GABAB receptors induce phasic release from medial habenula terminals through activity-dependent recruitment of release-ready vesicles.

GABAB receptor (GBR) activation inhibits neurotransmitter release in axon terminals in the brain, except in medial habenula (MHb) terminals, which show robust potentiation. However, mechanisms underlying this enigmatic potentiation remain elusive. Here, we report that GBR activation on MHb terminals induces an activity-dependent transition from a facilitating, tonic to a depressing, phasic neurotransmitter release mode. This transition is accompanied by a 4.1-fold increase in readily releasable vesicle pool (RRP) size and a 3.5-fold increase of docked synaptic vesicles (SVs) at the presynaptic active zone (AZ). Strikingly, the depressing phasic release exhibits looser coupling distance than the tonic release. Furthermore, the tonic and phasic release are selectively affected by deletion of synaptoporin (SPO) and Ca2+-dependent activator protein for secretion 2 (CAPS2), respectively. SPO modulates augmentation, the short-term plasticity associated with tonic release, and CAPS2 retains the increased RRP for initial responses in phasic response trains. The cytosolic protein CAPS2 showed a SV-associated distribution similar to the vesicular transmembrane protein SPO, and they were colocalized in the same terminals. We developed the "Flash and Freeze-fracture" method, and revealed the release of SPO-associated vesicles in both tonic and phasic modes and activity-dependent recruitment of CAPS2 to the AZ during phasic release, which lasted several minutes. Overall, these results indicate that GBR activation translocates CAPS2 to the AZ along with the fusion of CAPS2-associated SVs, contributing to persistency of the RRP increase. Thus, we identified structural and molecular mechanisms underlying tonic and phasic neurotransmitter release and their transition by GBR activation in MHb terminals.

Dense 4D nanoscale reconstruction of living brain tissue.

Three-dimensional (3D) reconstruction of living brain tissue down to an individual synapse level would create opportunities for decoding the dynamics and structure-function relationships of the brain's complex and dense information processing network; however, this has been hindered by insufficient 3D resolution, inadequate signal-to-noise ratio and prohibitive light burden in optical imaging, whereas electron microscopy is inherently static. Here we solved these challenges by developing an integrated optical/machine-learning technology, LIONESS (live information-optimized nanoscopy enabling saturated segmentation). This leverages optical modifications to stimulated emission depletion microscopy in comprehensively, extracellularly labeled tissue and previous information on sample structure via machine learning to simultaneously achieve isotropic super-resolution, high signal-to-noise ratio and compatibility with living tissue. This allows dense deep-learning-based instance segmentation and 3D reconstruction at a synapse level, incorporating molecular, activity and morphodynamic information. LIONESS opens up avenues for studying the dynamic functional (nano-)architecture of living brain tissue.

Maxillary sinus floor augmentation with autogenous bone graft compared with composite grafts: A one-year single-blinded randomized controlled trial.

OBJECTIVE: The objective was to assess the one year implant treatment outcome and patient-related outcome measures (PROMs) following maxillary sinus floor augmentation (MSFA) with autogenous bone graft (ABG) from the zygomatic buttress (control) compared with 1:1 mixture of ABG and anorganic porcine bone mineral (APBM) (Test I) or biphasic bone graft material (BBGM) (Test II). MATERIALS AND METHODS: Sixty healthy patients (34 females, 26 males) were randomly allocated to either control or test groups. Outcome measures included survival of suprastructures and implants, implant stability quotient, health status of peri-implant tissue, peri-implant marginal bone loss, frequency of complications, and PROMs using Oral Health Impact Profile-14 combined with questionnaire assessing patient perception of peri-implant soft tissue, prosthetic solution, implant function, and implant treatment outcome using visual analogue scale. Mean differences were expressed with standard deviation and 95% confidence interval. Level of significance was .05. RESULTS: All suprastructures and implants were well-functioning after one year of functional implant loading. There was no significant difference between control and test groups in any of the applied outcome measures. The implant stability significantly increased from implant placement to abutment connection within all groups (p < .001). High patient satisfaction and significant improvement in oral health-related quality of life was also reported within all groups. CONCLUSION: This study demonstrates that MSFA with composite grafts containing minimal amounts of ABG reveals comparable implant treatment outcomes as compared with ABG alone, after one year of functional implant loading. Extensive ABG harvesting in conjunction with MSFA therefore seems not to be needed.

