Oxytocin signaling is necessary for synaptic maturation of adult-born neurons.

Neural circuit plasticity and sensory response dynamics depend on forming new synaptic connections. Despite recent advances toward understanding the consequences of circuit plasticity, the mechanisms driving circuit plasticity are unknown. Adult-born neurons within the olfactory bulb have proven to be a powerful model for studying circuit plasticity, providing a broad and accessible avenue into neuron development, migration, and circuit integration. We and others have shown that efficient adult-born neuron circuit integration hinges on presynaptic activity in the form of diverse signaling peptides. Here, we demonstrate a novel oxytocin-dependent mechanism of adult-born neuron synaptic maturation and circuit integration. We reveal spatial and temporal enrichment of oxytocin receptor expression within adult-born neurons in the murine olfactory bulb, with oxytocin receptor expression peaking during activity-dependent integration. Using viral labeling, confocal microscopy, and cell type-specific RNA-seq, we demonstrate that oxytocin receptor signaling promotes synaptic maturation of newly integrating adult-born neurons by regulating their morphological development and expression of mature synaptic AMPARs and other structural proteins.

Alzheimer's disease risk gene CD2AP is a dose-sensitive determinant of synaptic structure and plasticity.

CD2-Associated protein (CD2AP) is a candidate susceptibility gene for Alzheimer's disease, but its role in the mammalian central nervous system remains largely unknown. We show that CD2AP protein is broadly expressed in the adult mouse brain, including within cortical and hippocampal neurons, where it is detected at pre-synaptic terminals. Deletion of Cd2ap altered dendritic branching and spine density, and impaired ubiquitin-proteasome system activity. Moreover, in mice harboring either one or two copies of a germline Cd2ap null allele, we noted increased paired-pulse facilitation at hippocampal Schaffer-collateral synapses, consistent with a haploinsufficient requirement for pre-synaptic release. Whereas conditional Cd2ap knockout in the brain revealed no gross behavioral deficits in either 3.5- or 12-month-old mice, Cd2ap heterozygous mice demonstrated subtle impairments in discrimination learning using a touchscreen task. Based on unbiased proteomics, partial or complete loss of Cd2ap triggered perturbation of proteins with roles in protein folding, lipid metabolism, proteostasis, and synaptic function. Overall, our results reveal conserved, dose-sensitive requirements for CD2AP in the maintenance of neuronal structure and function, including synaptic homeostasis and plasticity, and inform our understanding of possible cell-type specific mechanisms in Alzheimer's Disease.

Treatment of ventral neurenteric cyst at the cervicothoracic junction with the anterior approach in a pediatric patient: illustrative case.

BACKGROUND: Neurenteric cysts are rare congenital lesions from heterotopic endodermal tissue, often presenting with radiculopathy or myelopathy in young adults. Gross-total resection is curative; however, the surgical approach remains widely debated for cervicothoracic cases. While the posterior approach is common, the anterior approach has had success in adults. The authors present the first pediatric case of anterior corpectomy with gross-total resection of a cervicothoracic neurenteric cyst alongside an extensive literature review. OBSERVATIONS: A 10-year-old male, who had undergone a previous cyst resection via a posterior approach at an outside institution, presented with back pain, paraplegia, and urinary incontinence. Magnetic resonance imaging of the spine revealed a ventral hyperintense cyst at C7-T1 consistent with a neurenteric cyst. An anterior approach involving C7 and T1 corpectomies was performed, including intradural exploration leading to complete cyst resection. This was followed by the placement of an expandable cage and anterior and posterior fixation with arthrodesis for stabilization. The patient's symptoms completely resolved after surgery, and there has been no recurrence. LESSONS: The anterior approach is a viable option for cervicothoracic neurenteric cyst resection in the pediatric population and can aid in gross-total resection by providing better lesion visualization. More studies are needed on long-term outcomes of the anterior approach in pediatric populations. https://thejns.org/doi/10.3171/CASE24120.

Sensory Symptoms Across the Lifespan in People With Cerebral Palsy.

BACKGROUND: To estimate the prevalence of sensory symptoms in people with cerebral palsy (CP) across the lifespan. METHODS: In this cross-sectional study, the self-reported Sensory Processing Scale Inventory (SPS-I) was administered via Research Electronic Data Capture (REDCap) between February 1, 2022, and August 15, 2022, to people with CP or their caregivers enrolled in the online MyCP Community Registry. We determined the association between SPS-I scores and age (Pearson correlation) and functional status as assessed using five validated functional classification systems for CP (analysis of variance [ANOVA]). We hypothesized that sensory symptoms would differ between younger and older individuals with CP. RESULTS: Of 155 responses (28% response rate, age one to 76 years, 34% male), 97% reported at least one bothersome sensory symptom. Total sensory symptoms decreased with age (R2 = 0.12, P < 0.0001), driven by decreases in hyposensitivity symptoms (R2 = 0.32, P < 0.0001), primarily tactile hyposensitivity (R2 = 0.29, P < 0.0001). Sensory symptoms increased with greater functional impairment across all functional domains (ANOVA, P < 0.0001). However, the age-specific decrease in hyposensitivities was most pronounced in people with the greatest gross motor functional impairment (R2 = 0.70, P = 0.0004). CONCLUSION: Our findings suggest that hyposensitivity, primarily tactile sensitivity, decreases with age in people with CP. Future work should assess whether decreased hyposensitivity contributes to other age-related changes in CP like increased pain.

Cholinergic Basal Forebrain Connectivity to the Basolateral Amygdala Modulates Food Intake.

