach is a straight incision starting from the upper edge of the 11th rib towards the midline, 4 cm above the umbilicus; for the 12th nerve, the optimal approach is a straight incision starting from the upper edge of the 12th rib towards the midline, 1 cm below the umbilicus; for the iliohypogastric nerve, the optimal approach is an incision close to the iliac crest at a distance <1.5 cm. The estimated projection point of intersection between the nerve directions towards the midline can indicate the anatomical trajectory of nerves. A nerve projection towards the midline can provide valuable information about the anatomical location of a nerve. This study has utility in optimizing surgical approaches. A clinical study can confirm these anatomical results.

Contrast-free visualization of distal trigeminal nerve segments using MR neurography.

The 3-dimensional cranial nerve imaging (CRANI) sequence may assist visualization of anatomical details of extraforaminal cranial nerves and aid in clinical diagnosis and preoperative planning. In this study, we investigated the feasibility of using a combined CRANI and magnetization-prepared rapid-acquisition gradient-echo (MPRAGE) imaging protocol to comprehensively identify trigeminal nerve projections. We evaluated the detection of distal regions of three branches of the ophthalmic nerve (V1), three branches of the maxillary nerve (V2), and five branches of the mandibular nerve (V3) in seven healthy adult subjects, with and without contrast injection. Nerve branches were rated on a 5-point scale by three observers. Interobserver reliability was studied using weighted kappa statistics and percentage agreement. Among V1 and V2 branches, the frontal nerve and infraorbital nerve were most successfully identified (average rating of 3.9, agreement >80%) in precontrast MPRAGE images. In V3 branches, lingual and inferior alveolar nerves were most successfully identified (average rating of 3.9, agreement >80%) in precontrast CRANI images, with an excellent average rating. In all cases except one, interobserver reliability was rated good to excellent. The buccal nerve was the only branch with a low average interobserver rating. Gadolinium contrast did not improve nerve segment visualization in our study. This may relate to the specific anatomic regions assessed, gadolinium dose, postcontrast image timing, and lack of pathology. A combined CRANI and MPRAGE protocol can be combined to visualize distal branches of V1, V2, and V3 and has potential for clinical use.

Differences of ocular oscillations and neuro-retinal structures in patients with nystagmus caused by GPR143 and FRMD7 gene variants.

Mutations of G protein-coupled receptor 143 (GPR143) and FERM domain containing 7 (FRMD7) may result in congenital nystagmus (CN) in the first 6 months of life. We aimed to compare the differences in ocular oscillations between patients with these two gene mutations as well as the functional and structural changes in their retinas and visual pathways. Medical records were retrospectively reviewed to identify patients of congenital nystagmus with confirmed mutations in either GPR143 or FMRD7 genes from January 2018 to May 2023. The parameters of the ocular oscillations were recorded using Eyelink 1000 Plus. The retinal structure and function were evaluated using optical coherence tomography and multi-focal electroretinography (mERG). The visual pathway and optical nerve projection were evaluated using visual evoked potentials. The next-generation sequencing technique was used to identify the pathogenic variations in the disease-causing genes for CN. Twenty nystagmus patients of GPR143 and 21 patients of FMRD7 who had been confirmed by molecular testing between January 2018 and May 2023 were included. Foveal hypoplasia was detected only in patients with the GPR143 pathogenic variant. mERG examination showed a flat response topography in the GPR143 group compared to the FRMD7 group. VEP showed that bilateral amplitude inconsistency was detected only in the patients with GPR143 gene mutation. The amplitude and frequency of the ocular oscillations were not found to differ between patients with two different genetic mutations. Although the etiology and molecular mechanisms are completely different between CN patients, they may have similar ocular oscillations. A careful clinical examination and electrophysiological test will be helpful in making a differential diagnosis. Our novel identified variants will further expand the spectrum of the GPR143 and FRMD7 variants.

Tissue-Targeted Transcriptomics Reveals SEMA3D Control of Hypoglossal Nerve Projection to Mouse Tongue Primordia.