Endoscopic vacuum therapy (eVAC) combined with continuous perianastomotic irrigation for prevention of anastomotic leak after surgical ampullectomy.

PURPOSE: Transduodenal surgical ampullectomy (tAMP) with papillary reimplantation is a valid alternative to pancreaticoduodenectomy for lesions of the periampullary region not amenable to endoscopic resection. As tAMP is burdened by high rates of biliopancreatic-enteric anastomotic leak, we tested preventive endoluminal vacuum therapy (eVAC) combined with post-operative continuous perianastomotic irrigation (CPI) to reduce such anastomotic leak. METHODS: Between 10/2013 and 09/2023, 37 patients undergoing laparotomic tAMP (with or without jejunal transposition) and papillary reimplantation at Hirslanden Klinik Zurich were retrospectively analysed; of these, 16 received prophylactic eVAC combined with CPI, while the remaining represented the historical cohort. RESULTS: The eVAC-CPI-group and the historical-cohort were homogeneous in demographic characteristics. Surgery in the prophylactic eVAC-CPI-group lasted about 30 min longer due to eVAC application (p = 0.008). The biliopancreatico-enteric anastomotic leak rates were 6.2% in the eVAC-CIP-group vs. 19.0% in the historical-cohort (p = 0.266). Along, a strong trend of less severe post-operative complications in general (p = 0.073), and borderline-significantly less cases of acute pancreatitis (p = 0.057) and tAMP-related re-operations or re-interventions (p = 0.057) in particular, were observed in the eVAC-CPI-group. The only anastomotic leak in the eVAC-CPI-group was successfully managed through repeated cycles of eVAC. The device was well tolerated by all patients; no vacuum/irrigation-related complications or malfunctioning occurred. CONCLUSION: Our study is the first to provide some technical insights demonstrating the safety and feasibility of a prophylactic approach with eVAC and perianastomotic irrigation to reduce anastomotic leak after tAMP. Increasing the number of subjects will confirm the benefit of our promising results.

Lung Transplantation for Primary Ciliary Dyskinesia and Kartagener Syndrome: A Multicenter Study.

Primary ciliary dyskinesia, with or without situs abnormalities, is a rare lung disease that can lead to an irreversible lung damage that may progress to respiratory failure. Lung transplant can be considered in end-stage disease. This study describes the outcomes of the largest lung transplant population for PCD and for PCD with situs abnormalities, also identified as Kartagener's syndrome. Retrospectively collected data of 36 patients who underwent lung transplantation for PCD from 1995 to 2020 with or without SA as part of the European Society of Thoracic Surgeons Lung Transplantation Working Group on rare diseases. Primary outcomes of interest included survival and freedom from chronic lung allograft dysfunction. Secondary outcomes included primary graft dysfunction within 72 h and the rate of rejection ≥A2 within the first year. Among PCD recipients with and without SA, the mean overall and CLAD-free survival were 5.9 and 5.2 years with no significant differences between groups in terms of time to CLAD (HR: 0.92, 95% CI: 0.27-3.14, p = 0.894) or mortality (HR: 0.45, 95% CI: 0.14-1.43, p = 0.178). Postoperative rates of PGD were comparable between groups; rejection grades ≥A2 on first biopsy or within the first year was more common in patients with SA. This study provides a valuable insight on international practices of lung transplantation in patients with PCD. Lung transplantation is an acceptable treatment option in this population.

Impact of salivary contamination during implant placement with different surface characteristics in native and augmented bone: An in vivo study in sheep calvaria model.

