Implanted Pulse Generators in Lower Extremity Neuroprostheses: A 25-Year Review.

OBJECTIVES: Neuroprosthetic devices can improve quality of life by providing an alternative option for motor function lost after spinal cord injury, stroke, and other central nervous system disorders. The objective of this study is to analyze the outcomes of implanted pulse generators that our research group installed in volunteers with paralysis to assist with lower extremity function over a 25-year period, specifically, to determine survival rates and common modes of malfunction, reasons for removal or revision, and precipitating factors or external events that may have adversely influenced device performance. MATERIALS AND METHODS: Our implantable receiver-stimulator (IRS-8) and implantable stimulator-telemeter (IST-12 and IST-16) device histories were retrospectively reviewed through surgical notes, regulatory documentation, and manufacturing records from 1996 to 2021. RESULTS: Most of the 65 devices (64.6%) implanted in 43 volunteers remain implanted and operational. Seven underwent explantation owing to infection; seven had internal failures, and six were physically broken by external events. Of the 22 devices explanted, 15 were successfully replaced to restore recipients' enhanced functionality. There were no instances of sepsis or major health complications. The five infections that followed all 93 IRS and IST lower extremity research surgeries during this period indicate a pooled infection rate of 5.4%. The Kaplan-Meier analysis of technical malfunctions between the implant date and most recent follow-up shows five-, ten-, and 20-year device survival rates of 92%, 84%, and 71%, respectively. CONCLUSIONS: Incidence of malfunction is similar to, whereas infection rates are slightly higher than, other commonly implanted medical devices. Future investigations will focus on infection prevention, modifying techniques on the basis of recipient demographics, lifestyle factors, and education, and integrating similar experience of motor neuroprostheses used in other applications.

Predictive factors of graft detachment and rebubbling after descemet membrane endothelial keratoplasty.

PURPOSE: To identify risk and predictive factors associated with the need of rebubbling in the eye of patients who underwent a descemet membrane endothelial keratoplasty (DMEK). METHODS: The records of patients who underwent DMEK were retrospectively analyzed. Data regarding comorbidities, intraoperative characteristics, and postoperative treatments or complications were collected. The central corneal thickness (CCT) was measured by optical coherence tomography before and the day after DMEK. Univariate and multivariate analyses were performed. RESULTS: Of the 333 DMEK, rebubbling was performed in 119 cases (36%). Preoperative subepithelial fibrosis and a history of penetrating keratoplasty (PK) were associated with significantly more graft detachment [OR of 3.55 (2.02-6.32; P < 0.001) and 5.89 (2.00-21.86; P = 0.003), respectively]. A decreased CCT the day after surgery reduced by 5.7-fold the risk of rebubbling (sensitivity/specificity of 0.42/0.93). Conversely, a 20% increase in the CCT the day after surgery increased by 4.5-fold the risk of rebubbling (sensitivity/specificity of 0.42/0.91). CONCLUSION: Variation of the CCT could be used as a predictive factor of rebubbling after DMEK. Patients with a 20% increase of CCT the day after surgery are at higher risk of graft detachment. Conversely, a reduced CCT the day after the surgery is associated with a reduced risk of rebubbling. Subepithelial fibrosis and history of PK were also identified as risk factors for rebubbling. Those predictive factors may help develop a customized approach for patients undergoing DMEK surgery.

Antifungal Properties, Abiotic Stress Resistance, and Biocontrol Ability of Bacillus mojavensis PS17.

