Optimising the energetic cost of the glutamatergic synapse

As for electronic computation, neural information processing is energetically expensive. This is because information is coded in the brain as membrane voltage changes, which are generated largely by passive ion movements down electrochemical gradients, and these ion movements later need to be reversed by active ATP-dependent ion pumping. This article will review how much of the energetic cost of the brain reflects the activity of glutamatergic synapses, consider the relative amount of energy used pre- and postsynaptically, outline how evolution has energetically optimised synapse function by adjusting the presynaptic release probability and the postsynaptic number of glutamate receptors, and speculate on how energy use by synapses may be sensed and adjusted

HyperGal: hyperspectral scene modeling for supernova typing with the Integral Field Spectrograph SEDmachine

Recent developments in time domain astronomy, like the Zwicky Transient Facility, have made possible a daily scan of the entire visible sky, leading to the discovery of hundreds of new transients every night. Among them, 10 to 15 are supernovae (SNe), which have to be classified prior to cosmological use. The Spectral Energy Distribution machine (SEDm), a low resolution Integral Field Spectrograph, has been designed, built, and operated to spectroscopically classify targets detected by the ZTF main camera. The current Pysedm pipeline is limited by contamination when the transient is too close to its host galaxy core; this can lead to an incorrect typing and ultimately bias the cosmological analyses, and affect the SN sample homogeneity in terms of local environment properties. We present a new scene modeler to extract the transient spectrum from its structured background, aiming at improving the typing efficiency of the SEDm. HyperGal is a fully chromatic scene modeler, which uses pre-transient photometric images to generate a hyperspectral model of the host galaxy; it is based on the CIGALE SED fitter used as a physically-motivated spectral interpolator. The galaxy model, complemented by a point source and a diffuse background component, is projected onto the SEDm spectro-spatial observation space and adjusted to observations. The full procedure is validated on 5000 simulated cubes. We introduce the contrast as the transient-to-total flux ratio at SN location. From estimated contrast distribution of real SEDm observations, we show that HyperGal correctly classifies ~95% of SNe Ia. Compared to the standard extraction method, HyperGal correctly classifies 10% more SNe Ia. The false positive rate is less than 2%, half as much as the standard extraction method. Assuming a similar contrast distribution for core-collapse SNe, HyperGal classifies 14% (11%) additional SNe II (Ibc).Comment: 14 pages, 17 figures, submitted to Astronomy & Astrophysic

Astrocyte Ca2+-evoked ATP release regulates myelinated axon excitability and conduction speed*

