Novel Approaches to Monitor and Manipulate Single Neurons In Vivo

The complexity of the vertebrate brain poses an enormous challenge to experimental neuroscience. One way of dealing with this complexity has been to investigate different aspects of brain function in widely different preparations, each best suited to address a particular question. Accordingly, cellular questions are typically addressed with intracellular recordings in in vitro preparations such as brain slices or neuronal cultures, whereas network behavior and sensory or motor response properties are analyzed in vivo, often with extracellular recordings. This division of labor has proved to be an experimentally effective strategy. However, although there seems to be no limit to the wealth of data that can be generated in this way, integrating results derived in different preparations comes with its own set of challenges. The enormous difficulties encountered when one attempts to link cellular phenomena such as synaptic plasticity to systems properties such as spatial memory (Martin et al., 2000) have shown us that close collaboration between molecular−cellular and systems neuroscience is required (Tonegawa et al., 2003) and that we need more convergence of experimental techniques to analyze the cellular basis of neural function under more natural conditions. Studying neurons under naturalistic conditions is, however, easier said than done. A return to in vivo preparations will only be successful if we are able to solve the technical problems that led previous researchers to abandon the study of intact brains in the first place. Thus, studying neurons at the cellular level in vertebrate brains is today first and foremost a technological challenge. Here we highlight recent efforts to improve our ability to analyze functions of single neurons in vivo. Given th

Mechanisms underlying a thalamocortical transformation during active tactile sensation

During active somatosensation, neural signals expected from movement of the sensors are suppressed in the cortex, whereas information related to touch is enhanced. This tactile suppression underlies low-noise encoding of relevant tactile features and the brain’s ability to make fine tactile discriminations. Layer (L) 4 excitatory neurons in the barrel cortex, the major target of the somatosensory thalamus (VPM), respond to touch, but have low spike rates and low sensitivity to the movement of whiskers. Most neurons in VPM respond to touch and also show an increase in spike rate with whisker movement. Therefore, signals related to self-movement are suppressed in L4. Fast-spiking (FS) interneurons in L4 show similar dynamics to VPM neurons. Stimulation of halorhodopsin in FS interneurons causes a reduction in FS neuron activity and an increase in L4 excitatory neuron activity. This decrease of activity of L4 FS neurons contradicts the "paradoxical effect" predicted in networks stabilized by inhibition and in strongly-coupled networks. To explain these observations, we constructed a model of the L4 circuit, with connectivity constrained by in vitro measurements. The model explores the various synaptic conductance strengths for which L4 FS neurons actively suppress baseline and movement-related activity in layer 4 excitatory neurons. Feedforward inhibition, in concert with recurrent intracortical circuitry, produces tactile suppression. Synaptic delays in feedforward inhibition allow transmission of temporally brief volleys of activity associated with touch. Our model provides a mechanistic explanation of a behavior-related computation implemented by the thalamocortical circuit

Search for gravitational waves from Scorpius X-1 in the second Advanced LIGO observing run with an improved hidden Markov model

We present results from a semicoherent search for continuous gravitational waves from the low-mass x-ray binary Scorpius X-1, using a hidden Markov model (HMM) to track spin wandering. This search improves on previous HMM-based searches of LIGO data by using an improved frequency domain matched filter, the J-statistic, and by analyzing data from Advanced LIGO's second observing run. In the frequency range searched, from 60 to 650 Hz, we find no evidence of gravitational radiation. At 194.6 Hz, the most sensitive search frequency, we report an upper limit on gravitational wave strain (at 95% confidence) of h095%=3.47×10-25 when marginalizing over source inclination angle. This is the most sensitive search for Scorpius X-1, to date, that is specifically designed to be robust in the presence of spin wandering. © 2019 American Physical Society

Search for Tensor, Vector, and Scalar Polarizations in the Stochastic Gravitational-Wave Background

The detection of gravitational waves with Advanced LIGO and Advanced Virgo has enabled novel tests of general relativity, including direct study of the polarization of gravitational waves. While general relativity allows for only two tensor gravitational-wave polarizations, general metric theories can additionally predict two vector and two scalar polarizations. The polarization of gravitational waves is encoded in the spectral shape of the stochastic gravitational-wave background, formed by the superposition of cosmological and individually unresolved astrophysical sources. Using data recorded by Advanced LIGO during its first observing run, we search for a stochastic background of generically polarized gravitational waves. We find no evidence for a background of any polarization, and place the first direct bounds on the contributions of vector and scalar polarizations to the stochastic background. Under log-uniform priors for the energy in each polarization, we limit the energy densities of tensor, vector, and scalar modes at 95% credibility to Ω0T<5.58×10-8, Ω0V<6.35×10-8, and Ω0S<1.08×10-7 at a reference frequency f0=25 Hz. © 2018 American Physical Society

Erratum: "A Gravitational-wave Measurement of the Hubble Constant Following the Second Observing Run of Advanced LIGO and Virgo" (2021, ApJ, 909, 218)