Plant-protecting Bacillus sp. strains used as biocontrol agents frequently produce metabolites inhibiting phytopathogenic fungi. Recently, the search for a novel biocontrol agent with a wide spectrum of disease control drew attention to Bacillus subtilis and their related species, including Bacillus mojavensis. In this study, we determined the antifungal properties of the endophytic B. mojavensis PS17 isolated from wheat seeds. Metabolites produced by B. mojavensis PS-17 inhibit the growth of Fusarium graminearum, Fusarium oxysporum, Fusarium chlamydosporum, Ascochyta pisi, Alternaria alternate, Sclerotinia sclerotiorum, Verticillium dahliaee, and Epicoccum nigrum strains. B. mojavensis strain PS17 produces several hydrolytic enzymes, such as chitinase, ß-glucanase, cellulase, lipase, and protease. Additionally, strain B. mojavensis PS17 demonstrates drought tolerance under osmotic pressure of -2.2 MPa and a moderate halotolerance in 5% (w/v) of NaCl. B. mojavensis PS17 on tomato seedlings was able to reduce lesions of Forl ZUM2407 by 48.11% ± 1.07, showing the potentials of B. mojavensis PS17 to be adapted as a biocontrol agent for agricultural use.

Altered brain-wide auditory networks in a zebrafish model of fragile X syndrome.

BACKGROUND: Loss or disrupted expression of the FMR1 gene causes fragile X syndrome (FXS), the most common monogenetic form of autism in humans. Although disruptions in sensory processing are core traits of FXS and autism, the neural underpinnings of these phenotypes are poorly understood. Using calcium imaging to record from the entire brain at cellular resolution, we investigated neuronal responses to visual and auditory stimuli in larval zebrafish, using fmr1 mutants to model FXS. The purpose of this study was to model the alterations of sensory networks, brain-wide and at cellular resolution, that underlie the sensory aspects of FXS and autism. RESULTS: Combining functional analyses with the neurons' anatomical positions, we found that fmr1-/- animals have normal responses to visual motion. However, there were several alterations in the auditory processing of fmr1-/- animals. Auditory responses were more plentiful in hindbrain structures and in the thalamus. The thalamus, torus semicircularis, and tegmentum had clusters of neurons that responded more strongly to auditory stimuli in fmr1-/- animals. Functional connectivity networks showed more inter-regional connectivity at lower sound intensities (a - 3 to - 6 dB shift) in fmr1-/- larvae compared to wild type. Finally, the decoding capacities of specific components of the ascending auditory pathway were altered: the octavolateralis nucleus within the hindbrain had significantly stronger decoding of auditory amplitude while the telencephalon had weaker decoding in fmr1-/- mutants. CONCLUSIONS: We demonstrated that fmr1-/- larvae are hypersensitive to sound, with a 3-6 dB shift in sensitivity, and identified four sub-cortical brain regions with more plentiful responses and/or greater response strengths to auditory stimuli. We also constructed an experimentally supported model of how auditory information may be processed brain-wide in fmr1-/- larvae. Our model suggests that the early ascending auditory pathway transmits more auditory information, with less filtering and modulation, in this model of FXS.

[Contribution of « GIGA-Cancer ¼ at ULiege to the research on tumour microenvironment]. / Apport du «GIGA-Cancer¼ de l'ULiège à la recherche sur le microenvironnement tumoral.

The evolution of cancers is dictated by the intrinsic characteristics of malignant cells, but also by the multiple dynamic and reciprocal interactions that they establish with their tissue and cellular environment. This tumour microenvironment is therefore the subject of an ever-increasing part of cancer researches. These notably shed light on the plasticity of function of these non-malignant cells and on the diversity of their impact on the progression of the disease, both in primary tumours and during the formation of metastases. The improvement of the current therapy and the development of innovative treatments therefore require the identification of these cell subpopulations, either «allies¼ or «enemies¼ of aggressive cancer cells, as well as a more extensive understanding of the mechanisms modulating their phenotypes. This article summarizes some research projects carried out in two GIGA-Cancer laboratories supported by «Télévie¼ and the «Fondation Léon Frédéricq¼.

