The optical spectrograph and infrared imager system (OSIRIS) on board the Odin spacecraft is designed to retrieve altitude profiles of terrestrial atmospheric minor species by observing limb-radiance profiles. The grating optical spectrograph (OS) obtains spectra of scattered sunlight over the range 280-800 nm with a spectral resolution of approximately 1 nm. The Odin spacecraft performs a repetitive vertical limb scan to sweep the OS 1 km vertical field of view over selected altitude ranges from approximately 10 to 100 km. The terrestrial absorption features that are superimposed on the scattered solar spectrum are monitored to derive the minor species altitude profiles. The spectrograph also detects the airglow, which can be used to study the mesosphere and lower thermosphere. The other part of OSIRIS is a three-channel infrared imager (IRI) that uses linear array detectors to image the vertical limb radiance over an altitude range of approximately 100 km. The IRI observes both scattered sunlight and the airglow emissions from the oxygen infrared atmospheric band at 1.27 µm and the OH (3-1) Meinel band at 1.53 µm. A tomographic inversion technique is used with a series of these vertical images to derive the two-dimensional distribution of the emissions within the orbit plane.Résumé : Le système de spectrographie optique et d'imagerie infrarouge (OSIRIS) à bord du satellite Odin est conçu pour enregistrer les profils en altitude des éléments mineurs de l'atmosphère en observant les profils de radiance du limbe. Le spectrographe optique à réseau (OS) obtient les spectres de la lumière solaire diffusée sur le domaine entre 280-800 nm, avec une résolution spatiale approximative de 1 nm. Le satellite Odin balaye verticalement le limbe de façon répétée, de telle sorte que l'ouverture verticale de 1 km du OS parcoure les domaines voulus entre 10 et 100 km. Nous analysons les spectres solaires diffusés en superposition avec les caractéristiques terrestres d'absorption, afin de déterminer les profils en altitude des éléments mineurs de l'atmosphère. Le spectrographe détecte aussi la luminescence nocturne atmosphérique qui peut être utilisé pour étudier la mésosphère et la thermosphère. L'autre partie d'OSIRIS est un imageur infrarouge (IRI) à trois canaux qui utilise une banque linéaire de détecteurs pour imager la radiance du limbe sur un domaine d'altitude d'approximativement 100 km. L'IRI observe à la fois la lumière solaire diffusée et les émissions de luminescence nocturne atmospérique provenant de la bande infrarouge de l'oxygène atmosphérique à 1.27 µm et la bande de Meinel de l'OH (3-1) à 1.53 µm. Nous utilisons une technique d'inversion tomographique avec une série de ces images verticales pour obtenir la distribution bidimensionnelle des émissions à l'intérieur de l'orbite.[Traduit par la Rédaction] Can.

Modification of the number of GABA A receptors (GABA A Rs) clustered at inhibitory synapses can regulate inhibitory synapse strength with important implications for information processing and nervous system plasticity and pathology. Currently, however, the mechanisms that regulate the number of GABA A Rs at synapses remain poorly understood. By imaging superecliptic pHluorin tagged GABA A R subunits we show that synaptic GABA A R clusters are normally stable, but that increased neuronal activity upon glutamate receptor (GluR) activation results in their rapid and reversible dispersal. This dispersal correlates with increases in the mobility of single GABA A Rs within the clusters as determined using singleparticle tracking of GABA A Rs labeled with quantum dots. GluRdependent dispersal of GABA A R clusters requires Ca 2+ influx via NMDA receptors (NMDARs) and activation of the phosphatase calcineurin. Moreover, the dispersal of GABA A R clusters and increased mobility of individual GABA A Rs are dependent on serine 327 within the intracellular loop of the GABA A R γ2 subunit. Thus, NMDAR signaling, via calcineurin and a key GABA A R phosphorylation site, controls the stability of synaptic GABA A Rs, with important implications for activitydependent control of synaptic inhibition and neuronal plasticity.ion channels | plasticity | trafficking | diffusion | calcineurin S ynaptic inhibition plays a critical role in regulating neuronal excitability and information processing in the brain. The number of GABA A receptors (GABA A Rs) in the surface membrane and at synaptic sites is an important determinant of inhibitory synapse strength (1), but the mechanisms that rapidly control synaptic GABA A R number and stability remain poorly understood. Activation of Ca 2+ -permeable ionotropic glutamate receptors (GluRs) during plasticity and in pathology can result in down-modulation of inhibitory synapse strength and GABA A R function (2-5) but the molecular and cellular mechanisms underlying GluR-dependent changes in the strength of GABAergic inhibition remain unclear.A major mechanism for modulating GABA A R activity is the direct phosphorylation of residues within the intracellular loops of GABA A R subunits, which can regulate synaptic inhibition, GABA A R channel kinetics, and trafficking (6-9). The rapid movement of neurotransmitter receptors (including GABA A Rs) (10-12) into and out of synapses has also recently emerged as an important mechanism for regulating synaptic strength (13). However, whether GABA A R phosphorylation can directly regulate the synaptic stability of GABA A Rs and their lateral diffusion and movement into and out of synapses is unknown.Here, by live cell imaging of surface GABA A R clusters with pHsensitive superecliptic pHluorin (SEP) and single GABA A Rs with quantum dots (QDs), we investigate the mechanisms that regulate activity-dependent control of the lateral diffusion, clustering, and stability of GABA A Rs at inhibitory synapses. We find that Ca 2+ entry through NMDA receptors (NMDARs) l...