The mouse hypoglossal nerve originates in the occipital motor nuclei at embryonic day (E)10.5 and projects a long distance, reaching the vicinity of the tongue primordia, the lateral lingual swellings, at E11.5. However, the details of how the hypoglossal nerve correctly projects to the primordia are poorly understood. To investigate the molecular basis of hypoglossal nerve elongation, we used a novel transcriptomic approach using the ROKU method. The ROKU algorithm identified 3825 genes specific for lateral lingual swellings at E11.5, of which 34 genes were predicted to be involved in axon guidance. Ingenuity Pathway Analysis-assisted enrichment revealed activation of the semaphorin signaling pathway during tongue development, and quantitative PCR showed that the expressions of Sema3d and Nrp1 in this pathway peaked at E11.5. Immunohistochemistry detected NRP1 in the hypoglossal nerve and SEMA3D as tiny granules in the extracellular space beneath the epithelium of the tongue primordia and in lateral and anterior regions of the mandibular arch. Fewer SEMA3D granules were localized around hypoglossal nerve axons and in the space where they elongated. In developing tongue primordia, tissue-specific regulation of SEMA3D might control the route of hypoglossal nerve projection via its repulsive effect on NRP1.

Distribution of insulin in primate brain following nose-to-brain transport.

Nose-to-brain (N2B) insulin delivery has potential for Alzheimer's disease (AD) therapy. However, clinical implementation has been challenging without methods to follow N2B delivery non-invasively. Positron emission tomography (PET) was applied to measure F-18-labeled insulin ([18F]FB-insulin) from intranasal dosing to brain uptake in non-human primates following N2B delivery. [18F]FB-insulin was prepared by reacting A1,B29-di(tert-butyloxycarbonyl)insulin with [18F]-N-succinimidyl-4-fluorobenzoate. Three methods of N2B delivery for [18F]FB-insulin were compared - delivery as aerosol via tubing (rhesus macaque, n = 2), as aerosol via preplaced catheter (rhesus macaque, n = 3), and as solution via preplaced catheter (cynomolgus macaque, n = 3). Following dosing, dynamic PET imaging (120 min) quantified delivery efficiency to the nasal cavity and whole brain. Area under the time-activity curve was calculated for 46 regions of the cynomolgus macaque brain to determine regional [18F]FB-insulin levels. Liquid instillation of [18F]FB-insulin by catheter outperformed aerosol methods for delivery to the subject (39.89% injected dose vs 10.03% for aerosol via tubing, 0.17% for aerosol by catheter) and subsequently to brain (0.34% injected dose vs 0.00020% for aerosol via tubing, 0.05% for aerosol by catheter). [18F]FB-insulin was rapidly transferred across the cribriform plate to limbic and frontotemporal areas responsible for emotional and memory processing. [18F]FB-insulin half-life was longer in olfactory nerve projection sites with high insulin receptor density compared to the whole brain. The catheter-based liquid delivery approach combined with PET imaging successfully tracked the fate of N2B [18F]FB-insulin and is thought to be broadly applicable for assessments of other therapeutic agents. This method can be rapidly applied in humans to advance clinical evaluation of N2B insulin as an AD therapeutic. [18F]FB-insulin passage across the cribriform plate was detected by PET.Intranasal [18F]FB-insulin reached the brain within 13 min.[18F]FB-insulin activity was highest in emotional and memory processing regions.Aerosol delivery was less efficient than liquid instillation by preplaced catheter.Insulin delivery to the cribriform plate was critical for arrival in the brain.

In vivo tracing of the ascending vagal projections to the brain with manganese enhanced magnetic resonance imaging.

The vagus nerve, the primary neural pathway mediating brain-body interactions, plays an essential role in transmitting bodily signals to the brain. Despite its significance, our understanding of the detailed organization and functionality of vagal afferent projections remains incomplete. In this study, we utilized manganese-enhanced magnetic resonance imaging (MEMRI) as a non-invasive and in vivo method for tracing vagal nerve projections to the brainstem and assessing their functional dependence on cervical vagus nerve stimulation (VNS). Manganese chloride solution was injected into the nodose ganglion of rats, and T1-weighted MRI scans were performed at both 12 and 24 h after the injection. Our findings reveal that vagal afferent neurons can uptake and transport manganese ions, serving as a surrogate for calcium ions, to the nucleus tractus solitarius (NTS) in the brainstem. In the absence of VNS, we observed significant contrast enhancements of around 19-24% in the NTS ipsilateral to the injection side. Application of VNS for 4 h further promoted nerve activity, leading to greater contrast enhancements of 40-43% in the NTS. These results demonstrate the potential of MEMRI for high-resolution, activity-dependent tracing of vagal afferents, providing a valuable tool for the structural and functional assessment of the vagus nerve and its influence on brain activity.