L'évolution de la pathologie cancéreuse est dictée par les caractéristiques intrinsèques des cellules malignes, mais également par les multiples interactions dynamiques et réciproques qu'elles établissent avec leur environnement tissulaire et cellulaire. Ce microenvironnement tumoral est donc l'objet d'une part sans cesse croissante des recherches en cancérologie. Celles-ci ont, notamment, mis en lumière la plasticité de fonction de ces cellules non malignes et la diversité de leurs impacts sur l'évolution de la maladie, tant dans les tumeurs primaires que lors de la formation des métastases. L'amélioration des traitements actuels et la mise au point de traitements novateurs nécessiteront donc l'identification fine de ces sous-populations cellulaires «alliées¼ ou «ennemies¼ des cellules cancéreuses agressives, ainsi qu'une compréhension accrue des mécanismes modulant leurs phénotypes. Cet article résume quelques projets de recherche menés dans deux laboratoires du GIGA-Cancer, soutenus notamment par Télévie et la Fondation Léon Fredericq.

Chronic nerve health following implantation of femoral nerve cuff electrodes.

BACKGROUND: Peripheral nerve stimulation with implanted nerve cuff electrodes can restore standing, stepping and other functions to individuals with spinal cord injury (SCI). We performed the first study to evaluate the clinical electrodiagnostic changes due to electrode implantation acutely, chronic presence on the nerve peri- and post-operatively, and long-term delivery of electrical stimulation. METHODS: A man with bilateral lower extremity paralysis secondary to cervical SCI sustained 5 years prior to enrollment received an implanted standing neuroprosthesis including composite flat interface nerve electrodes (C-FINEs) electrodes implanted around the proximal femoral nerves near the inguinal ligaments. Electromyography quantified neurophysiology preoperatively, intraoperatively, and through 1 year postoperatively. Stimulation charge thresholds, evoked knee extension moments, and weight distribution during standing quantified neuroprosthesis function over the same interval. RESULTS: Femoral compound motor unit action potentials increased 31% in amplitude and 34% in area while evoked knee extension moments increased significantly (p < 0.01) by 79% over 1 year of rehabilitation with standing and quadriceps exercises. Charge thresholds were low and stable, averaging 19.7 nC ± 6.2 (SEM). Changes in saphenous nerve action potentials and needle electromyography suggested minor nerve irritation perioperatively. CONCLUSIONS: This is the first human trial reporting acute and chronic neurophysiologic changes due to application of and stimulation through nerve cuff electrodes. Electrodiagnostics indicated preserved nerve health with strengthened responses following stimulated exercise. Temporary electrodiagnostic changes suggest minor nerve irritation only intra- and peri-operatively, not continuing chronically nor impacting function. These outcomes follow implantation of a neuroprosthesis enabling standing and demonstrate the ability to safely implant electrodes on the proximal femoral nerve close to the inguinal ligament. We demonstrate the electrodiagnostic findings that can be expected from implanting nerve cuff electrodes and their time-course for resolution, potentially applicable to prostheses modulating other peripheral nerves and functions. TRIAL REGISTRATION: ClinicalTrials.gov NCT01923662 , retrospectively registered August 15, 2013.

Epithelial requirement for in vitro proliferation and xenograft growth and metastasis of MDA-MB-468 human breast cancer cells: oncogenic rather than tumor-suppressive role of E-cadherin.

