Presynaptic mGlu1 Receptors Control GABAB Receptors in an Antagonist-Like Manner in Mouse Cortical GABAergic and Glutamatergic Nerve Endings

Mouse cortical GABAergic synaptosomes possess presynaptic inhibitory GABAB autoreceptors. Accordingly, (\ub1)baclofen (3 \u3bcM) inhibits in a CGP53423-sensitive manner the 12 mM KCl-evoked release of preloaded [3H]GABA. Differently, the existence of presynaptic release-regulating metabotropic glutamate type 1 (mGlu1) heteroreceptors in these terminals is still matter of discussion, although confocal microscopy unveiled the existence of mGlu1\u3b1 with GABAB1 or GABAB2 proteins in cortical VGAT-positive synaptosomes. The group I mGlu agonist 3,5-DHPG failed to modify on its own the 12 mM KCl-evoked [3H]GABA exocytosis from cortical nerve endings, but, when added concomitantly to the GABAB agonist, it significantly reduced the 3 \u3bcM (\ub1)baclofen-induced inhibition of [3H]GABA exocytosis. Conversely, the mGlu1 antagonist LY367385 (0.03\u20131 \u3bcM), inactive on its own on GABA exocytosis, amplified the 3 \u3bcM (\ub1)baclofen-induced inhibition of [3H]GABA overflow. The ( \ub1 )baclofen-induced inhibition of [3H]GABA exocytosis was more pronounced in cortical synaptosomes from Grm1crv4/crv4 mice, which bear a spontaneous mutation of the Grm1 gene leading to the functional inactivation of the mGlu1 receptor. Inasmuch, the expression of GABAB2 receptor protein in cortical synaptosomal lysates from Grm1crv4/crv4 mice was increased when compared to controls. Altogether, these observations seem best interpreted by assuming that mGlu1 coexist with GABAB receptors in GABAergic cortical synaptosomes, where they control GABA receptors in an antagonist-like manner. We then asked whether the mGlu1-mediated control of GABAB receptors is restricted to GABAergic terminals, or if it occurs also in other subpopulations of nerve endings. Release-regulating GABAB receptors also exist in glutamatergic nerve endings. (\ub1)baclofen (1 \u3bcM) diminished the 12 mM KCl-evoked [3H]D-aspartate overflow. Also in these terminals, the concomitant presence of 1 \u3bcM LY367385, inactive on its own, significantly amplified the inhibitory effect exerted by (\ub1)baclofen on [3H]D-aspartate exocytosis. Confocal microscopy confirmed the colocalization of mGlu1 with GABAB1 and GABAB2 labeling in vesicular glutamate type1 transporter-positive particles. Our results support the conclusion that mGlu1 receptors modulate in an antagonist-like manner presynaptic release-regulating GABAB receptors. This receptor\u2013receptor interaction could be neuroprotective in central disease typified by hyperglutamatergicity

Presynaptic mGlu1 Receptors Control GABAB Receptors in an Antagonist-Like Manner in Mouse Cortical GABAergic and Glutamatergic Nerve Endings

Mouse cortical GABAergic synaptosomes possess presynaptic inhibitory GABAB autoreceptors. Accordingly, (±)baclofen (3 μM) inhibits in a CGP53423-sensitive manner the 12 mM KCl-evoked release of preloaded [3H]GABA. Differently, the existence of presynaptic release-regulating metabotropic glutamate type 1 (mGlu1) heteroreceptors in these terminals is still matter of discussion, although confocal microscopy unveiled the existence of mGlu1α with GABAB1 or GABAB2 proteins in cortical VGAT-positive synaptosomes. The group I mGlu agonist 3,5-DHPG failed to modify on its own the 12 mM KCl-evoked [3H]GABA exocytosis from cortical nerve endings, but, when added concomitantly to the GABAB agonist, it significantly reduced the 3 μM (±)baclofen-induced inhibition of [3H]GABA exocytosis. Conversely, the mGlu1 antagonist LY367385 (0.03–1 μM), inactive on its own on GABA exocytosis, amplified the 3 μM (±)baclofen-induced inhibition of [3H]GABA overflow. The ( ± )baclofen-induced inhibition of [3H]GABA exocytosis was more pronounced in cortical synaptosomes from Grm1crv4/crv4 mice, which bear a spontaneous mutation of the Grm1 gene leading to the functional inactivation of the mGlu1 receptor. Inasmuch, the expression of GABAB2 receptor protein in cortical synaptosomal lysates from Grm1crv4/crv4 mice was increased when compared to controls. Altogether, these observations seem best interpreted by assuming that mGlu1 coexist with GABAB receptors in GABAergic cortical synaptosomes, where they control GABA receptors in an antagonist-like manner. We then asked whether the mGlu1-mediated control of GABAB receptors is restricted to GABAergic terminals, or if it occurs also in other subpopulations of nerve endings. Release-regulating GABAB receptors also exist in glutamatergic nerve endings. (±)baclofen (1 μM) diminished the 12 mM KCl-evoked [3H]D-aspartate overflow. Also in these terminals, the concomitant presence of 1 μM LY367385, inactive on its own, significantly amplified the inhibitory effect exerted by (±)baclofen on [3H]D-aspartate exocytosis. Confocal microscopy confirmed the colocalization of mGlu1 with GABAB1 and GABAB2 labeling in vesicular glutamate type1 transporter-positive particles. Our results support the conclusion that mGlu1 receptors modulate in an antagonist-like manner presynaptic release-regulating GABAB receptors. This receptor–receptor interaction could be neuroprotective in central disease typified by hyperglutamatergicity

