Overexpression of adenosine A2A receptors in rats: effects on depression, locomotion, and anxiety

Adenosine A2A receptors (A2AR) are a sub-type of receptors enriched in basal ganglia, activated by the neuromodulator adenosine, which interact with dopamine D2 receptors. Although this reciprocal antagonistic interaction is well-established in motor function, the outcome in dopamine-related behaviors remains uncertain, in particular in depression and anxiety. We have demonstrated an upsurge of A2AR associated to aging and chronic stress. Furthermore, Alzheimer's disease patients present A2AR accumulation in cortical areas together with depressive signs. We now tested the impact of overexpressing A2AR in forebrain neurons on dopamine-related behavior, namely depression. Adult male rats overexpressing human A2AR under the control of CaMKII promoter [Tg(CaMKII-hA2AR)] and aged-matched wild-types (WT) of the same strain (Sprague-Dawley) were studied. The forced swimming test (FST), sucrose preference test (SPT), and the open-field test (OFT) were performed to evaluate behavioral despair, anhedonia, locomotion, and anxiety. Tg(CaMKII-hA2AR) animals spent more time floating and less time swimming in the FST and presented a decreased sucrose preference at 48 h in the SPT. They also covered higher distances in the OFT and spent more time in the central zone than the WT. The results indicate that Tg(CaMKII-hA2AR) rats exhibit depressive-like behavior, hyperlocomotion, and altered exploratory behavior. This A2AR overexpression may explain the depressive signs found in aging, chronic stress, and Alzheimer's disease

Age-related shift in LTD is dependent on neuronal adenosine A(2A) receptors interplay with mGluR5 and NMDA receptors

Synaptic dysfunction plays a central role in Alzheimer's disease (AD), since it drives the cognitive decline. An association between a polymorphism of the adenosine A2A receptor (A2AR) encoding gene-ADORA2A, and hippocampal volume in AD patients was recently described. In this study, we explore the synaptic function of A2AR in age-related conditions. We report, for the first time, a significant overexpression of A2AR in hippocampal neurons of aged humans, which is aggravated in AD patients. A similar profile of A2AR overexpression in rats was sufficient to drive age-like memory impairments in young animals and to uncover a hippocampal LTD-to-LTP shift. This was accompanied by increased NMDA receptor gating, dependent on mGluR5 and linked to enhanced Ca(2+) influx. We confirmed the same plasticity shift in memory-impaired aged rats and APP/PS1 mice modeling AD, which was rescued upon A2AR blockade. This A2AR/mGluR5/NMDAR interaction might prove a suitable alternative for regulating aberrant mGluR5/NMDAR signaling in AD without disrupting their constitutive activity

Euclid. III. The NISP Instrument

International audienceThe Near-Infrared Spectrometer and Photometer (NISP) on board the Euclid satellite provides multiband photometry and R>=450 slitless grism spectroscopy in the 950-2020nm wavelength range. In this reference article we illuminate the background of NISP's functional and calibration requirements, describe the instrument's integral components, and provide all its key properties. We also sketch the processes needed to understand how NISP operates and is calibrated, and its technical potentials and limitations. Links to articles providing more details and technical background are included. NISP's 16 HAWAII-2RG (H2RG) detectors with a plate scale of 0.3" pix^-1 deliver a field-of-view of 0.57deg^2. In photo mode, NISP reaches a limiting magnitude of ~24.5AB mag in three photometric exposures of about 100s exposure time, for point sources and with a signal-to-noise ratio (SNR) of 5. For spectroscopy, NISP's point-source sensitivity is a SNR = 3.5 detection of an emission line with flux ~2x10^-16erg/s/cm^2 integrated over two resolution elements of 13.4A, in 3x560s grism exposures at 1.6 mu (redshifted Ha). Our calibration includes on-ground and in-flight characterisation and monitoring of detector baseline, dark current, non-linearity, and sensitivity, to guarantee a relative photometric accuracy of better than 1.5%, and relative spectrophotometry to better than 0.7%. The wavelength calibration must be better than 5A. NISP is the state-of-the-art instrument in the NIR for all science beyond small areas available from HST and JWST - and an enormous advance due to its combination of field size and high throughput of telescope and instrument. During Euclid's 6-year survey covering 14000 deg^2 of extragalactic sky, NISP will be the backbone for determining distances of more than a billion galaxies. Its NIR data will become a rich reference imaging and spectroscopy data set for the coming decades

Euclid. I. Overview of the Euclid mission

The current standard model of cosmology successfully describes a variety of measurements, but the nature of its main ingredients, dark matter and dark energy, remains unknown. Euclid is a medium-class mission in the Cosmic Vision 2015-2025 programme of the European Space Agency (ESA) that will provide high-resolution optical imaging, as well as near-infrared imaging and spectroscopy, over about 14,000 deg^2 of extragalactic sky. In addition to accurate weak lensing and clustering measurements that probe structure formation over half of the age of the Universe, its primary probes for cosmology, these exquisite data will enable a wide range of science. This paper provides a high-level overview of the mission, summarising the survey characteristics, the various data-processing steps, and data products. We also highlight the main science objectives and expected performance

Euclid. I. Overview of the Euclid mission

International audienceThe current standard model of cosmology successfully describes a variety of measurements, but the nature of its main ingredients, dark matter and dark energy, remains unknown. Euclid is a medium-class mission in the Cosmic Vision 2015-2025 programme of the European Space Agency (ESA) that will provide high-resolution optical imaging, as well as near-infrared imaging and spectroscopy, over about 14,000 deg^2 of extragalactic sky. In addition to accurate weak lensing and clustering measurements that probe structure formation over half of the age of the Universe, its primary probes for cosmology, these exquisite data will enable a wide range of science. This paper provides a high-level overview of the mission, summarising the survey characteristics, the various data-processing steps, and data products. We also highlight the main science objectives and expected performance