AI Machine Learning Technique Characterizes Potential Markers of Depression in Two Animal Models of Depression.

(1) Background: there is an urgent clinical need for rapid and effective antidepressants. (2) Methods: We employed proteomics to profile proteins in two animal models (n = 48) of Chronic Unpredictable Stress and Chronic Social Defeat Stress. Additionally, partial least squares projection to latent structure discriminant analysis and machine learning were used to distinguish the models and the healthy control, extract and select protein features and build biomarker panels for the identification of different mouse models of depression. (3) Results: The two depression models were significantly different from the healthy control, and there were common changes in proteins in the depression-related brain regions of the two models; i.e., SRCN1 was down-regulated in the dorsal raphe nucleus in both models of depression. Additionally, SYIM was up-regulated in the medial prefrontal cortex in the two depression models. Bioinformatics analysis suggested that perturbed proteins are involved in energy metabolism, nerve projection, etc. Further examination confirmed that the trends of feature proteins were consistent with mRNA expression levels. (4) Conclusions: To the best of our knowledge, this is the first study to probe new targets of depression in multiple brain regions of two typical models of depression, which could be targets worthy of study.

The Structure, Function and Regulation of Protein Tyrosine Phosphatase Receptor Type J and Its Role in Diseases.

Protein tyrosine phosphatase receptor type J (PTPRJ), also known as DEP-1, HPTPη, or CD148, belongs to the R3 subfamily of receptor protein tyrosine phosphatases (RPTPs). It was first identified as an antioncogene due to its protein level being significantly downregulated in most epithelial tumors and cancer cell lines (e.g., colon, lung, thyroid, breast, and pancreas). PTPRJ regulates mouse optic nerve projection by inhibiting the phosphorylation of the erythropoietin-producing hepatocellular carcinoma (Eph) receptor and abelson murine leukemia viral oncogene homolog 1 (c-Abl). PTPRJ is crucial for metabolism. Recent studies have demonstrated that PTPRJ dephosphorylates JAK2 at positions Y813 and Y868 to inhibit leptin signaling. Akt is more phosphorylated at the Ser473 and Thr308 sites in Ptprj-/- mice, suggesting that PTPRJ may be a novel negative regulator of insulin signaling. PTPRJ also plays an important role in balancing the pro- and anti-osteoclastogenic activity of the M-CSF receptor (M-CSFR), and in maintaining NFATc1 expression during the late stages of osteoclastogenesis to promote bone-resorbing osteoclast (OCL) maturation. Furthermore, multiple receptor tyrosine kinases (RTKs) as substrates of PTPRJ are probably a potential therapeutic target for many types of diseases, such as cancer, neurodegenerative diseases, and metabolic diseases, by inhibiting their phosphorylation activity. In light of the important roles that PTPRJ plays in many diseases, this review summarizes the structural features of the protein, its expression pattern, and the physiological and pathological functions of PTPRJ, to provide new ideas for treating PTPRJ as a potential therapeutic target for related metabolic diseases and cancer.

Loss of the chromatin remodeler CHD7 impacts glial cells and myelination in the mouse cochlear spiral ganglion

CHARGE syndrome is a multiple anomaly developmental disorder characterized by a variety of sensory deficits, including sensorineural hearing loss of unknown etiology. Most cases of CHARGE are caused by heterozygous pathogenic variants in CHD7, the gene encoding Chromodomain DNA-binding Protein 7 (CHD7), a chromatin remodeler important for the development of neurons and glial cells. Previous studies in the Chd7Gt/+ mouse model of CHARGE syndrome showed substantial neuron loss in the early stages of the developing inner ear that are compensated for by mid-gestation. In this study, we sought to determine if early developmental delays caused by Chd7 haploinsufficiency affect neurons, glial cells, and inner hair cell innervation in the mature cochlea. Analysis of auditory brainstem response recordings in Chd7Gt/+ adult animals showed elevated thresholds at 4 kHz and 16 kHz, but no differences in ABR Wave I peak latency or amplitude compared to wild type controls. Proportions of neurons in the Chd7Gt/+ adult spiral ganglion and densities of nerve projections from the spiral ganglion to the organ of Corti were not significantly different from wild type controls. Inner hair cell synapse formation also appeared unaffected in mature Chd7Gt/+ cochleae. However, histological analysis of adult Chd7Gt/+ cochleae revealed diminished satellite glial cells and hypermyelinated Type I spiral ganglion axons. We characterized the expression of CHD7 in developing inner ear glia and found CHD7 to be expressed during a tight window of inner ear development at the Schwann cell precursor stage at E9.5. While cochlear neurons appear to differentiate normally in the setting of Chd7 haploinsufficiency, our results suggest an important role for CHD7 in glial cells in the inner ear. This study highlights the dynamic nature of CHD7 activity during inner ear development in mice and contributes to understanding CHARGE syndrome pathology.