OBJECTIVES: The aim of this study was to evaluate whether salivary contamination during placement of implants with different surface characteristics affects osseointegration in native and in augmented bone areas. MATERIALS AND METHODS: Forty eight implants with machined surface (MS) and 48 implants with moderately rough surface (RS) were tested in the calvaria of 12 sheep. At the first surgery, 64 bony critical defects were randomly created and were subsequently augmented with two materials (autogenous or bovine bone). After 5 weeks of graft healing, 8 implants were placed per sheep, in native bone and in the centre of the augmented defects. Forty eight implants were soaked with saliva before placement (contaminated group [CG]), while 48 implants were not (non-contaminated group [NCG]). Five weeks after implant placement, bone-to-implant contact (BIC) and bone material area fraction occupancy (BMAFO) were calculated histomorphometrically. RESULTS: Saliva contamination showed a significant negative effect (p = .000) on BIC, especially in augmented areas. RS showed significant positive effect on BIC, compared to MS (p = .000), while there were no significant differences for different bone conditions (p = .103). For BMAFO, the contamination showed a significantly negative affect (p = .000), while there were no significant differences for surface characteristics (p = .322) and for bone condition (p = .538). CONCLUSION: Saliva contamination during dental implant placement has a negative effect on osseointegration in augmented areas. Moderately rough surface has a possible advantage in the aspect of initial bone to implant contact. However, it seems to be advisable to avoid saliva contamination especially for implants placed in augmented bone areas.

Integrated Mental Healthcare and Vocational Rehabilitation for People on Sick Leave with Anxiety or Depression: 24-Month Follow-up of the Randomized IBBIS Trial.

Integration of vocational rehabilitation and mental healthcare has shown some effect on work participation at 1-year follow-up after sick leave with depression and anxiety. We aimed to study the effect on work and health outcomes at 2-year follow-up, why we performed a randomized trial was conducted to study the effectiveness of integrated intervention (INT) compared to service as usual (SAU) and best practice mental healthcare (MHC). We included 631 participants, and at 24-month follow-up, we detected no differences in effect between INT and SAU. Compared to MHC, INT showed faster return-to-work (RTW) rates (p = 0.044) and a higher number of weeks in work (p = 0.024). No symptom differences were observed between the groups at 24 months. In conclusion, compared to SAU, INT was associated with a slightly higher work rate reaching borderline statistical significance at 12-month follow-up and lower stress levels at 6-month follow-up. The disappearance of relative effect between 12 and 24 months may be explained by the fact that the intervention lasted less than 12 months or by delayed spontaneous remission in the SAU group after 12 months. Despite the lack of effect at long-term follow-up, INT still performed slightly better than SAU overall. Moderate implementation difficulties, may partly explain the absence of the hypothesized effect. Integrated intervention, as implemented in this trial, showed some positive effects on mid-term vocational status and short-term stress symptom levels. However, these effects were not sustained beyond the duration of the intervention.

A cross-sectional national study of burnout and psychosocial work environment in vascular surgery in Denmark.

OBJECTIVE: Little is known about burnout among European vascular surgeons (VSs). In this study, the prevalence of burnout and its associated risk factors were investigated among all VSs and vascular surgeons in training (VSTs) in Denmark. METHODS: An anonymous electronic survey was distributed to all clinical active VSs and VSTs on January 1, 2020. Validated assessment tools were used to measure burnout and aspects of the psychosocial work environment. RESULTS: A total of 104 VSs and VSTs were invited to participate, and 82% (n = 85) completed the survey. The majority of the respondents were male (60%; n = 50) and VSs (67%; n = 61). Of the respondents, 82% (n = 70) reported either light (54%; n = 46), moderate (22%; n = 19), or severe (6%; n = 5) personal burnout. More than 50% (n = 47) reported work-related burnout, light (39%; n = 33), moderate (9%; n = 8), and severe (7%; n = 6), respectively, whereas 35% (n = 30) reported patient-related burnout, light (31%; n = 26), moderate (2%; n = 2), and severe (2%; n = 2), respectively. Respondents with more than four 24-hour on-call shifts per month had significantly higher work-related burnout scores, whereas respondents with home-living children and those aged 45 to 59 years showed significantly higher personal and patient-related burnout, respectively. There were strong associations between personal and work-related burnout and the psychosocial work environment, especially work organization and interpersonal relations, but not job demands. The prevalence of burnout was unevenly distributed across departments, with the most affected department having a burnout occurrence twice the least affected department. CONCLUSIONS: Based on a national survey conducted among all clinical active VSs and VSTs in Denmark, more than 80% (n = 70) suffered from burnout, of whom 28% (n = 24) suffered from moderate to severe personal burnout. The strong association with the psychosocial work environment, and the significant differences between departments, suggest that burnout is modifiable through changes in the work environment.

Simulation-Based Education of Endovascular Scrub Nurses Reduces Stress and Improves Team Performance.