INTRODUCTION: Astrocytes support neuronal function throughout the central nervous system. In the gray matter, they regulate synapse number during development, remove synaptically released neurotransmitters to terminate their action and prevent excitotoxicity, control the extracellular potassium concentration to prevent hyperexcitability, regulate blood flow to ensure an adequate energy supply, provide lactate to neurons for energy, and respond to rises of intracellular calcium concentration ([Ca2+]i) by releasing adenosine triphosphate (ATP) and other gliotransmitters that act on neuronal receptors to modulate information processing. However, their role is unclear in the white matter, which transmits information rapidly between gray matter areas using axons wrapped with capacitance-reducing myelin (although they have been suggested to regulate myelination during development and during normal function). RATIONALE: Recently, it has been suggested that learning and memory may reflect not only changes in synaptic function in the gray matter, but also changes in white matter function. In particular, neural circuit function might be regulated by changes in the conduction speed of myelinated axons that result in an altered arrival time of action potentials at a distant neuron. These speed changes might be brought about by alterations of the properties of the passively conducting myelinated internodes or of the intervening excitable nodes of Ranvier, where the action potential is generated. We applied immunohistochemistry to assess how astrocytes interact with myelinated axons, neuronal stimulation and light-evoked calcium uncaging in astrocytes to evoke Ca2+-dependent release of gliotransmitters, and electrophysiology and pharmacology to characterize how astrocyte-released substances might affect the axon initial segment (AIS) and nodes of Ranvier of myelinated neurons. Measurements of conduction velocity and computer modeling allowed us to interpret the results. RESULTS: Astrocytes closely approach the axons of myelinated neurons in layer V of the cerebral cortex that enter the corpus callosum. Uncaging Ca2+ within astrocytes or stimulating spike trains in neurons evoked a rise of astrocyte [Ca2+]i that triggered the release of ATP-containing vesicles from these cells. This evoked an inward current in the AIS and nodes of Ranvier of the pyramidal neurons. Pharmacology showed that this was mediated by the activation of Gs-linked adenosine A2a receptors (A2aRs), implying that the released ATP was converted to adenosine by extracellular enzymes. The A2aRs raise the intracellular concentration of cyclic AMP, which activates hyperpolarization-activated cyclic nucleotide–gated (HCN) channels mediating the inward hyperpolarization-activated current (Ih) and thus depolarizes the cell. In the AIS, the activation of A2aRs alters excitability and hence action potential generation, whereas in the nodes of Ranvier, it decreases the conduction speed of the action potential along the axon. CONCLUSION: As in the gray matter, astrocyte [Ca2+]i regulates the release of ATP into the extracellular space in the white matter. After conversion to adenosine, this regulates the excitability and conduction speed of myelinated axons. The changes in excitability at the AIS will lead to changes in the relationship between the synaptic input and action potential output of the cell. The altered conduction speed of the myelinated axon may change neural circuit function by changing the action potential arrival time at the cell’s output synapses, thus altering the integration of signals in postsynaptic neurons. Variations in astrocyte-derived adenosine level can occur between wake and sleep states, and the extracellular adenosine concentration rises during energy deprivation conditions. These changes in adenosine level could thus control white matter information flow and neural circuit function

Astrocyte Ca2+-evoked ATP release regulates myelinated axon excitability and conduction speed

INTRODUCTION: Astrocytes support neuronal function throughout the central nervous system. In the gray matter, they regulate synapse number during development, remove synaptically released neurotransmitters to terminate their action and prevent excitotoxicity, control the extracellular potassium concentration to prevent hyperexcitability, regulate blood flow to ensure an adequate energy supply, provide lactate to neurons for energy, and respond to rises of intracellular calcium concentration ([Ca2+]i) by releasing adenosine triphosphate (ATP) and other gliotransmitters that act on neuronal receptors to modulate information processing. However, their role is unclear in the white matter, which transmits information rapidly between gray matter areas using axons wrapped with capacitance-reducing myelin (although they have been suggested to regulate myelination during development and during normal function). RATIONALE: Recently, it has been suggested that learning and memory may reflect not only changes in synaptic function in the gray matter, but also changes in white matter function. In particular, neural circuit function might be regulated by changes in the conduction speed of myelinated axons that result in an altered arrival time of action potentials at a distant neuron. These speed changes might be brought about by alterations of the properties of the passively conducting myelinated internodes or of the intervening excitable nodes of Ranvier, where the action potential is generated. We applied immunohistochemistry to assess how astrocytes interact with myelinated axons, neuronal stimulation and light-evoked calcium uncaging in astrocytes to evoke Ca2+-dependent release of gliotransmitters, and electrophysiology and pharmacology to characterize how astrocyte-released substances might affect the axon initial segment (AIS) and nodes of Ranvier of myelinated neurons. Measurements of conduction velocity and computer modeling allowed us to interpret the results. RESULTS: Astrocytes closely approach the axons of myelinated neurons in layer V of the cerebral cortex that enter the corpus callosum. Uncaging Ca2+ within astrocytes or stimulating spike trains in neurons evoked a rise of astrocyte [Ca2+]i that triggered the release of ATP-containing vesicles from these cells. This evoked an inward current in the AIS and nodes of Ranvier of the pyramidal neurons. Pharmacology showed that this was mediated by the activation of Gs-linked adenosine A2a receptors (A2aRs), implying that the released ATP was converted to adenosine by extracellular enzymes. The A2aRs raise the intracellular concentration of cyclic AMP, which activates hyperpolarization-activated cyclic nucleotide–gated (HCN) channels mediating the inward hyperpolarization-activated current (Ih) and thus depolarizes the cell. In the AIS, the activation of A2aRs alters excitability and hence action potential generation, whereas in the nodes of Ranvier, it decreases the conduction speed of the action potential along the axon. CONCLUSION: As in the gray matter, astrocyte [Ca2+]i regulates the release of ATP into the extracellular space in the white matter. After conversion to adenosine, this regulates the excitability and conduction speed of myelinated axons. The changes in excitability at the AIS will lead to changes in the relationship between the synaptic input and action potential output of the cell. The altered conduction speed of the myelinated axon may change neural circuit function by changing the action potential arrival time at the cell’s output synapses, thus altering the integration of signals in postsynaptic neurons. Variations in astrocyte-derived adenosine level can occur between wake and sleep states, and the extracellular adenosine concentration rises during energy deprivation conditions. These changes in adenosine level could thus control white matter information flow and neural circuit function