Anatomy of the vesicovaginal fascia and its relation to branches of the inferior hypogastric plexus.

The inferior hypogastric plexus (IHP) lies in the extraperitoneal pelvis, and supplies branches to pelvic and perineal viscera. In men, the rectoprostatic fascia (Denonvillier's fascia) forms a distinct double fascial layer between the seminal glands and the rectum. The hypogastric nerve projections to the prostate and seminal glands run anterior to this. An analagous fascial layer in women between the vagina and cervix posteriorly and the urinary bladder anteriorly has recently been described. The purpose of this study was to examine the anatomy of the vesicovaginal fascia (VVF) and to determine its relationship to the anterior branches of the IHP. This dissection study examined the fascial layers between the posterior urinary bladder and anterior vagina/cervix (VVF) in 15 female embalmed cadavers and three fresh specimens. Anterior branches of the IHP were identified and followed distally. The relationship between these nerve projections and the VVF was examined. In 16 dissection, the VVF was identified as a complete fascial plane extending beneath the vesicouterine pouch to the neck of the bladder inferiorly and to the endopelvic fascia laterally. Anterior projections from the hypogastric nerves and IHP maintained an extraperitoneal course passing anteriorly to the VVF towards the urinary bladder The VVF is a distinct fascial structure and projections of the hypogastric nerves pass anterior to this. This may have implications for nerve sparing hysterectomy.

Transcutaneous vagus nerve stimulation (tVNS) in stroke: the evidence, challenges and future directions.

Stroke is one of the leading causes of death and disability globally. A significant proportion of stroke survivors are left with long term neurological deficits that have a detrimental effect on personal wellbeing and wider socioeconomic impacts. As such, there is an unmet need for novel therapies that improve neurological recovery after stroke. Invasive vagus nerve stimulation (VNS) paired with rehabilitation has been shown to improve upper limb motor function in chronic stroke. However, invasive VNS requires a surgical procedure and therefore may not be suitable for all stroke patients. Non-invasive, transcutaneous VNS (tVNS) via auricular vagus nerve stimulation in the ear (taVNS) and cervical vagus nerve stimulation in the neck (tcVNS) have been shown to activate similar vagal nerve projections in the central nervous system to invasive VNS. A number of pre-clinical studies indicate that tVNS delivered in acute middle cerebral artery occlusion reduces infarct size through anti-inflammatory effects, reduced excitotoxicity and increased blood-brain barrier integrity. Longer term effects of tVNS in stroke that may mediate neuroplasticity include microglial polarisation, angiogenesis and neurogenesis. Pilot clinical trials of taVNS indicate that taVNS paired with rehabilitation may improve upper limb motor and sensory function in patients with chronic stroke. In this review, we summarise and critically appraise the current pre-clinical and clinical evidence, outline the major ongoing clinical trials and detail the challenges and future directions regarding tVNS in acute and chronic stroke.

Prostaglandin analog effects on cerebrospinal fluid reabsorption via nasal mucosa.