Coherent phase transfer for real-world twin-field quantum key distribution

Quantum mechanics allows distribution of intrinsically secure encryption keys by optical means. Twin-field quantum key distribution is one of the most promising techniques for its implementation on long-distance fiber networks, but requires stabilizing the optical length of the communication channels between parties. In proof-of-principle experiments based on spooled fibers, this was achieved by interleaving the quantum communication with periodical stabilization frames. In this approach, longer duty cycles for the key streaming come at the cost of a looser control of channel length, and a successful key-transfer using this technique in real world remains a significant challenge. Using interferometry techniques derived from frequency metrology, we develop a solution for the simultaneous key streaming and channel length control, and demonstrate it on a 206 km field-deployed fiber with 65 dB loss. Our technique reduces the quantum-bit-error-rate contributed by channel length variations to <1%, representing an effective solution for real-world quantum communications

PHREESQL: A toolkit to efficiently compute and store geochemical speciation calculation

Both abiotic and biotic natural spheres benefit from the high reactivity of natural waters, which are ubiquitous on planet Earth. The use of speciation-solubility codes like PHREEQC can provide a deeper understanding of aqueous equilibria and water-rock interactions. A significant number of newly derived variables are produced by these computations, which may significantly increase compared to input data. It is crucial to process vast amounts of data efficiently, particularly when dealing with datasets that contain thousands of water analyses. To tackle this problem, we present PHREESQL, a software package designed to efficiently store and manage extensive data generated by geochemical speciation computations performed by PHREEQC. High efficiency in data extraction and filtering of the entire output from a single run can be achieved through a well-designed relational SQL database structure. The PHREESQL can be used as a stand-alone package or embedded in third-party applications. Thanks to the SQL structure, it is possible to create links with unstructured meshes by developers and experts in reaction-transport problems. Real-time data management from multiparameter devices in field and laboratory settings is made possible and efficient by parallel computation options and software integration. The toolkit encompasses both a C++ library and a command-line interface, facilitating its use by geochemists with limited programming skills

A computational approach for 3D modeling and integration of heterogeneous geo-data

This paper tackles the volumetric representation of geophysical and geotechnical data, gathered during exploration surveys of the subsoil; in particular, we focus on the modeling and analysis of underwater deposits. The creation of a 3D model as support to geological interpretation has to take into account the heterogeneity of the input data, coming from offshore acquisition campaigns. Some data are massive, but cover the domain unevenly, e.g., along dense differently spaced lines, while others are very sparse, e.g., borehole locations with soil sampling and CPTU (Piezocone Penetration Test) locations. A automatic process is presented to generate the subsurfaces and volume defining a sub-seabed deposit, starting from the identification of relevant morphological features in seismic data. In particular, simplification and refinement based on geostatistics have been applied to generate regular 2D meshes from strongly anisotropic data, in order to improve the quality of the final 3D tetrahedral mesh. Furthermore, we also use geostatistics to predict geotechnical parameters from local surveys and estimate their distribution on the whole domain: in this way the 3D model will include relevant geological features of the deposit and allow extrapolating different geotechnical information with associated uncertainty. The volume characterization and its 3D inspection will support geological analysis and planning of future engineering activities. The developed methodology has been tested on two real case studies