INTRODUCTION: Endovascular procedures have become commonplace in vascular surgery. This development calls for new training strategies for future specialists. Most simulation-based education (SBE) programs have a monodisciplinary focus on physicians, although successful surgery is a multidisciplinary team effort. Mental stress impairs the learning process and surgical performance and heart rate variability (HRV) can be measured as a proxy for both mental and physical stress. This study aims to assess how SBE of endovascular scrub nurses affects team performance and HRV during endovascular aneurysm repair (EVAR). MATERIALS AND METHODS: Prospective interventional study in which EVAR-inexperienced scrub nurses followed a focused SBE EVAR program. During real-life EVAR procedures, HRV was continuously recorded with a wireless electrocardiogram patch and multidisciplinary team performance was assessed with the Imperial College Error CAPture (ICECAP) tool, before and after the SBE program, allowing each scrub nurse to serve as their own control. Eight scrub nurses with experience in lower limb endovascular procedures, but not EVAR, were invited to participate. RESULTS: Seven participants completed the study. In five of seven scrub nurses, HRV-derived stress levels during real-time EVAR procedures were lower after SBE compared to before SBE. Mean HRV increased from 24 msec to 35 msec (P < 0.001), indicating stress level reduction. Before SBE, the mean number of errors/hour was 7.3 (standard deviation ± 1.8) compared to 3.6 (standard deviation ± 2.7) after SBE. Most errors were categorized as technical (58 %) and communicative (23 %). CONCLUSIONS: SBE of scrub nurses may improve team performance and may lower mental stress during EVAR procedures. In this small study, we suggest using mental stress, as evaluated with HRV, and multidisciplinary team performance, as evaluated with ICECAP, to assess SBE effectiveness in real-case EVAR procedures. This SBE program and live ICECAP observations and electrocardiogram patches was well-accepted by scrub nurses and the entire team.

Recipient Comorbidities for Prediction of Primary Graft Dysfunction, Chronic Allograft Dysfunction and Survival After Lung Transplantation.

Since candidates with comorbidities are increasingly referred for lung transplantation, knowledge about comorbidities and their cumulative effect on outcomes is scarce. We retrospectively collected pretransplant comorbidities of all 513 adult recipients transplanted at our center between 1992-2019. Multiple logistic- and Cox regression models, adjusted for donor-, pre- and peri-operative variables, were used to detect independent risk factors for primary graft dysfunction grade-3 at 72 h (PGD3-T72), onset of chronic allograft dysfunction grade-3 (CLAD-3) and survival. An increasing comorbidity burden measured by Charleston-Deyo-Index was a multivariable risk for survival and PGD3-T72, but not for CLAD-3. Among comorbidities, congestive right heart failure or a mean pulmonary artery pressure >25 mmHg were independent risk factors for PGD3-T72 and survival, and a borderline risk for CLAD-3. Left heart failure, chronic atrial fibrillation, arterial hypertension, moderate liver disease, peptic ulcer disease, gastroesophageal reflux, diabetes with end organ damage, moderate to severe renal disease, osteoporosis, and diverticulosis were also independent risk factors for survival. For PGD3-T72, a BMI>30 kg/m2 was an additional independent risk. Epilepsy and a smoking history of the recipient of >20packyears are additional independent risk factors for CLAD-3. The comorbidity profile should therefore be closely considered for further clinical decision making in candidate selection.

Transcutaneous blood gas monitoring and tissue perfusion during common femoral thromboendarterectomy.