Cerebrospinal fluid (CSF) outflow has been demonstrated along nasal lymphatics via olfactory nerve projections; flow may be increased by stimulating lymphatic contractility using agents such as noradrenaline and the thromboxane A2 analog U46619. Lymphatics elsewhere in the body show increased contractility upon exposure to the prostaglandin F2alpha analog isoprostane-8-epi-prostaglandin. We investigated the ability of ophthalmic prostaglandin F2alpha analogs to increase CSF outflow when applied to the nasal mucosa by inhalation. Latanoprost (0.1, 0.5, or 1mg/ml), bimatoprost (0.3 or 3mg/ml), travoprost (0.04 or 0.4mg/ml), latanoprostene bunod (0.24 or 2.4mg/ml), tafluprost (0.25 or 2.5mg/ml), or control vehicle (10% DMSO) was administered to awake adult C57B/6 mice by nasal inhalation of 2μl droplets. Multiday dosing (daily for 3 days) of latanoprost also was evaluated. A total of 81 animals were studied including controls. General anesthesia was induced by injection, and fluorescent tracer (AlexaFluor647-labelled ovalbumin) was injected under stereotaxic guidance into the right lateral ventricle. Nasal turbinate tissue was harvested and homogenized after 1 hour for tracer detection by ELISA and fluorometric analysis. Inhalation of latanoprost 0.5mg/ml and 1mg/ml led to a 11.5-fold increase in tracer recovery from nasal turbinate tissues compared to controls (3312 pg/ml vs 288 pg/ml, p<0.001 for 0.5mg/ml; 3355 pg/ml vs 288 pg/ml, p<0.001 for 1mg/ml), while latanoprost 0.1 mg/ml enhanced recovery 6-fold (1713 pg/ml vs 288 pg/ml, p<0.01). Tafluprost 0.25mg/ml and bimatoprost 0.3mg/ml showed a modest (1.4x, p<0.05) effect, and the remaining agents showed no significant effect on tracer recovery. After 3 days of daily latanoprost treatment and several hours after the last dose, a persistently increased recovery of tracer was found. Prostaglandin F2alpha analogs delivered by nasal inhalation resulted in increased nasal recovery of a CSF fluorescent tracer, implying increased CSF outflow via the nasal lymphatics. The greatest effect, partially dose-dependent, was observed using latanoprost. Further studies are needed to determine the efficacy of these agents in reducing ICP in short and long-term applications.

Brain signaling dynamics after vagus nerve stimulation

The vagus nerve projects to a well-defined neural circuit via the nucleus tractus solitarii (NTS) and its stimulation elicits a wide range of metabolic, neuromodulatory, and behavioral effects. Transcutaneous vagus nerve stimulation (tVNS) has been established as a promising technique to non-invasively alter brain function. However, the precise dynamics elicited by tVNS in humans are still largely unknown. Here, we performed fMRI with concurrent right-sided tVNS (vs. sham) following a randomized cross-over design (N = 40). First, to unravel the temporal profile of tVNS-induced changes in the NTS, we compared fMRI time series to canonical profiles for stimulation ON and OFF cycles. Model comparisons indicated that NTS time series were best fit by block-wise shifts in signal amplitude with stimulation ON and OFF estimates being highly correlated. Therefore, we compared stimulation (ON + OFF) versus baseline phases and found that tVNS increased fMRI BOLD activation in the NTS, but this effect was dependent on sufficient temporal signal-to-noise ratio (tSNR) in the mask. Second, to identify the spatiotemporal evolution of tVNS-induced changes in the brain, we examined lagged co-activation patterns and phase coherence. In contrast to our hypothesis, tVNS did not alter dynamic functional connectivity after correction for multiple comparisons. Third, to establish a positive control for future research, we measured changes in gastric myoelectrical frequency via an electrogastrogram. Again, in contrast to our hypothesis, tVNS induced no changes in gastric frequency. Collectively, our study provides evidence that tVNS can perturb brain signaling in the NTS, but these effects are dependent on tSNR and require precise localization. In light of an absence of acute tVNS-induced effects on dynamic functional connectivity and gastric motility, we discuss which steps are necessary to advance future research on afferent and efferent effects of tVNS.

Sensitivity of olfactory sensory neurons to food cues is tuned to nutritional states by Neuropeptide Y signaling

Modulation of sensory perception by homeostatic feedback from physiological states is central to innate purposive behaviors. Olfaction is an important predictive modality for feeding-related behaviors and its modulation has been associated with hunger-satiety states. However, the mechanisms mapping internal states to chemosensory processing in order to modify behavior are poorly understood. In the zebrafish olfactory epithelium, a subset of olfactory sensory neurons (OSNs) and the terminal nerve projections express neuropeptide Y (NPY). Using a combination of neuronal activity and behavioral evaluation, we find that NPY signaling in the peripheral olfactory system of zebrafish is correlated with its nutritional state and is both necessary and sufficient for the olfactory perception of food-related odorants. NPY activity dynamically modulates the microvillar OSN activation thresholds and acts cooperatively with amino acid signaling resulting in a switch-like increase in OSN sensitivity in starved animals. We suggest that cooperative activation of phospholipase C by convergent signaling from NPY and amino acid receptors is central to this heightened sensitivity. This study provides ethologically relevant, physiological evidence for NPY signaling in the modulation of OSN sensitivity to food-associated amino acid cues. We demonstrate sensory gating directly at the level of OSNs and identify a novel mechanistic framework for tuning olfactory sensitivity to prevailing energy states. Cover Image for this issue:https://doi.org/10.1111/jnc.15091.