BACKGROUND: Epithelial-to-mesenchymal transition (EMT) is associated with downregulated E-cadherin and frequently with decreased proliferation. Proliferation may be restored in secondary metastases by mesenchymal-to-epithelial transition (MET). We tested whether E-cadherin maintains epithelial proliferation in MDA-MB-468 breast cancer cells, facilitating metastatic colonization in severe combined immunodeficiency (SCID) mice. METHODS: EMT/MET markers were assessed in xenograft tumors by immunohistochemistry. Stable E-cadherin manipulation was effected by transfection and verified by Western blotting, immunocytochemistry, and quantitative polymerase chain reaction (qPCR). Effects of E-cadherin manipulation on proliferation and chemomigration were assessed in vitro by performing sulforhodamine B assays and Transwell assays, respectively. Invasion was assessed by Matrigel outgrowth; growth in vivo was assessed in SCID mice; and EMT status was assessed by qPCR. Hypoxic response of E-cadherin knockdown cell lines was assessed by qPCR after hypoxic culture. Repeated measures analysis of variance (ANOVA), one- and two-way ANOVA with posttests, and paired Student's t tests were performed to determine significance (p < 0.05). RESULTS: EMT occurred at the necrotic interface of MDA-MB-468 xenografts in regions of hypoxia. Extratumoral deposits (vascular and lymphatic inclusions, local and axillary nodes, and lung metastases) strongly expressed E-cadherin. MDA-MB-468 cells overexpressing E-cadherin were more proliferative and less migratory in vitro, whereas E-cadherin knockdown (short hairpin CDH1 [shCDH1]) cells were more migratory and invasive, less proliferative, and took longer to form tumors. shCDH1-MDA-MB-468 xenografts did not contain the hypoxia-induced necrotic areas observed in wild-type (WT) and shSCR-MDA-MB-468 tumors, but they did not exhibit an impaired hypoxic response in vitro. Although vimentin expression was not stimulated by E-cadherin knockdown in 2D or 3D cultures, xenografts of these cells were globally vimentin-positive rather than exhibiting regional EMT, and they expressed higher SNA1 than their in vitro counterparts. E-cadherin suppression caused a trend toward reduced lung metastasis, whereas E-cadherin overexpression resulted in the reverse trend, consistent with the increased proliferation rate and predominantly epithelial phenotype of MDA-MB-468 cells outside the primary xenograft. This was also originally observed in WT xenografts. Furthermore, we found that patients with breast cancer that expressed E-cadherin were more likely to have metastases. CONCLUSIONS: E-cadherin expression promotes growth of primary breast tumors and conceivably the formation of metastases, supporting a role for MET in metastasis. E-cadherin needs to be reevaluated as a tumor suppressor.

Ageism and caring attitudes among nurses in oncology.

BACKGROUND: Although the incidence of cancer increases with age, elderly patients are often excluded from clinical trials. In addition, elderly patients are frequently undertreated in comparison to younger patients. One explanation for these observations is age stigma (i.e. ageism). In this context, this study has two objectives: (1) to replicate the results of previous studies that reported differential support of medical treatment depending on the patient's age in a different healthcare provider population (nurses rather than physicians); and (2) to determine whether support for expensive immunotherapy, adjuvant chemotherapy, or breast reconstruction is linked to ageism among nurses. METHOD: The participants were 76 nurses who specialized in oncology. They received four clinical vignettes: one vignette about an immunotherapy with a high societal cost (age of patient: 40 vs. 70 years), and three vignettes about adjuvant chemotherapy and breast reconstruction (age of patient: 35, 55, or 75 years - age was the only difference). A questionnaire and a fluency task were used to assess the participants' vision of aging. RESULTS: Our analyses show that support for immunotherapy, breast reconstruction, and chemotherapy is lower for older patients than for younger patients. Moreover, nurses' vision of aging influences support for breast reconstruction: nurses with a negative view of age discriminated more between a 75-year-old patient and a 35-year-old patient (less encouragement for the older patient). CONCLUSION: These results highlight the need for nurses and other healthcare providers to receive specific training about ageism and its consequences.

[State of contraception in 2016]. / Etat de la contraception en 2016.

INTRODUCTION: The Pill and other forms of hormonal contraception, if taken correctly, are very effective and safe for millions of women, but since a few years, due to the debates and controversies about the third- and fourth-generation pills, other options have gained in popularity. OBJECTIVES: to provide a review of oestroprogestative contraception (OP), progesta-tive contraception, IUDs with a focus on their advantages and side-effects according to the specific needs of women. METHODS: literature review and lessons learned from clinical practice. RESULTS: The importance of family and individual history, the life-style and socio-economic conditions are critical factors for advising women on the 15 contraceptive choices available to them. The risk/benefit ratio of OP contraception needs a yearly follow-up. The progestative contraception is the preferred option for women who have contraindication for oestrogen, are older than forty, and/or have risk factors such as a history of venous thromboembolism, overweight and smoking. The IUD usually is well tolerated and causes few side effects. Among the other contraceptive methods, sterilization and diaphragms are briefly discussed. CONCLUSION: Among the many safe and effective contraceptive methods, it is important for general practitioners to know the advantages and the side effects of each method, as well as the specific conditions of the woman, to propose the best options available. In case of difficulties of follow up or adherence to daily uptake, in particular among adolescents, long-acting methods such as IDU or implants are preferable.