BACKGROUND: Improving tissue perfusion can improve clinical outcomes in surgical patients, where monitoring may aid clinicians in detecting adverse conditions and guide interventions. Transcutaneous monitoring (TCM) of oxygen (tcpO2) and carbon dioxide (tcpCO2) is a well-proven technology and could potentially serve as a measure of local circulation, perfusion and metabolism, but the clinical use is not thoroughly explored. The purpose of this proof-of-concept study was to investigate whether TCM of blood gasses could detect changes in perfusion during major vascular surgery. METHODS: Ten patients with peripheral arterial disease scheduled for lower limb major arterial revascularization under general anaesthesia were consecutively included. TcpO2 and tcpCO2 were continuously recorded from anaesthesia induction until skin closure with a TCM monitor placed on both legs and the thorax. Peripheral oxygen saturation was kept ≥94% and mean arterial blood pressure ≥65 mmHg. The primary outcomes were changes in tcpO2 and tcpCO2 related to arterial clamping and declamping during the procedure and analyzed by paired statistics. RESULTS: Femoral artery clamping resulted in a significant decrease in tcpO2 (-2.1 kPa, IQR-4.2; -0.8), p=.017)), followed by a significant increase in response to arterial declamping (5.5 kPa, IQR 0-7.3), p=.017)). Arterial clamping resulted in a statistically significant increase in tcpCO2 (0.9 kPa, IQR 0.3-5.4), p=.008)) and a significant decrease following declamping (-0.7 kPa, IQR -2.6; -0.2), p=.011)). CONCLUSION: Transcutaneous monitoring of oxygen and carbon dioxide is a feasible method for detection of extreme changes in tissue perfusion during arterial clamping and declamping, and its use for improving patient outcomes should be explored. Clinical Trials identifier: NCT04040478. Registered on July 31, 2019.

Adherence to instruction for use after endovascular repair of popliteal artery aneurysm.

OBJECTIVES: Endovascular repair (ER) of popliteal artery aneurysm (PAA) is an alternative to open repair. However, there is no standardized protocol for when to opt for ER and the decision is therefore at the discretion of the clinician. This study aims to evaluate the adherence to the Instruction For Use (IFU) in patients undergoing ER for PAA and factors associated with stent graft patency at one year. METHODS: The adherence to IFU provided by the manufacturer in 55 patients treated with Gore Viabahn® Endoprosthesis with Heparin Bioactive Surface for PAA between 2009 and 2019 were retrospectively analyzed. Duplex follow-up was performed at 30 days and one year. RESULTS: The two groups of patients treated within (n = 10) and not within (n = 45) IFU did not differ in patient demographics, diagnostic assessment, treatment or outcome. Forty-five patients (81.8%) received stent graft placement with at least one deviation according to IFU. Distal oversizing >20% was the most frequent deviation against IFU (n = 22, 40.0%). Primary patency at one year was 72%. Diameter size difference >1 mm between overlapping stent grafts (6/14 [43%], p = 0.013) and renal insufficiency (5/12 [42%], p = 0.0086) were associated with lower primary patency at one year. Age-adjusted analysis of tortuosity index (HR 1.78/SD, 95% CI 1.17-2.71; p = 0.0071) and maximal PAA angle (HR 1.73/SD, 95% CI 1.018-2.95; p = 0.043) were associated with major amputation/mortality at end of follow-up. CONCLUSION: The majority of patients undergoing ER for PAA were not treated within IFU. Diameter size difference >1 mm between overlapping stent grafts was associated with a higher loss of primary patency at one year. Multi-center studies with larger sample size and long-term follow up of patency are warranted.

Acute complications in the post-anaesthesia care unit after infrainguinal surgery for lower limb ischaemia - a prospective observational cohort study.

BACKGROUND: Arterial surgery for lower limb ischaemia is a frequently performed procedure in patients with severe cardio-pulmonary comorbidities, making them high-risk patients for acute postoperative complications with a need for prolonged stay in the post-anaesthesia care unit (PACU). However, detailed information on complications during the PACU stay is limited, hindering mechanism-based interventions for early enhanced recovery. Thus, we aimed to systematically describe acute complications and related risk factors in the immediate postoperative phase after infrainguinal arterial surgery. PATIENTS AND METHODS: Patients transferred to the PACU after infrainguinal arterial surgery due to chronic or acute lower limb ischaemia were consecutively included in a six-month observational cohort study. Pre- and intraoperative data included comorbidities as well as surgical and anaesthetic technique. Data on complications and treatments in the PACU were collected every 15 minutes using a standardised assessment tool. The primary endpoint was occurrence of predefined moderate or severe complications occurring during PACU stay. RESULTS: In total, 155 patients were included for analysis. Eighty (52 %) patients experienced episodes with oxygen desaturation (< 85 %) and moderate or severe pain occurred in 72 patients (47 %); however, circulatory complications (hypotension, tachycardia) were rare. Preoperative opioid use was a significant risk factor for moderate or severe pain in PACU (59 vs. 38 % chronic vs. opioid naïve patients (P = 0.01). CONCLUSIONS: Complications in the PACU after infrainguinal arterial surgery relates to saturation and pain, suggesting that future efforts should focus on anaesthesia and analgesic techniques including opioid sparing regimes to enhance early postoperative recovery.