Loss-of-function variants in SEMA3F and PLXNA3 encoding semaphorin-3F and its receptor plexin-A3 respectively cause idiopathic hypogonadotropic hypogonadism

PurposeIdiopathic hypogonadotropic hypogonadism (IHH) is characterized by absent puberty and subsequent infertility due to gonadotropin-releasing hormone (GnRH) deficiency. IHH can be accompanied by normal or compromised olfaction (Kallmann syndrome). Several semaphorins are known potent modulators of GnRH, olfactory, and vomeronasal system development. In this study, we investigated the role of Semaphorin-3F signaling in the etiology of IHH. MethodsWe screened 216 IHH patients by exome sequencing. We transiently transfected HEK293T cells with plasmids encoding wild type (WT) or corresponding variants to investigate the functional consequences. We performed fluorescent IHC to assess SEMA3F and PLXNA3 expression both in the nasal region and at the nasal/forebrain junction during the early human fetal development. ResultsWe identified ten rare missense variants in SEMA3F and PLXNA3 in 15 patients from 11 independent families. Most of these variants were predicted to be deleterious by functional assays. SEMA3F and PLXNA3 are both expressed along the olfactory nerve and intracranial projection of the vomeronasal nerve/terminal nerve. PLXNA1-A3 are expressed in the early migratory GnRH neurons. ConclusionSEMA3F signaling through PLXNA1-A3 is involved in the guidance of GnRH neurons and of olfactory and vomeronasal nerve fibers in humans. Overall, our findings suggest that Semaphorin-3F signaling insufficiency contributes to the pathogenesis of IHH.

Traumatic Optic Neuropathy Is Associated with Visual Impairment, Neurodegeneration, and Endoplasmic Reticulum Stress in Adolescent Mice.

Traumatic brain injury (TBI) results in a number of impairments, often including visual symptoms. In some cases, visual impairments after head trauma are mediated by traumatic injury to the optic nerve, termed traumatic optic neuropathy (TON), which has few effective options for treatment. Using a murine closed-head weight-drop model of head trauma, we previously reported in adult mice that there is relatively selective injury to the optic tract and thalamic/brainstem projections of the visual system. In the current study, we performed blunt head trauma on adolescent C57BL/6 mice and investigated visual impairment in the primary visual system, now including the retina and using behavioral and histologic methods at new time points. After injury, mice displayed evidence of decreased optomotor responses illustrated by decreased optokinetic nystagmus. There did not appear to be a significant change in circadian locomotor behavior patterns, although there was an overall decrease in locomotor behavior in mice with head injury. There was evidence of axonal degeneration of optic nerve fibers with associated retinal ganglion cell death. There was also evidence of astrogliosis and microgliosis in major central targets of optic nerve projections. Further, there was elevated expression of endoplasmic reticulum (ER) stress markers in retinas of injured mice. Visual impairment, histologic markers of gliosis and neurodegeneration, and elevated ER stress marker expression persisted for at least 30 days after injury. The current results extend our previous findings in adult mice into adolescent mice, provide direct evidence of retinal ganglion cell injury after head trauma and suggest that axonal degeneration is associated with elevated ER stress in this model of TON.

CAPS2 Deficiency Impairs the Release of the Social Peptide Oxytocin, as Well as Oxytocin-Associated Social Behavior.