INTRODUCTION: Longtemps préférées des femmes, les pilules sont en recul en Belgique depuis les polémiques sur les pilules de 3e et 4e génération. Si le recours à la contraception orale a diminué, d'autres prat iques contraceptives se sont renforcées. OBJECTIFS: fournir une description détaillée des contraceptifs oestroprogestatifs (OP), des contraceptifs à base de progestatifs seuls et des dispositifs intra-utérins, en soulignant leur intérêt mais aussi les risques de leur utilisation. METHODE: revue de la littérature et expérience clinique. RESULTATS: l'importance des antécédents personnels, familiaux, et du style de vie est déterminante pour évaluer les indications des différentes méthodes. En ce qui concerne les contraceptifs OP, le rapport risque/bénéfice nécessite un suivi annuel. La contraception progestative est une option choisie par de nombreuses femmes, particulièrement celles qui ont plus de 40 ans, et/ou des facteurs de risque comme le tabac, le surpoids ou des antécédents de TEV. Le dispositif intra-utérin est généralement bien toléré comme méthode contraceptive car il présente peu d'effets secondaires ou de complications. Parmi les autres méthodes contraceptives, la stérilisation féminine et le diaphragme sont brièvement discutés. CONCLUSION: Parmi les nombreuses possibilités de choix contraceptifs, il est important de faire connaître les indications et contre-indications en tenant compte de la situation de la personne. En cas de difficulté de suivi et d'observance, en particulier chez les adolescentes, la prescription des méthodes à longue durée d'action est préférable.

A selective small molecule NOP (ORL-1 receptor) partial agonist for the treatment of anxiety.

Small molecule (1) has been identified as a selective partial agonist of Opioid Receptor Like-1 (ORL-1) with potential utility for the treatment of anxiety and other disorders. Nociceptin (orphanin FQ) is an endogenous peptide ligand that binds to ORL-1, however it does not bind the classical δ, µ and κ opioid receptors with high affinity. The synthesis of 1 involved using a molecular diversity approach, to rapidly advance a library of compounds for biological testing. A lead selective potent partial agonist (35-fold ORL-1/Mu) progressed to ORL-1 (NOP or OP4) proof of concept testing in advanced studies. The synthetic approach and biological data for the related chemical series will be presented.

Risk assessment of dimethylfumarate residues in dwellings following contamination by treated furniture.

Recently, numerous cases of dermatitis induced by dimethylfumarate (DMFu) have been reported in Europe. DMFu has been used to prevent mold development in various items, although it is not registered as a biocide. In France, from October 2008 to December 2009, more than 100 cases were reported. Despite a ban on articles containing DMFu and the removal of potentially contaminated products, some people were still suffering from dermatitis or other health problems. The French Agency for Food, Environmental and Occupational Health & Safety was mandated to assess whether the existence in the past of DMFu-contaminated items in dwellings could continue to pose a threat to the health of inhabitants. A risk assessment was performed based on the classical risk analysis approach for environmental contaminants. Hazard assessment of DMFu with regard to its sensitizing properties was performed, based on human case reports collected in France between January 2009 and February 2010. For around half of the 132 individual cases reported, the causal link to DMFu was considered at least probable. An Organisation for Economic Co-Operation and Development (OECD) local lymph node assay performed in a study on mice showed strong sensitizing potential for DMFu. Exposure was assessed by measuring DMFu in items sampled in preselected dwellings. These investigations demonstrated that DMFu exposure can persist after removal of the primary contaminated items. We therefore concluded that there was clearly a risk of skin reactions in patients previously sensitized to DMFu. Furthermore, the available data do not support the existence of significant health effects through the respiratory route.