Evaluation of the Parasight Platform for Malaria Diagnosis

The World Health Organization estimates that nearly 500 million malaria tests are performed annually. While microscopy and rapid diagnostic tests (RDTs) are the main diagnostic approaches, no single method is inexpensive, rapid, and highly accurate. Two recent studies from our group have demonstrated a prototype computer vision platform that meets those needs. Here we present the results from two clinical studies on the commercially available version of this technology, the Sight Diagnostics Parasight platform, which provides malaria diagnosis, species identification, and parasite quantification. We conducted a multisite trial in Chennai, India (Apollo Hospital [n = 205]), and Nairobi, Kenya (Aga Khan University Hospital [n = 263]), in which we compared the device to microscopy, RDTs, and PCR. For identification of malaria, the device performed similarly well in both contexts (sensitivity of 99% and specificity of 100% at the Indian site and sensitivity of 99.3% and specificity of 98.9% at the Kenyan site, compared to PCR). For species identification, the device correctly identified 100% of samples with Plasmodium vivax and 100% of samples with Plasmodium falciparum in India and 100% of samples with P. vivax and 96.1% of samples with P. falciparum in Kenya, compared to PCR. Lastly, comparisons of the device parasite counts with those of trained microscopists produced average Pearson correlation coefficients of 0.84 at the Indian site and 0.85 at the Kenyan site

A radio-detected type Ia supernova with helium-rich circumstellar material

Type Ia supernovae (SNe Ia) are thermonuclear explosions of degenerate white dwarf stars destabilized by mass accretion from a companion star 1, but the nature of their progenitors remains poorly understood. A way to discriminate between progenitor systems is through radio observations; a non-degenerate companion star is expected to lose material through winds 2 or binary interaction 3 before explosion, and the supernova ejecta crashing into this nearby circumstellar material should result in radio synchrotron emission. However, despite extensive efforts, no type Ia supernova (SN Ia) has ever been detected at radio wavelengths, which suggests a clean environment and a companion star that is itself a degenerate white dwarf star 4,5. Here we report on the study of SN 2020eyj, a SN Ia showing helium-rich circumstellar material, as demonstrated by its spectral features, infrared emission and, for the first time in a SN Ia to our knowledge, a radio counterpart. On the basis of our modelling, we conclude that the circumstellar material probably originates from a single-degenerate binary system in which a white dwarf accretes material from a helium donor star, an often proposed formation channel for SNe Ia (refs. 6,7). We describe how comprehensive radio follow-up of SN 2020eyj-like SNe Ia can improve the constraints on their progenitor systems

HyperGal: hyperspectral scene modeling for supernova typing with the Integral Field Spectrograph SEDmachine