Ca2+-dependent activator protein for secretion 2 (CAPS2) regulates dense-core vesicle (DCV) exocytosis to facilitate peptidergic and catecholaminergic transmitter release. CAPS2 deficiency in mice has mild neuronal effects but markedly impairs social behavior. Rare de novo Caps2 alterations also occur in autism spectrum disorder, although whether CAPS2-mediated release influences social behavior remains unclear. Here, we demonstrate that CAPS2 is associated with DCV exocytosis-mediated release of the social interaction modulatory peptide oxytocin (OXT). CAPS2 is expressed in hypothalamic OXT neurons and localizes to OXT nerve projection and OXT release sites, such as the pituitary. Caps2 KO mice exhibited reduced plasma albeit increased hypothalamic and pituitary OXT levels, indicating insufficient release. OXT neuron-specific Caps2 conditional KO supported CAPS2 function in pituitary OXT release, also affording impaired social interaction and recognition behavior that could be ameliorated by exogenous OXT administered intranasally. Thus, CAPS2 appears critical for OXT release, thereby being associated with social behavior.SIGNIFICANCE STATEMENT The role of the neuropeptide oxytocin in enhancing social interaction and social bonding behavior has attracted considerable public and neuroscientific attention. A central issue in oxytocin biology concerns how oxytocin release is regulated. Our study provides an important insight into the understanding of oxytocin-dependent social behavior from the perspective of the CAPS2-regulated release mechanism.

Somatosensory-Auditory Processing of the Fifth Cervical Nerve in Tinnitus.

Cervical spinal nerve projections influence auditory responses and play a role in the pathology of tinnitus. The intention of our research was to lay down the amenity of treatment of the fifth (C5) cervical nerve to lessen tinnitus and to obtain specifications associated with a long-term effect of this method. Subjects were 54 tinnitus patients who were treated with infiltration of the fifth cervical nerve. Clinical data form these patients were reviewed retrospectively. An independent perceiver evaluated the long-term effect of the therapy by telephone interview. Treating the C5 is beneficial for 30% of the tinnitus patients. The majority of patients with a beneficial result rated the tinnitus reduction of 50% or more. At 9 months, half of the patients still had benefit. Less hearing at 1 kHz together with a large spur in front of the fifth cervical vertebrae forecasted a beneficial effect of the C5 therapy on tinnitus at 7 weeks. Treating cervical spine complaints can lessen tinnitus. Therapy of C5 resulted in less tinnitus for 30% of the tinnitus patients. However, selection of tinnitus patients with an evident spur in front of the fifth cervical vertebrae together with a less hearing at 1 kHz will improve the success rate of C5 therapy.

Cervical Nerve Projections to the Auditory Pathway in Tinnitus.

Cervical spinal nerves project to the auditory system and take part in the pathology of tinnitus. The intention of our research was to estimate the outcome of treatment of C6 and C7 to lessen tinnitus intensity and to find criteria for a long-term success. Subjects were 78 tinnitus patients who were treated with infiltration of the sixth and seventh cervical nerve. Clinical data form these patients were reviewed retrospectively. An independent perceiver evaluated the long-term effect of the therapy by telephone interview. In a cohort of tinnitus patients, 18% had less tinnitus after treatment of C6 and C7. The majority of the patients announced a moderate easing of their tinnitus. At 2,5 months, half of the patients with a positive response still had benefit. The combination of hearing loss at 8 kHz and the highness of the intervertebral disc at C4-C5 forecasted a beneficial result of therapy of C6 and C7 with a longer period of relief. Treating afferent cervical nerves can lessen tinnitus. Therapy of C6 and C7 caused less tinnitus for 18% of the tinnitus patients. Especially patients with no hearing loss at 8 kHz and no disc degeneration at C4-C5 forecasted a beneficial result of therapy of C6 and C7 on tinnitus with a longer period of relief.

Macroanatomic, light and scanning electron microscopic structure of the pecten oculi in northern bald ibis (Geronticus eremita).

Eyes are the most primarily required sensory organs during the migration of migratory birds and Northern Bald Ibises (Geronticus eremita) are known to make long migrations. This study examined for the first time the structure of pecten oculi in northern bald ibises by using macroscopic anatomy as well as light and electron microscopic methods. In the study 20 eye globes from 10 adult bald ibises were used. The pecten was of pleated type. As in most bird species, it was located on the optic nerve head and projects into the vitreous from the optic nerve head. The wider basal part was observed to attached to retina and its free apical part was found in camera vitrea bulbi embedded in corpus vitreum. The pecten had 13-14 accordion like pleats lying between the basal and apical parts. In addition to arterial and venous vessels, numerous capillary vessels as well as melanocytes were observed within each pleat. The bridge binding the pleats at the apical part showed a stronger pigmentation compared to other parts of the pecten. The results of the study indicated that the general morphology of pecten oculi in northern bald ibises which is a migratory bird species were similar to that in other diurnal bird species.