Incidence and Outcomes of Eye Trauma Associated With Recreative Use of Nonpowder Toy Guns: A 12-Year Retrospective Study.

PURPOSE: Nonpowder toy guns (NPTGs) are responsible for many ocular traumas. This study aims to detail the outcomes of these injuries depending on the causative NPTG. DESIGN: Retrospective, observational case series. METHODS: Cases of NPTG-associated ocular trauma managed in a Parisian eye emergency department between August 1, 2010, and January 1, 2023, were reviewed. The date of trauma, causative NPTG, patient demographics, initial and follow-up eye examinations, any surgical procedure, and visual outcomes for each ocular trauma were analyzed. RESULTS: Over 12 years, NPTGs were responsible for 324 eye injuries and 980 visits. Patients were mostly male (77.5%), and mean age at trauma was 16.2 years. Foam bullets or foam dart blasters accounted for 54.9% of traumas and were mainly responsible for corneal injuries and hyphema (30.9% and 27%, respectively). BB guns and airsoft guns were frequently responsible for anterior segment lesions, as well as intravitreal hemorrhages (14.7%) and commotio retinae (21.1%). Paintball guns accounted for the largest proportion of posterior segment lesions (eg, intraretinal or subretinal hemorrhages leading to macular atrophy/contusion maculopathy), and one-third of casualties had undergone ocular surgery. Among all traumas, final visual acuity was lower than 20/200 in 6.5% of cases. Phthisis occurred in 8 cases: Two were related to foam bullets or foam dart blaster injuries (1 contusion and 1 rupture), 2 other cases followed a rupture due to BB guns/airsoft guns, 1 case occurred after a rupture related to a paintball gunshot, and 3 others were due to other types of compressed air guns (1 rupture, 1 intraocular foreign body, and 1 total retinal detachment). CONCLUSIONS: NPTG-related ocular trauma outcomes differ according to the causative toy. Paintball guns and BB guns/airsoft gun-related traumas were more likely to be associated with severe lesions, but an increasing number of ocular injuries related to the use of foam bullets or foam dart blasters are reported in younger and younger children. Public health policies should promote the use of protective eyewear.

Cystoid macular oedema after descemet membrane endothelial keratoplasty.

AIMS: To determine the incidence and risk factors of cystoid macular oedema (CMO) following descemet membrane endothelial keratoplasty (DMEK) with or without combined cataract surgery (triple-DMEK). METHODS: We reviewed the records of patients who underwent DMEK surgery alone or triple-DMEK performed at the Rothschild Foundation Hospital (Paris, France) between January 2019 and March 2020. Patients with pre-existing CMO observed on the preoperative macular optical coherence tomography (OCT) were excluded. Spectral-domain OCT was performed in patients with postoperative visual impairment. Data regarding comorbidities, intraoperative characteristics and postoperative treatments or complications were collected and analysed. Univariate and multivariate analyses were performed. RESULTS: Twenty three of 246 eyes (9.36%) developed clinically significant (cs)-CMO after DMEK. Triple-DMEK was not associated with a higher risk to develop CMO (12.2% in DMEK alone and 6.1% in triple-DMEK). Pseudophakic bullous keratopathy (PBK ; 39.1% vs 9%; OR=3.5 (1.0 to 11.8), p=0.045) and epiretinal membrane (ERM; 39.1% vs 7.7%; OR=10.5 (3.4 to 32.3), p<0.001) were more frequently observed in patients who developed CMO. The occurrence of hyphaema during surgery was statistically associated with postoperative CMO (13% vs 1.3%; OR=7.1 (1.0 to 48.8) p=0.045). Peroperative epithelial debridement was statistically associated with postoperative CMO (65.2% vs 33.2%, p=0.005), but only in univariate analysis. CONCLUSIONS: We identified a clinically significant CMO incidence of 9.35% after DMEK. Patients with a history of ERM, PBK and intraoperative hyphaema may be at risk of developing CMO after DMEK surgery and should be monitored.

Specificities of pediatric ocular emergencies before and during the COVID-19 era: A retrospective comparative study in an eye-related emergency department in Paris.