Summary Recent evidence implicates glutamatergic synapses as key pathogenic sites in psychiatric disorders. Common and rare variants in the ANK3 gene, encoding ankyrin-G, have been associated with bipolar disorder, schizophrenia, and autism. Here we demonstrate that ankyrin-G is integral to AMPAR-mediated synaptic transmission and maintenance of spine morphology. Using super-resolution microscopy we find that ankyrin-G forms distinct nanodomain structures within the spine head and neck. At these sites, it modulates mushroom spine structure and function, likely as a perisynaptic scaffold and barrier within the spine neck. Neuronal activity promotes ankyrin-G accumulation in distinct spine subdomains, where it differentially regulates NMDA receptor-dependent plasticity. These data implicate subsynaptic nanodomains containing a major psychiatric risk molecule, ankyrin-G, as having location-specific functions, and opens directions for basic and translational investigation of psychiatric risk molecules.

Highlights d Inhibitory synapses are composed of nanoscale subsynaptic domains (SSDs) d Gephyrin and GABA A R SSDs closely associate and are dependent on each other d GABA A R SSDs are closely associated with presynaptic active-zone SSDs d Inhibitory synapses recruit additional SSDs during activitydependent growth

The regulation of the number of ␥2-subunit-containing GABAA receptors (GABAARs) present at synapses is critical for correct synaptic inhibition and animal behavior. This regulation occurs, in part, by the controlled removal of receptors from the membrane in clathrin-coated vesicles, but it remains unclear how clathrin recruitment to surface ␥2-subunit-containing GABAARs is regulated. Here, we identify a ␥2-subunit-specific Yxx-type-binding motif for the clathrin adaptor protein, AP2, which is located within a site for ␥2-subunit tyrosine phosphorylation. Blocking GABAAR-AP2 interactions via this motif increases synaptic responses within minutes. Crystallographic and biochemical studies reveal that phosphorylation of the Yxx motif inhibits AP2 binding, leading to increased surface receptor number. In addition, the crystal structure provides an explanation for the high affinity of this motif for AP2 and suggests that ␥2-subunit-containing heteromeric GABAARs may be internalized as dimers or multimers. These data define a mechanism for tyrosine kinase regulation of GABAAR surface levels and synaptic inhibition.endocytosis ͉ phosphorylation ͉ structure ͉ synaptic transmission ͉ tyrosine kinase T he GABA A receptor (GABA A R), a ligand-gated ion channel, mediates the majority of fast inhibitory synaptic transmission in the mammalian CNS. Identifying the molecular mechanisms important for regulating these receptors is essential for our understanding of how synaptic inhibition and neuronal excitability are controlled. GABA A Rs are pentameric heterooligomers assembled from seven subunit classes (␣1-6, ␤1-3, ␥1-3, ␦, , , and ). It is generally assumed that the majority of GABA A Rs in the brain are assembled from at least 2 ␣-, 2 ␤-, and 1 ␥2-subunits (1). The GABA A R ␥2-subunit confers important pharmacological, functional, and membrane-trafficking properties to GABA A Rs, including benzodiazepine sensitivity, the selective targeting of GABA A Rs to inhibitory postsynaptic domains, and correct animal behavior (2, 3). The phosphorylation of tyrosine (Y) residues within the ␥2-subunit intracellular domain (ICD) at Y 365 and Y 367 increases GABA A R function. However, the mechanisms that underlie this regulation remain unclear (4, 5). Furthermore, it has recently been demonstrated that altered membrane trafficking of ␥2-subunit-containing GABA A Rs may underlie certain pathological conditions, such as the generation of pharmacoresistance and self-sustaining seizures in status epilepticus and the increased excitotoxicity in ischemia (6-8). Currently, little is known regarding the molecular mechanisms and protein interactions that underlie ␥2-subunit-dependent regulation of receptor membrane trafficking under normal or pathological conditions.A potential mechanism to regulate synaptic inhibition is to alter the number of surface and synaptic GABA A Rs. This surface receptor number can be determined, in part, by receptor endocytosis and the interaction with the clathrin adaptor protein (AP2) complex (9, 10). The AP2 complex...