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During prolonged trains of presynaptic action potentials (APs), synaptic release reaches a stable level that reflects the speed of replenishment of the readily releasable pool (RRP). Determining the size and filling dynamics of vesicular pools upstream of the RRP has been hampered by a lack of precision of synaptic output measurements during trains. Using the recent technique of tracking vesicular release in single active zone synapses, we now developed a method that allows the sizes of the RRP and upstream pools to be followed in time. We find that the RRP is fed by a small-sized pool containing approximately one to four vesicles per docking site at rest. This upstream pool is significantly depleted by short AP trains, and reaches a steady, depleted state for trains of >10 APs. We conclude that a small, highly dynamic vesicular pool upstream of the RRP potently controls synaptic strength during sustained stimulation.

It is often assumed that only stably docked synaptic vesicles can fuse following presynaptic action potential stimulation. However, during action potential trains docking sites are increasingly depleted, raising the question of the source of synaptic vesicles during sustained release. We have recently developed methods to reliably measure release latencies during high frequency trains at single synapses between parallel fibers and molecular layer interneurons. The latency distribution exhibits a single fast component at train onset but contains both a fast and a slow component later in the train. The contribution of the slow component increases with stimulation frequency and with release probability and decreases when blocking the docking step with latrunculin. These results suggest that the slow component reflects sequential docking and release in immediate succession. The transition from fast to slow component, as well as a later transition to asynchronous release, appear as successive adaptations of the synapse to maintain fidelity at the expense of time accuracy. Traditionally, synaptic release latency has been viewed as constant. Here, at parallel fiber-interneuron  synapses, authors see that with sustained release emerges a slow component of increased latencies, which can be simulated with a 2-step model comprised of vesicle docking followed by release.

Recent research suggests that in central mammalian synapses, active zones contain several docking sites acting in parallel. Before release, one or several synaptic vesicles (SVs) are thought to bind to each docking site, forming the readily releasable pool (RRP). Determining the RRP size per docking site has important implications for short-term synaptic plasticity. Here, using mouse cerebellar slices, we take advantage of recently developed methods to count the number of released SVs at single glutamatergic synapses in response to trains of action potentials (APs). In each recording, the number of docking sites was determined by fitting with a binomial model the number of released SVs in response to individual APs. After normalization with respect to the number of docking sites, the summed number of released SVs following a train of APs was used to estimate of the RRP size per docking site. To improve this estimate, various steps were taken to maximize the release probability of docked SVs, the occupancy of docking sites, as well as the extent of synaptic depression. Under these conditions, the RRP size reached a maximum value close to two SVs per docking site. The results indicate that each docking site contains two distinct SV-binding sites that can simultaneously accommodate up to one SV each. They further suggest that under special experimental conditions, as both sites are close to full occupancy, a maximal RRP size of two SVs per docking site can be reached. More generally, the results validate a sequential two-step docking model previously proposed at this preparation.

The Hall effect can be extended by inducing a temperature gradient in lieu of electric field that is known as the Nernst (-Ettingshausen) effect. The recently discovered spin Nernst effect in heavy metals continues to enrich the picture of Nernst effect-related phenomena. However, the collection would not be complete without mentioning the valley degree of freedom benchmarked by the valley Hall effect. Here we show the experimental evidence of its missing counterpart, the valley Nernst effect. Using millimeter-sized WSe 2 mono-multi-layers and the ferromagnetic resonance-spin pumping technique, we are able to apply a temperature gradient by off-centering the sample in the radio frequency cavity and address a single valley through spin-valley coupling. The combination of a temperature gradient and the valley polarization leads to the valley Nernst effect in WSe 2 that we detect electrically at room temperature. The valley Nernst coefficient is in good agreement with the predicted value. Atomically thin transition metal dichalcogenides possess a valley degree of freedom, which could enrich the physics underpinning the conventional Nernst effect observed in traditional solids. Here, the authors report experimental evidence of the valley Nernst effect in WSe 2  at room temperature.

Many central synapses contain a single presynaptic active zone and a single postsynaptic density. Vesicular release statistics at such “simple synapses” indicate that they contain a small complement of docking sites where vesicles repetitively dock and fuse. In this work, we investigate functional and morphological aspects of docking sites at simple synapses made between cerebellar parallel fibers and molecular layer interneurons. Using immunogold labeling of SDS-treated freeze-fracture replicas, we find that Cav2.1 channels form several clusters per active zone with about nine channels per cluster. The mean value and range of intersynaptic variation are similar for Cav2.1 cluster numbers and for functional estimates of docking-site numbers obtained from the maximum numbers of released vesicles per action potential. Both numbers grow in relation with synaptic size and decrease by a similar extent with age between 2 wk and 4 wk postnatal. Thus, the mean docking-site numbers were 3.15 at 2 wk (range: 1–10) and 2.03 at 4 wk (range: 1–4), whereas the mean numbers of Cav2.1 clusters were 2.84 at 2 wk (range: 1–8) and 2.37 at 4 wk (range: 1–5). These changes were accompanied by decreases of miniature current amplitude (from 93 pA to 56 pA), active-zone surface area (from 0.0427 μm² to 0.0234 μm²), and initial success rate (from 0.609 to 0.353), indicating a tightening of synaptic transmission with development. Altogether, these results suggest a close correspondence between the number of functionally defined vesicular docking sites and that of clusters of voltage-gated calcium channels.