[no abstract available

On the progenitor of binary neutron star merger GW170817

On 2017 August 17 the merger of two compact objects with masses consistent with two neutron stars was discovered through gravitational-wave (GW170817), gamma-ray (GRB 170817A), and optical (SSS17a/AT 2017gfo) observations. The optical source was associated with the early-type galaxy NGC 4993 at a distance of just ∼40 Mpc, consistent with the gravitational-wave measurement, and the merger was localized to be at a projected distance of ∼2 kpc away from the galaxy's center. We use this minimal set of facts and the mass posteriors of the two neutron stars to derive the first constraints on the progenitor of GW170817 at the time of the second supernova (SN). We generate simulated progenitor populations and follow the three-dimensional kinematic evolution from binary neutron star (BNS) birth to the merger time, accounting for pre-SN galactic motion, for considerably different input distributions of the progenitor mass, pre-SN semimajor axis, and SN-kick velocity. Though not considerably tight, we find these constraints to be comparable to those for Galactic BNS progenitors. The derived constraints are very strongly influenced by the requirement of keeping the binary bound after the second SN and having the merger occur relatively close to the center of the galaxy. These constraints are insensitive to the galaxy's star formation history, provided the stellar populations are older than 1 Gyr

Expansion and fragment settlement of the non-native seagrass Halophila stipulacea in a Caribbean bay

The non-native seagrass species Halophila stipulacea has spread throughout the Eastern Caribbean since 2002, and could potentially impact the functioning of local seagrass ecosystems. Important characteristics for invasiveness, such as dispersal, recruitment and expansion of H. stipulacea at a local scale, are unknown. We assessed H. stipulacea expansion rates within Lac Bay, Bonaire, Dutch Caribbean (7 km2), since its establishment in 2010 and tested the settlement potential of uprooted vegetative fragments of H. stipulacea. Using 49 fixed locations, we observed that between 2011 and 2015 the occurrence of H. stipulacea in the bay increased significantly from 6% to 20% while native Thalassia testudinum occurrence decreased significantly from 53% to 33%. Free-floating H. stipulacea fragments that were collected and tethered above the sediment rooted within 10 days with a settlement success rate of 100%. The growth of settled fragments was on average 0.91 shoots d−1. The ongoing shift from native T. testudinum to introduced H. stipulacea dominated meadows may have important consequences for multiple Caribbean seagrass ecosystem functions. Given the large difference in size between the two seagrass species, functions such as coastal protection, habitat structure, food availability, and the stability and resilience of these systems can be altered. The next steps towards modelling future expansion of H. stipulacea throughout the Caribbean and beyond should include the assessment of fragment viability and dispersal distance, and the impacts of natural and anthropogenic disturbance on vegetative fragment density, dispersion and settlement by this species.</p

The duration of fetal antenatal steroid exposure determines the durability of preterm ovine lung maturation

Objective Antenatal corticosteroids (ACS) are the standard of care for maturing the fetal lung and improving outcomes for preterm infants. ACS dosing remains un-optimized, and there is little understanding of how different treatment to delivery intervals may affect treatment efficacy. The durability of a lung maturational response is important because the majority of women treated with ACS do not deliver within the widely accepted 1-7 day window of treatment efficacy. We used a sheep model to test duration of fetal exposures for efficacy at delivery intervals from 1 to 10 days. Methods For infusion studies, ewes with single fetuses were randomised to receive an intravenous bolus and maintenance infusion of betamethasone phosphate to target 1-4ng/mL fetal plasma betamethasone for 36 hours, with delivery at either 2, 4 or 7 days-post treatment or sterile saline as control. Animals receiving the clinical treatment were randomised to receive either:i) a single injection of 0.25mg/kg with a 1:1 mixture of betamethasone phosphate + betamethasone acetate with delivery at either 1 or 7 days post treatment; or ii) two treatments of 0.25 mg/kg betamethasone phosphate + betamethasone acetate spaced at 24 hours (giving approximately 48 hours of fetal steroid exposure) with delivery at 2, 5, 7 or 10 days post-treatment. Negative control animals were treated with saline. All lambs were delivered at 121±3 days gestational age and ventilated for 30 minutes to assess lung function. Results Preterm lambs delivered at 1 or 2 days post-ACS treatment had significant improvements in lung maturation for both intravenous and single dose intramuscular treatments. After 2 days the efficacy of 36 hour betamethasone phosphate infusions was lost. The single dose of 1:1 betamethasone phosphate + betamethasone acetate also was ineffective at 7 days. In contrast, animals treated with two doses had significant improvements in lung maturation at 2, 5 and 7 days, with treatment efficacy reduced by 10 days. Conclusion In preterm lambs, the durability of ACS treatment depends on the duration of fetal exposure and is independent of the IV or IM maternal route of administration. For acute 24-48 hour post-treatment deliveries, a 24 hour fetal ACS exposure was sufficient for lung maturation. A fetal exposure duration of at least 48 hours was necessary to maintain long-term treatment durability. A single dose ACS treatment should be sufficient for women delivering within <48 hours of ACS treatment