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GABAergic circuits are critical for the synchronization and higher order function of brain networks. Defects in this circuitry are linked to neuropsychiatric diseases, including bipolar disorder, schizophrenia, and autism. Work in cultured neurons has shown that ankyrin-G plays a key role in the regulation of GABAergic synapses on the axon initial segment and somatodendritic domain of pyramidal neurons, where it interacts directly with the GABAA receptor-associated protein (GABARAP) to stabilize cell surface GABAA receptors. Here, we generated a knock-in mouse model expressing a mutation that abolishes the ankyrin-G/GABARAP interaction (Ank3 W1989R) to understand how ankyrin-G and GABARAP regulate GABAergic circuitry in vivo. We found that Ank3 W1989R mice exhibit a striking reduction in forebrain GABAergic synapses resulting in pyramidal cell hyperexcitability and disruptions in network synchronization. In addition, we identified changes in pyramidal cell dendritic spines and axon initial segments consistent with compensation for hyperexcitability. Finally, we identified the ANK3 W1989R variant in a family with bipolar disorder, suggesting a potential role of this variant in disease. Our results highlight the importance of ankyrin-G in regulating forebrain circuitry and provide novel insights into how ANK3 loss-of-function variants may contribute to human disease.

Fast radio bursts (FRBs) are millisecond-duration radio transients 1 , 2 of unknown origin. Two possible mechanisms that could generate extremely coherent emission from FRBs invoke neutron star magnetospheres 3 – 5 or relativistic shocks far from the central energy source 6 – 8 . Detailed polarization observations may help us to understand the emission mechanism. However, the available FRB polarization data have been perplexing, because they show a host of polarimetric properties, including either a constant polarization angle during each burst for some repeaters 9 , 10 or variable polarization angles in some other apparently one-off events 11 , 12 . Here we report observations of 15 bursts from FRB 180301 and find various polarization angle swings in seven of them. The diversity of the polarization angle features of these bursts is consistent with a magnetospheric origin of the radio emission, and disfavours the radiation models invoking relativistic shocks. Polarization observations of the fast radio burst FRB 180301 with the FAST radio telescope show diverse polarization angle swings, consistent with a magnetospheric origin of the emission.

In the original version of this article, affiliation 3 was given as: “Division of Life Sciences, State Key Laboratory of Molecular Neuroscience, Hong Kong, University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China”. This has now been corrected to: “Division of Life Sciences, State Key Laboratory of Molecular Neuroscience, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China”.Additionally in the ‘Data availability’ section an incorrect accession code was given. The accession code has now been changed from ‘PDB A9X (AnkG:GABARAPL)’ to ‘PDB 6A9X (AnkG:GABARAP)’.These errors have been corrected in both the PDF and HTML versions of the Article.

High-precision pulsar timing is central to a wide range of astrophysics and fundamental physics applications. When timing an ensemble of millisecond pulsars in different sky positions, known as a pulsar timing array (PTA), one can search for ultra-low-frequency gravitational waves (GWs) through the spatial correlations that spacetime deformations by passing GWs are predicted to induce on the pulses’ times-of-arrival (TOAs). A pulsar-timing model, requires the use of a solar-system ephemeris (SSE) to properly predict the position of the solar-system barycentre, the (quasi-)inertial frame where all TOAs are referred. Here, I discuss how while errors in SSEs can introduce correlations in the TOAs that may interfere with GW searches, one can make use of PTAs to study the solar system. I discuss work done within the context of the European Pulsar Timing Array and the International Pulsar Timing Array collaborations. These include new updates on the masses of planets from PTA data, first limits on masses of the most massive asteroids, and comparisons between SSEs from independent groups. Finally, I discuss a new approach in setting limits on the masses of unknown bodies in the solar system and calculate mass sensitivity curves for PTA data.

High-precision pulsar timing is central to a wide range of astrophysics and fundamental physics applications. When timing an ensemble of millisecond pulsars in different sky positions, known as a pulsar timing array (PTA), one can search for ultra-low-frequency gravitational waves (GWs) through the spatial correlations that spacetime deformations by passing GWs are predicted to induce on the pulses' times-of-arrival (TOAs). A pulsar-timing model, requires the use of a solar-system ephemeris (SSE) to properly predict the position of the solar-system barycentre, the (quasi-)inertial frame where all TOAs are referred. Here, I discuss how while errors in SSEs can introduce correlations in the TOAs that may interfere with GW searches, one can make use of PTAs to study the solar system. I discuss work done within the context of the European Pulsar Timing Array and the International Pulsar Timing Array collaborations. These include new updates on the masses of planets from PTA data, first limits on masses of the most massive asteroids, and comparisons between SSEs from independent groups. Finally, I discuss a new approach in setting limits on the masses of unknown bodies in the solar system and calculate mass sensitivity curves for PTA data.