The Phosphorylation State of the Drosophila TRP Channel Modulates the Frequency Response to Oscillating Light In Vivo.

Drosophila photoreceptors respond to oscillating light of high frequency (∼100 Hz), while the detected maximal frequency is modulated by the light rearing conditions, thus enabling high sensitivity to light and high temporal resolution. However, the molecular basis for this adaptive process is unclear. Here, we report that dephosphorylation of the light-activated transient receptor potential (TRP) ion channel at S936 is a fast, graded, light-dependent, and Ca2+-dependent process that is partially modulated by the rhodopsin phosphatase retinal degeneration C (RDGC). Electroretinogram measurements of the frequency response to oscillating lights in vivo revealed that dark-reared flies expressing wild-type TRP exhibited a detection limit of oscillating light at relatively low frequencies, which was shifted to higher frequencies upon light adaptation. Strikingly, preventing phosphorylation of the S936-TRP site by alanine substitution in transgenic Drosophila (trpS936A ) abolished the difference in frequency response between dark-adapted and light-adapted flies, resulting in high-frequency response also in dark-adapted flies. In contrast, inserting a phosphomimetic mutation by substituting the S936-TRP site to aspartic acid (trpS936D ) set the frequency response of light-adapted flies to low frequencies typical of dark-adapted flies. Light-adapted rdgC mutant flies showed relatively high S936-TRP phosphorylation levels and light-dark phosphorylation dynamics. These findings suggest that RDGC is one but not the only phosphatase involved in pS936-TRP dephosphorylation. Together, this study indicates that TRP channel dephosphorylation is a regulatory process that affects the detection limit of oscillating light according to the light rearing condition, thus adjusting dynamic processing of visual information under varying light conditions.SIGNIFICANCE STATEMENTDrosophila photoreceptors exhibit high temporal resolution as manifested in frequency response to oscillating light of high frequency (≤∼100 Hz). Light rearing conditions modulate the maximal frequency detected by photoreceptors, thus enabling them to maintain high sensitivity to light and high temporal resolution. However, the precise mechanisms for this process are not fully understood. Here, we show by combination of biochemistry and in vivo electrophysiology that transient receptor potential (TRP) channel dephosphorylation at a specific site is a fast, light-activated and Ca2+-dependent regulatory process. TRP dephosphorylation affects the detection limit of oscillating light according to the adaptation state of the photoreceptor cells by shifting the detection limit to higher frequencies upon light adaptation. This novel mechanism thus adjusts dynamic processing of visual information under varying light conditions.

Strength and duration of perisomatic GABAergic inhibition depend on distance between synaptically connected cells.

GABAergic perisoma-inhibiting fast-spiking interneurons (PIIs) effectively control the activity of large neuron populations by their wide axonal arborizations. It is generally assumed that the output of one PII to its target cells is strong and rapid. Here, we show that, unexpectedly, both strength and time course of PII-mediated perisomatic inhibition change with distance between synaptically connected partners in the rodent hippocampus. Synaptic signals become weaker due to lower contact numbers and decay more slowly with distance, very likely resulting from changes in GABAA receptor subunit composition. When distance-dependent synaptic inhibition is introduced to a rhythmically active neuronal network model, randomly driven principal cell assemblies are strongly synchronized by the PIIs, leading to higher precision in principal cell spike times than in a network with uniform synaptic inhibition.

Maxillary Sinus Floor Augmentation With Synthetic Bone Substitutes Compared With Other Grafting Materials: A Systematic Review and Meta-analysis.