Recent developments in time domain astronomy, like the Zwicky Transient Facility, have made possible a daily scan of the entire visible sky, leading to the discovery of hundreds of new transients every night. Among them, 10 to 15 are supernovae (SNe), which have to be classified prior to cosmological use. The Spectral Energy Distribution machine (SEDm), a low resolution Integral Field Spectrograph, has been designed, built, and operated to spectroscopically classify targets detected by the ZTF main camera. The current Pysedm pipeline is limited by contamination when the transient is too close to its host galaxy core; this can lead to an incorrect typing and ultimately bias the cosmological analyses, and affect the SN sample homogeneity in terms of local environment properties. We present a new scene modeler to extract the transient spectrum from its structured background, aiming at improving the typing efficiency of the SEDm. HyperGal is a fully chromatic scene modeler, which uses pre-transient photometric images to generate a hyperspectral model of the host galaxy; it is based on the CIGALE SED fitter used as a physically-motivated spectral interpolator. The galaxy model, complemented by a point source and a diffuse background component, is projected onto the SEDm spectro-spatial observation space and adjusted to observations. The full procedure is validated on 5000 simulated cubes. We introduce the contrast as the transient-to-total flux ratio at SN location. From estimated contrast distribution of real SEDm observations, we show that HyperGal correctly classifies ~95% of SNe Ia. Compared to the standard extraction method, HyperGal correctly classifies 10% more SNe Ia. The false positive rate is less than 2%, half as much as the standard extraction method. Assuming a similar contrast distribution for core-collapse SNe, HyperGal classifies 14% (11%) additional SNe II (Ibc)

New Modules for the SEDMachine to Remove Contaminations from Cosmic Rays and Non-target Light:BYECR and CONTSEP

Abstract: Currently time-domain astronomy can scan the entire sky on a daily basis, discovering thousands of interesting transients every night. Classifying the ever-increasing number of new transients is one of the main challenges for the astronomical community. One solution that addresses this issue is the robotically controlled Spectral Energy Distribution Machine (SEDM) which supports the Zwicky Transient Facility (ZTF). SEDM with its pipeline pysedm demonstrates that real-time robotic spectroscopic classification is feasible. In an effort to improve the quality of the current SEDM data, we present here two new modules, byecr and contsep. The first removes contamination from cosmic rays, and the second removes contamination from non-target light. These new modules are part of the automated pysedm pipeline and fully integrated with the whole process. Employing byecr and contsep modules together automatically extracts more spectra than the current pysedm pipeline. Using SNID classification results, the new modules show an improvement in the classification rate and accuracy of 2.8% and 1.7%, respectively, while the strength of the cross-correlation remains the same. Improvements to the SEDM astrometry would further boost the improvement of the contsep module. This kind of robotic follow-up with a fully automated pipeline has the potential to provide the spectroscopic classifications for the transients discovered by ZTF and also by the Rubin Observatory’s Legacy Survey of Space and Time

Accuracy of environmental tracers and consequence for determining the Type Ia Supernovae magnitude step

International audienceType Ia Supernovae (SNe Ia) are standardizable candles that allow us to measure the recent expansion rate of the Universe. Due to uncertainties in progenitor physics, potential astrophysical dependencies may bias cosmological measurements if not properly accounted for. The dependency of the intrinsic luminosity of SNe Ia with their host-galaxy environment is often used to standardize SNe Ia luminosity and is commonly parameterized as a step function. This functional form implicitly assumes two-populations of SNe Ia. In the literature, multiple environmental indicators have been considered, finding different, sometimes incompatible, step function amplitudes. We compare these indicators in the context of a two-populations model, based on their ability to distinguish the two populations. We show that local H$\alpha$-based specific star formation rate (lsSFR) and global stellar mass are better tracers than, for instance, host galaxy morphology. We show that tracer accuracy can explain the discrepancy between the observed SNe Ia step amplitudes found in the literature. Using lsSFR or global mass to distinguish the two populations can explain all other observations, though lsSFR is favoured. As lsSFR is strongly connected to age, our results favour a prompt and delayed population model. In any case, there exists two populations that differ in standardized magnitude by at least $0.121\pm0.010\,\mathrm{mag}$