INTRODUCTION: Epidemiological data on the use of eye-related emergency services by children are limited. The objective of this study was to determine how COVID-19 affected the epidemiological trends of pediatric ocular emergencies. METHODS: We performed a retrospective chart review of children under the age of 18 years who visited our eye-related emergency department between March 17 and June 7, 2020 and between March 18 and June 9, 2019. This was a descriptive and comparative analysis of the two study periods based on the demographic characteristics of patients and the diagnosis reported by the ophthalmologist in the digital medical charts. One of the investigators performed a second reading of the files to homogenize the diagnosis classification based on the most frequently found items. RESULTS: In total, 754 children were seen in our eye-related emergency department during the 2020 study period versus 1399 in 2019, representing a 46% decrease. In 2019, the four main diagnoses were traumatic injury (30%), allergic conjunctivitis (15%), infectious conjunctivitis (12%), and chalazion/blepharitis (12%). In the 2020 study period there was a significant decrease in the proportion of patients presenting with traumatic injuries (p < 0.001), infectious conjunctivitis (p = 0.03), and chalazion/blepharitis (p < 0.001). Consultations for chalazion/blepharitis were the most affected by the pandemic, followed by traumatic injuries (-72% and -64%, respectively). The proportion of patients who required surgery after trauma was higher in 2020 than in 2019 (p < 0.01), but the absolute number of severe trauma cases remained stable. CONCLUSIONS: The COVID-19 pandemic was accompanied by a decrease in the overall use of a pediatric eye-related emergency services in Paris. Visits due to benign causes and ocular trauma also decreased, but visits for more severe pathologies were not affected. Longer-term epidemiological studies may confirm or refute a change in eye emergency department use habits.

Optopharmacological tools for precise spatiotemporal control of oxytocin signaling in the central nervous system and periphery.

Oxytocin is a neuropeptide critical for maternal physiology and social behavior, and is thought to be dysregulated in several neuropsychiatric disorders. Despite the biological and neurocognitive importance of oxytocin signaling, methods are lacking to activate oxytocin receptors with high spatiotemporal precision in the brain and peripheral mammalian tissues. Here we developed and validated caged analogs of oxytocin which are functionally inert until cage release is triggered by ultraviolet light. We examined how focal versus global oxytocin application affected oxytocin-driven Ca2+ wave propagation in mouse mammary tissue. We also validated the application of caged oxytocin in the hippocampus and auditory cortex with electrophysiological recordings in vitro, and demonstrated that oxytocin uncaging can accelerate the onset of mouse maternal behavior in vivo. Together, these results demonstrate that optopharmacological control of caged peptides is a robust tool with spatiotemporal precision for modulating neuropeptide signaling throughout the brain and body.

From calcium imaging to graph topology.

Systems neuroscience is facing an ever-growing mountain of data. Recent advances in protein engineering and microscopy have together led to a paradigm shift in neuroscience; using fluorescence, we can now image the activity of every neuron through the whole brain of behaving animals. Even in larger organisms, the number of neurons that we can record simultaneously is increasing exponentially with time. This increase in the dimensionality of the data is being met with an explosion of computational and mathematical methods, each using disparate terminology, distinct approaches, and diverse mathematical concepts. Here we collect, organize, and explain multiple data analysis techniques that have been, or could be, applied to whole-brain imaging, using larval zebrafish as an example model. We begin with methods such as linear regression that are designed to detect relations between two variables. Next, we progress through network science and applied topological methods, which focus on the patterns of relations among many variables. Finally, we highlight the potential of generative models that could provide testable hypotheses on wiring rules and network progression through time, or disease progression. While we use examples of imaging from larval zebrafish, these approaches are suitable for any population-scale neural network modeling, and indeed, to applications beyond systems neuroscience. Computational approaches from network science and applied topology are not limited to larval zebrafish, or even to systems neuroscience, and we therefore conclude with a discussion of how such methods can be applied to diverse problems across the biological sciences.