Even though it has been known for some time that in many mammalian brain areas interneurons are electrically coupled, a quantitative description of the network electrical connectivity and its impact on cellular passive properties is still lacking. Approaches used so far to solve this problem are limited because they do not readily distinguish junctions among direct neighbors from indirect junctions involving intermediary, multiply connected cells. In the cerebellar cortex, anatomical and functional evidence indicates electrical coupling between molecular layer interneurons (basket and stellate cells). An analysis of the capacitive currents obtained under voltage clamp in molecular layer interneurons of juvenile rats or mice reveals an exponential component with a time constant of ∼20 ms, which represents capacitive loading of neighboring cells through gap junctions. These results, taken together with dual cell recording of electrical synapses, have led us to estimate the number of direct neighbors to be ∼4 for rat basket cells and ∼1 for rat stellate cells. The weighted number of neighbors (number of neighbors, both direct and indirect, weighted with the percentage of voltage deflection at steady state) was 1.69 in basket cells and 0.23 in stellate cells. The last numbers indicate the spread of potential changes in the network and serve to estimate the contribution of gap junctions to cellular input conductance. In conclusion the present work offers effective tools to analyze the connectivity of electrically connected interneuron networks, and it indicates that in juvenile rodents, electrical communication is stronger among basket cells than among stellate cells.

A large electric field at the surface of a ferromagnetic metal is expected to appreciably change its electron density. In particular, the metal's intrinsic magnetic properties, which are commonly regarded as fixed material constants, will be affected. This requires, however, that the surface has a strong influence on the material's properties, as is the case with ultrathin films. We demonstrated that the magnetocrystalline anisotropy of ordered iron-platinum (FePt) and iron-palladium (FePd) intermetallic compounds can be reversibly modified by an applied electric field when immersed in an electrolyte. A voltage change of -0.6 volts on 2-nanometer-thick films altered the coercivity by -4.5 and +1% in FePt and FePd, respectively. The modification of the magnetic parameters was attributed to a change in the number of unpaired d electrons in response to the applied electric field. Our device structure is general and should be applicable for characterization of other thin-film magnetic systems.

Background The oleaginous yeast Yarrowia lipolytica is an organism of choice for the tailored production of various compounds such as biofuels or biopolymers. When properly engineered, it is capable of producing medium-chain-length polyhydroxyalkanoate (mcl-PHA), a biobased and biodegradable polymer that can be used as bioplastics or biopolymers for environmental and biomedical applications. Results This study describes the bioproduction and the main properties of two different mcl-PHA polymers. We generated by metabolic engineering, strains of Y . lipolytica capable of accumulating more than 25% (g/g) of mcl-PHA polymers. Depending of the strain genetic background and the culture conditions, we produced (i) a mcl-PHA homopolymer of 3-hydroxydodecanoic acids, with a mass-average molar mass (M w ) of 316,000 g/mol, showing soft thermoplastic properties with potential applications in packaging and (ii) a mcl-PHA copolymer made of 3-hydroxyoctanoic (3HO), decanoic (3HD), dodecanoic (3HDD) and tetradecanoic (3TD) acids with a M w of 128,000 g/mol, behaving like a thermoplastic elastomer with potential applications in biomedical material. Conclusion The ability to engineer Y. lipolytica to produce tailored PHAs together with the range of possible applications regarding their biophysical and mechanical properties opens new perspectives in the field of PHA bioproduction.

In recent years, two-dimensional van der Waals materials have emerged as an important platform for the observation of long-range ferromagnetic order in atomically thin layers. Although heterostructures of such materials can be conceived to harness and couple a wide range of magneto-optical and magneto-electrical properties, technologically relevant applications require Curie temperatures at or above room temperature and the ability to grow films over large areas. Here we demonstrate the large-area growth of single-crystal ultrathin films of stoichiometric Fe5GeTe2 on an insulating substrate using molecular beam epitaxy. Magnetic measurements show the persistence of soft ferromagnetism up to room temperature in 12 nm-thick films, with a Curie temperature of 293 K, and a weak out-of-plane magnetocrystalline anisotropy. The ferromagnetic order is preserved in bilayer Fe5GeTe2, with Curie temperature decreasing to 229 K. Surface, chemical, and structural characterizations confirm the layer-by-layer growth, 5:1:2 Fe:Ge:Te stoichiometric elementary composition, and single-crystalline character of the films.

Central mammalian synapses release synaptic vesicles in dedicated structures called docking/release sites. It has been assumed that when voltage-dependent calcium entry is sufficiently large, synaptic output attains a maximum value of one synaptic vesicle per action potential and per site. Here we use deconvolution to count synaptic vesicle output at single sites (mean site number per synapse: 3.6). When increasing calcium entry with tetraethylammonium in 1.5 mM external calcium concentration, we find that synaptic output saturates at 0.22 vesicle per site, not at 1 vesicle per site. Fitting the results with current models of calcium-dependent exocytosis indicates that the 0.22 vesicle limit reflects the probability of docking sites to be occupied by synaptic vesicles at rest, as only docked vesicles can be released. With 3 mM external calcium, the maximum output per site increases to 0.47, indicating an increase in docking site occupancy as a function of external calcium concentration.