Obesity results from excessive caloric input associated with overeating and presents a major public health challenge. The hypothalamus has received significant attention for its role in governing feeding behavior and body weight homeostasis. However, extrahypothalamic brain circuits also regulate appetite and consumption by altering sensory perception, motivation, and reward. We recently discovered a population of basal forebrain cholinergic (BFc) neurons that regulate appetite suppression. Through viral tracing methods in the mouse model, we found that BFc neurons densely innervate the basolateral amygdala (BLA), a limbic structure involved in motivated behaviors. Using channelrhodopsin-assisted circuit mapping, we identified cholinergic responses in BLA neurons following BFc circuit manipulations. Furthermore, in vivo acetylcholine sensor and genetically encoded calcium indicator imaging within the BLA (using GACh3 and GCaMP, respectively) revealed selective response patterns of activity during feeding. Finally, through optogenetic manipulations in vivo, we found that increased cholinergic signaling from the BFc to the BLA suppresses appetite and food intake. Together, these data support a model in which cholinergic signaling from the BFc to the BLA directly influences appetite and feeding behavior.

Co-transmitting interneurons in the mouse olfactory bulb regulate olfactory detection and discrimination.

Co-transmission of multiple neurotransmitters from a single neuron increases the complexity of signaling information within defined neuronal circuits. Superficial short-axon cells in the olfactory bulb release both dopamine and γ-aminobutyric acid (GABA), yet the specific targets of these neurotransmitters and their respective roles in olfaction have remained unknown. Here, we implement intersectional genetics in mice to selectively block GABA or dopamine release from superficial short-axon cells to identify their distinct cellular targets, impact on circuit function, and behavioral contribution of each neurotransmitter toward olfactory behaviors. We provide functional and anatomical evidence for divergent superficial short-axon cell signaling onto downstream neurons to shape patterns of mitral cell firing that contribute to olfactory-related behaviors.

Endoscopic Anterior Lumbar Interbody Fusion: Systematic Review and Meta-Analysis.

Laparoscopic anterior lumbar interbody fusion (L-ALIF), which employs laparoscopic cameras to facilitate a less invasive approach, originally gained traction during the 1990s but has subsequently fallen out of favor. As the envelope for endoscopic approaches continues to be pushed, a recurrence of interest in laparoscopic and/or endoscopic anterior approaches seems possible. Therefore, evaluating the current evidence base in regard to this approach is of much clinical relevance. To this end, a systematic literature search was performed according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines using the following keywords: "(laparoscopic OR endoscopic) AND (anterior AND lumbar)." Out of the 441 articles retrieved, 22 were selected for quantitative analysis. The primary outcome of interest was the radiographic fusion rate. The secondary outcome was the incidence of perioperative complications. Meta-analysis was performed using RStudio's "metafor" package. Of the 1,079 included patients (mean age, 41.8±2.9 years), 481 were males (44.6%). The most common indication for L-ALIF surgery was degenerative disk disease (reported by 18 studies, 81.8%). The mean follow-up duration was 18.8±11.2 months (range, 6-43 months). The pooled fusion rate was 78.9% (95% confidence interval [CI], 68.9-90.4). Complications occurred in 19.2% (95% CI, 13.4-27.4) of L-ALIF cases. Additionally, 7.2% (95% CI, 4.6-11.4) of patients required conversion from L-ALIF to open surgery. Although L-ALIF does not appear to be supported by studies available in the literature, it is important to consider the context from which these results have been obtained. Even if these results are taken at face value, the failure of endoscopy to have a role in the ALIF approach does not mean that it should not be incorporated in posterior approaches.

Skin, Hair, and Nail Supplements: Marketing and Labeling Concerns.

Background and objective Dietary supplements advertised to "boost collagen" or for "skin, hair, and nail" health are becoming increasingly popular, despite a lack of evidence to support their use. These products are not regulated by the United States (U.S.) Food and Drug Administration (FDA), and hence there is no centralized database listing current products. The goal of this study was to document and examine the labeling and marketing methods of these products. Methods Supplements including the words "glow," "beauty," "skin," "hair," or "nails" on the label were included in the sample. Seven stores within a 3-mile radius were included. Results A total of 176 unique supplements were identified. It was found that most products lacked independent testing; many utilized outdated daily values (DVs) of nutrients. Some had confusing dosing instructions, and most products made health-related marketing claims. Conclusion Dermatologists and primary care providers should be aware of the marketing claims commonly made by these products. Patients should be educated that these claims are generally not verified by independent testing agencies, the U.S. FDA, or by high-quality randomized control trials.

Safety Concerns of Skin, Hair and Nail Supplements in Retail Stores.

BACKGROUND: Dietary supplements promoted for "skin, hair, and nail" health are becoming increasingly popular, although there is a lack of regulatory oversight. As no centralized database or repository for these supplements is available, the aim of this study was to provide an overview of supplements in a sample of retail stores, with a focus on safety concerns. METHODS: Dermatology supplements were defined as those that featured the words "skin", "hair", "nails", "beauty", or "glow" in the product name or tagline. Seven stores including drug, grocery, department, and cosmetics stores were surveyed within a three-mile radius. Data were extracted from the Supplement Facts label of each product. RESULTS: A total of 176 separate supplements were identified, containing a total of 255 distinct ingredients. These included vitamins, minerals, food extracts, botanicals, animal products (collagen, fish oils), amino acids, a hormone, and distinct microbial strains. CONCLUSION: This survey of "dermatology" supplements available in local retailers raised several safety concerns, including potential interactions, teratogenicity risks, a lack of independent third-party testing, lack of warning labels, and nutrient "overdosing". Given limited regulation of dietary supplements, it is imperative that physicians educate patients on the potential risks. These include risks related to supplement ingredients and dosages, as well as risks related to the lack of regulatory oversight. Patients must also be educated about the multiple gaps in our knowledge of dietary supplements, especially in terms of efficacy and long-term safety.