Multi-messenger observations of a binary neutron star merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta

Neurobehavioral profiles of six genetically-based rat models of schizophrenia related symptoms

Schizophrenia is a chronic and severe mental disorder with high heterogeneity in its symptoms clusters. The effectiveness of drug treatments for the disorder is far from satisfactory. It is widely accepted that research with valid animal models is essential if we aim at understanding its genetic/ neurobiological mechanisms and finding more effective treatments. The present article presents an overview of six genetically-based (selectively-bred) rat models/strains, which exhibit neurobehavioral schizophrenia-relevant features, i.e., the Apomorphine-susceptible (APO-SUS) rats, the Low-prepulse inhibition rats, the Brattleboro (BRAT) rats, the Spontaneously Hypertensive rats (SHR), the Wisket rats and the Roman High-Avoidance (RHA) rats. Strikingly, all the strains display impairments in prepulse inhibition of the startle response (PPI), which remarkably, in most cases are associated with novelty-induced hyperlocomotion, deficits of social behavior, impairment of latent inhibition and cognitive flexibility, or signs of impaired prefrontal cortex (PFC) function. However, only three of the strains share PPI deficits and dopaminergic (DAergic) psychostimulant-induced hyperlocomotion (together with prefrontal cortex dysfunction in two models, the APO-SUS and RHA), which points out that alterations of the mesolimbic DAergic circuit are a schizophrenia-linked trait that not all models reproduce, but it characterizes some strains that can be valid models of schizophrenia-relevant features and drug-addiction vulnerability (and thus, dual diagnosis). We conclude by putting the research based on these genetically-selected rat models in the context of the Research Domain Criteria (RDoC) framework, suggesting that RDoC-oriented research programs using selectively-bred strains might help to accelerate progress in the various aspects of the schizophrenia-related research agenda

Decreased social interaction in the RHA rat model of schizophrenia-relevant features: Modulation by neonatal handling

The Roman-Low (RLA) and High-Avoidance (RHA) rat strains have been bidirectionally selected and bred, respectively, for extremely poor vs. rapid acquisition of the two-way active avoidance task. Over 50 years of selective breeding have led to two strains displaying many differential specific phenotypes. While RLAs display anxious-related behaviours, RHA rats show impulsivity, and schizophrenia-like positive and cognitive symptoms or phenotypes. Neonatal handling (NH) is an environmental treatment with long-lasting anxiolytic-like and anti-stress effects. NH also reduces symptoms related to schizophrenia, such as pre-pulse inhibition (PPI) impairment and latent inhibition (LI) deficits, and improves spatial working memory and cognitive flexibility. The present work was aimed at exploring whether RHAs also display negative schizophrenia-like symptoms (or phenotypes), such as lowered preference for social interaction (i.e. asociality), and whether NH would reduce these deficits. To this aim, we evaluated naïve inbred RHA and RLA rats in a social interaction (SI) test after either long- or short-term habituation to the testing set up (studies 1–2). In Study 3 we tested untreated and NH-treated RHA and RLA rats in novel object exploration (NOE) and SI tests. Compared with RHAs, RLA rats displayed increased anxiety-related behaviours in the NOE (i.e. higher behavioural inhibition, lesser exploration of the novel object) and SI (i.e. higher levels of self-grooming) tests which were dramatically reduced by NH treatment, thus supporting the long-lasting anxiolytic-like effect of NH. Remarkably, RHA rats showed decreased social preference in the SI test compared with RLAs, evidencing that RHAs would present a relative asociality, which is thought to model some negative symptomatology (i.e. social withdrawal) of schizophrenia. NH increased absolute levels of social behaviour in both strains, but with a more marked effect in RHA rats, especially in the first 5 min of the SI test. Thus, it is hypothesized that, apart from its effects on anxiety-related behaviours, NH might have long-lasting positive effects on behavioural and neurobiological processes that are impaired in schizophrenia

Differential effects of antipsychotic and propsychotic drugs on prepulse inhibition and locomotor activity in Roman high- (RHA) and low-avoidance (RLA) rats. Psychopharmacology (Berl).

Animal models with predictive and construct validity are necessary for developing novel and efficient therapeutics for psychiatric disorders. We have carried out a pharmacological characterization of the Roman high- (RHA-I) and low-avoidance (RLA-I) rat strains with different acutely administered propsychotic (DOI, MK-801) and antipsychotic drugs (haloperidol, clozapine), as well as apomorphine, on prepulse inhibition (PPI) of startle and locomotor activity (activity cages). RHA-I rats display a consistent deficit of PPI compared with RLA-I rats. The typical antipsychotic haloperidol (dopamine D2 receptor antagonist) reversed the PPI deficit characteristic of RHA-I rats (in particular at 65 and 70 dB prepulse intensities) and reduced locomotion in both strains. The atypical antipsychotic clozapine (serotonin/dopamine receptor antagonist) did not affect PPI in either strain, but decreased locomotion in a dose-dependent manner in both rat strains. The mixed dopamine D1/D2 agonist, apomorphine, at the dose of 0.05 mg/kg, decreased PPI in RHA-I, but not RLA-I rats. The hallucinogen drug DOI (5-HT2A agonist; 0.1-1.0 mg/kg) disrupted PPI in RLA-I rats in a dose-dependent manner at the 70 dB prepulse intensity, while in RHA-I rats, only the 0.5 mg/kg dose impaired PPI at the 80 dB prepulse intensity. DOI slightly decreased locomotion in both strains. Finally, clozapine attenuated the PPI impairment induced by the NMDA receptor antagonist MK-801 only in RLA-I rats. These results add experimental evidence to the view that RHA-I rats represent a model with predictive and construct validity of some dopamine and 5-HT2A receptor-related features of schizophrenia

Neurobehavioral and neurodevelopmental profiles of a heuristic genetic model of differential schizophrenia- and addiction-relevant features: The RHA vs. RLA rats

The Roman High-(RHA) and Low-(RLA) avoidance rat lines/strains were generated through bidirectional selective breeding for rapid (RHA) vs. extremely poor (RLA) two-way active avoidance acquisition. Compared with RLAs and other rat strains/stocks, RHAs are characterized by increased impulsivity, deficits in social behavior, novelty-induced hyper-locomotion, impaired attentional/cognitive abilities, vulnerability to psychostimulant sensitization and drug addiction. RHA rats also exhibit decreased function of the prefrontal cortex (PFC) and hippocampus, increased functional activity of the mesolimbic dopamine system and a dramatic deficit of central metabotropic glutamate-2 (mGlu2) receptors (due to a stop codon mutation at cysteine 407 in Grm2-cys407*-), along with increased density of 5-HT2A receptors in the PFC, alterations of several synaptic markers and increased density of pyramidal "thin" (immature) dendntic spines in the PFC. These characteristics suggest an immature brain of RHA rats, and are reminiscent of schizophrenia features like hypofrontality and disruption of the excitation/inhibition cortical balance. RHA rats represent a promising heuristic model of neurodevelopmental schizophrenia-relevant features and comorbidity with drug addiction vulnerability

Multi-messenger Observations of a Binary Neutron Star Merger

International audienceOn 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of $\sim 1.7\,{\rm{s}}$ with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg(2) at a luminosity distance of ${40}_{-8}^{+8}$ Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 $\,{M}_{\odot }$. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at $\sim 40\,{\rm{Mpc}}$) less than 11 hours after the merger by the One-Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ∼10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position $\sim 9$ and $\sim 16$ days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC 4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta