Nanoscale molecular reorganization of the inhibitory postsynaptic density is a determinant of gabaergic synaptic potentiation

Gephyrin is a key scaffold protein mediating the anchoring of GABAA receptors at inhibitory synapses. Here, we exploited superresolution techniques combined with proximity-based clustering analysis and model simulations to investigate the single-molecule gephyrin reorganization during plasticity of inhibitory synapses in mouse hippocampal cultured neurons. This approach revealed that, during the expression of inhibitory LTP, the increase of gephyrin density at postsynaptic sites is associated with the promoted formation of gephyrin nanodomains. We demonstrate that the gephyrin rearrangement in nanodomains stabilizes the amplitude of postsynaptic currents, indicating that, in addition to the number of synaptic GABAA receptors, the nanoscale distribution of GABAA receptors in the postsynaptic area is a crucial determinant for the expression of inhibitory synaptic plasticity. In addition, the methodology implemented here clears the way to the application of the graph-based theory to single-molecule data for the description and quantification of the spatial organization of the synapse at the single-molecule level

Hypersensitivity Drug Reactions (HDR) In Latin America : Similarities and Differences Between Children and Adults

HDR are frequent motives for consultation in Allergology services. Possible etiologic factors and clinical presentation differences between Latin American children and adults have not been described yet.Facultad de Ciencias Médica

Drug-induced anaphylaxis, elicitors, risk factors, and management in Latin America

Nonsteroidal anti-inflammatory drugs were the most frequent triggers of drug-induced anaphylaxis in Latín America, whereas antibiotics elicited faster onset and more scvere reactions. An improvement was observed in epinephrinc use and adherence to guidelines in the emergency department treatment of anaphylaxis in Latín America compared with our last report.Facultad de Ciencias Médica

Quantitative Super-Resolution Microscopy of Proteins at the Synaptic Level

Single-molecule localization (SML) techniques provide a powerful tool to answer biological questions requiring the observation of subcellular structures at the nanoscale. Quantitative single-molecule analysis allows quantifying the number and distribution of molecules in several biological systems beyond the diffraction limit [1]. In the last few years, many computational methods employing clustering analysis algorithms have been developed to extract quantitative information from SML data sets. In neuroscience, quantitative SML has been applied to reveal density and spatial organization of synaptic protein

Unveiling the Inhibitory Synapse Organization Using Superresolution Microscopy

The advent of super-resolution microscopy provided both a substantial improvement of the spatial resolution and the possibility to perform quantitative measurements at a nanometric level. In particular, single-molecule localization (SML) techniques provide a powerful tool to answer biological questions that require the observation of subcellular structures. Quantitative single-molecule analysis allows quantifying the number and observing the distribution of molecules in several biological systems beyond the diffraction limit [1]. In the last few years, many computational methods employing clustering analysis algorithms [2] have been developed to extract quantitative information from SML data sets