We search for a stochastic gravitational wave background (SGWB) generated by a network of cosmic strings using six millisecond pulsars from Data Release 2 (DR2) of the European Pulsar Timing Array (EPTA). We perform a Bayesian analysis considering two models for the network of cosmic string loops, and compare it to a simple power-law model which is expected from the population of supermassive black hole binaries. Our main strong assumption is that the previously reported common red noise process is a SGWB. We find that the one-parameter cosmic string model is slightly favored over a power-law model thanks to its simplicity. If we assume a two-component stochastic signal in the data (supermassive black hole binary population and the signal from cosmic strings), we get a \\(95\\%\\) upper limit on the string tension of \\(\\log_{10}(G\\mu) < -9.9\\) (\\(-10.5\\)) for the two cosmic string models we consider. In extended two-parameter string models, we were unable to constrain the number of kinks. We test two approximate and fast Bayesian data analysis methods against the most rigorous analysis and find consistent results. These two fast and efficient methods are applicable to all SGWBs, independent of their source, and will be crucial for analysis of extended data sets.

Pulsar Timing Array experiments probe the presence of possible scalar or pseudoscalar ultralight dark matter particles through decade-long timing of an ensemble of galactic millisecond radio pulsars. With the second data release of the European Pulsar Timing Array, we focus on the most robust scenario, in which dark matter interacts only gravitationally with ordinary baryonic matter. Our results show that ultralight particles with masses \\(10^{-24.0}~\\text{eV} \\lesssim m \\lesssim 10^{-23.3}~\\text{eV}\\) cannot constitute \\(100\\%\\) of the measured local dark matter density, but can have at most local density \\(\\rho\\lesssim 0.3\\) GeV/cm\\(^3\\).

Pulsar timing arrays offer a probe of the low-frequency gravitational wave spectrum (1 - 100 nanohertz), which is intimately connected to a number of markers that can uniquely trace the formation and evolution of the Universe. We present the dataset and the results of the timing analysis from the second data release of the European Pulsar Timing Array (EPTA). The dataset contains high-precision pulsar timing data from 25 millisecond pulsars collected with the five largest radio telescopes in Europe, as well as the Large European Array for Pulsars. The dataset forms the foundation for the search for gravitational waves by the EPTA, presented in associated papers. We describe the dataset and present the results of the frequentist and Bayesian pulsar timing analysis for individual millisecond pulsars that have been observed over the last ~25 years. We discuss the improvements to the individual pulsar parameter estimates, as well as new measurements of the physical properties of these pulsars and their companions. This data release extends the dataset from EPTA Data Release 1 up to the beginning of 2021, with individual pulsar datasets with timespans ranging from 14 to 25 years. These lead to improved constraints on annual parallaxes, secular variation of the orbital period, and Shapiro delay for a number of sources. Based on these results, we derived astrophysical parameters that include distances, transverse velocities, binary pulsar masses, and annual orbital parallaxes.

Pulsar timing arrays (PTAs) can be used to study the Solar-system ephemeris (SSE), the errors of which can lead to correlated timing residuals and significantly contribute to the PTA noise budget. Most Solar-system studies with PTAs assume the dominance of the term from the shift of the Solar-system barycentre (SSB). However, it is unclear to which extent this approximation can be valid, since the perturbations on the planetary orbits may become important as data precision keeps increasing. To better understand the effects of SSE uncertainties on pulsar timing, we develop the LINIMOSS dynamical model of the Solar system, based on the SSE of Guangyu Li. Using the same input parameters as DE435, the calculated planetary positions by LINIMOSS are compatible with DE435 at centimetre level over a 20-year timespan, which is sufficiently precise for pulsar-timing applications. We utilize LINIMOSS to investigate the effects of SSE errors on pulsar timing in a fully dynamical way, by perturbing one SSE parameter per trial and examining the induced timing residuals. For the outer planets, the timing residuals are dominated by the SSB shift, as assumed in previous work. For the inner planets, the variations in the orbit of the Earth are more prominent, making previously adopted assumptions insufficient. The power spectra of the timing residuals have complex structures, which may introduce false signals in the search of gravitational waves. We also study how to infer the SSE parameters using PTAs, and calculate the accuracy of parameter estimation.