OBJECTIVE: To test the hypotheses of no differences in implant treatment outcome after maxillary sinus floor augmentation (MSFA) with synthetic bone substitutes (SBS) compared with other grafting materials applying the lateral window technique. MATERIALS AND METHODS: A MEDLINE/PubMed, Embase and Cochrane Library search in combination with hand-search of selected journals was conducted. RESULTS: Five randomized controlled trials with low risk of bias fulfilled the inclusion criteria. SBS disclosed high survival rate of suprastructures and implants with no significant differences compared to autogenous bone graft or xenograft. Meta-analysis revealed a patient-based implant survival rate of 0.98 (confidence interval: 0.89-1.08), indicating no differences between SBS and xenograft. SBS demonstrated significant less newly formed bone compared with autogenous bone graft, whereas no significant difference was revealed as compared to xenograft. High implant stability values, limited periimplant marginal bone loss, and few complications were reported with SBS. CONCLUSIONS: There seem to be no differences in implant treatment outcome after MSFA with SBS compared to other grafting materials.

Intrinsic membrane properties determine hippocampal differential firing pattern in vivo in anesthetized rats.

The hippocampus plays a key role in learning and memory. Previous studies suggested that the main types of principal neurons, dentate gyrus granule cells (GCs), CA3 pyramidal neurons, and CA1 pyramidal neurons, differ in their activity pattern, with sparse firing in GCs and more frequent firing in CA3 and CA1 pyramidal neurons. It has been assumed but never shown that such different activity may be caused by differential synaptic excitation. To test this hypothesis, we performed high-resolution whole-cell patch-clamp recordings in anesthetized rats in vivo. In contrast to previous in vitro data, both CA3 and CA1 pyramidal neurons fired action potentials spontaneously, with a frequency of ∼3-6 Hz, whereas GCs were silent. Furthermore, both CA3 and CA1 cells primarily fired in bursts. To determine the underlying mechanisms, we quantitatively assessed the frequency of spontaneous excitatory synaptic input, the passive membrane properties, and the active membrane characteristics. Surprisingly, GCs showed comparable synaptic excitation to CA3 and CA1 cells and the highest ratio of excitation versus hyperpolarizing inhibition. Thus, differential synaptic excitation is not responsible for differences in firing. Moreover, the three types of hippocampal neurons markedly differed in their passive properties. While GCs showed the most negative membrane potential, CA3 pyramidal neurons had the highest input resistance and the slowest membrane time constant. The three types of neurons also differed in the active membrane characteristics. GCs showed the highest action potential threshold, but displayed the largest gain of the input-output curves. In conclusion, our results reveal that differential firing of the three main types of hippocampal principal neurons in vivo is not primarily caused by differences in the characteristics of the synaptic input, but by the distinct properties of synaptic integration and input-output transformation.

Nanodomain coupling between Ca²âº channels and sensors of exocytosis at fast mammalian synapses.

The physical distance between presynaptic Ca(2+) channels and the Ca(2+) sensors that trigger exocytosis of neurotransmitter-containing vesicles is a key determinant of the signalling properties of synapses in the nervous system. Recent functional analysis indicates that in some fast central synapses, transmitter release is triggered by a small number of Ca(2+) channels that are coupled to Ca(2+) sensors at the nanometre scale. Molecular analysis suggests that this tight coupling is generated by protein-protein interactions involving Ca(2+) channels, Ca(2+) sensors and various other synaptic proteins. Nanodomain coupling has several functional advantages, as it increases the efficacy, speed and energy efficiency of synaptic transmission.

Morpho-physiological criteria divide dentate gyrus interneurons into classes.

GABAergic inhibitory interneurons control fundamental aspects of neuronal network function. Their functional roles are assumed to be defined by the identity of their input synapses, the architecture of their dendritic tree, the passive and active membrane properties and finally the nature of their postsynaptic targets. Indeed, interneurons display a high degree of morphological and physiological heterogeneity. However, whether their morphological and physiological characteristics are correlated and whether interneuron diversity can be described by a continuum of GABAergic cell types or by distinct classes has remained unclear. Here we perform a detailed morphological and physiological characterization of GABAergic cells in the dentate gyrus, the input region of the hippocampus. To achieve an unbiased and efficient sampling and classification we used knock-in mice expressing the enhanced green fluorescent protein (eGFP) in glutamate decarboxylase 67 (GAD67)-positive neurons and performed cluster analysis. We identified five interneuron classes, each of them characterized by a distinct set of anatomical and physiological parameters. Cross-correlation analysis further revealed a direct relation between morphological and physiological properties indicating that dentate gyrus interneurons fall into functionally distinct classes which may differentially control neuronal network activity.