Behavioral Outputs of Fragile-X Autistic Mice Exposed to Open-Field, Randomized, Short-Term Visual Stimuli

Animal models of different neurological disorders are required for studying the pathophysiology of these diseases, and for potential development of pharmacological and behavioral treatments. The scientific community often uses mouse models for behavior studies due to their powerful genetic tools and low cost. However, subjective measurement techniques are often used when analyzing mice for behavioral traits which often results in discrepancies in results. An automated tracking software would aim to eliminate these discrepancies and subjective analysis. This lab has developed a software program which offered an ability to automatically collect open-field behavioral data with simultaneous on-line analysis. Python, an open sourced programming language, and OpenCV, an open sourced computer vision library, were used to create this novel tracking software. Wild type and transgenic Fragile-X mice were put into an open field environment and allowed to freely interact with it. Relative positioning and cross sectional area of a mouse were automatically tracked and quantified. In addition, an open-field visual stimulation paradigm was used, which is intended to be used to test visual perception, visual learning, and behavior in mice. A statistically significant difference was found between the transgenic and wild type mice in how they respond to both novel and habituated stimulation. The transgenic mice reacted for a longer period of time after novel stimulation with no decrease in response over the 45 minutes of trials while wild type mice stopped responding immediately after stimulation ended and have a decreased response over time. The most likely cause of these responses is a difficulty learning in fragile-X mouse models as well as longer firing time for their neurons

Developing Strategies for Anatomical Characterization of Locus Coeruleus - Cortical Projections

The locus coeruleus (LC) is a small noradrenergic nucleus located in the midbrain that releases the neurotransmitter norepinephrine to diverse brain regions. Through release of norepinephrine, the LC plays a central role in modulating numerous physiological functions including attention, arousal, and mood and behavior. Although the LC projects to many brain region, there is limited information about the organization and the afferent projections to the LC that modulates its activity. The goal of this study was to characterize the anatomical projections between LC and cortical areas using a variety of different experimental techniques, including survival brain surgery, stereotaxic injections of fluorescent dyes, trans-cardiac perfusion, and immunohistochemistry. To determine cortical projections from different brain region to the locus coeruleus, we injected the retrograde fluorescent tracer Fast Blue into the LC. Immunolabeling technique using dopamine-b-hydroxylase antibody allowed for detection of norepinephrine neurons and their extensive projections. The results from the experiment after microscopic imaging of the histology slices do not reveal a direct projection from the visual cortex to the locus coeruleus

Lovastatin Corrects Excess Protein Synthesis and Prevents Epileptogenesis in a Mouse Model of Fragile X Syndrome

Many neuropsychiatric symptoms of fragile X syndrome (FXS) are believed to be a consequence of altered regulation of protein synthesis at synapses. We discovered that lovastatin, a drug that is widely prescribed for the treatment of high cholesterol, can correct excess hippocampal protein synthesis in the mouse model of FXS and can prevent one of the robust functional consequences of increased protein synthesis in FXS, epileptogenesis. These data suggest that lovastatin is potentially disease modifying and could be a viable prophylactic treatment for epileptogenesis in FXS.FRAXA Research FoundationNational Institute of Mental Health (U.S.)Eunice Kennedy Shriver National Institute of Child Health and Human Development (U.S.)Simons Foundatio

A Touchscreen Assay to Probe the Role of the Serotonergic System in Learning and Visual Information Processing

The neurotransmitter serotonin is involved in numerous processes in the brain such as behavior, learning, memory, mood, and neurodevelopment. Serotonin signaling is regulated by the serotonin transporter protein (SERT), which maintains normal serotonin levels. Mutations in the SERT gene are known to correlate with cognitive and behavioral deficits seen in psychiatric disorders, such as anxiety disorders, depression, and autism spectrum disorder. Researchers study these deficits using SERT knockout (KO) mice, a model that lacks functional SERT and displays changes in anxiety, learning, and motivation. We are interested in how the absence of SERT affects visual processing and learning. A popular method of evaluating learning in mice is a touchscreen-based learning paradigm, similar to tests used with both humans and primate models. We have applied this paradigm in our laboratory to study the effect of SERT KO on learning and the visual discrimination of global motion. Mice were first taught to select a visual stimulus for a food reward, then trained to discriminate between left and right coherent dot motion. Our results demonstrate that mice can learn to discriminate between different types of visual stimuli, giving us an experimental platform for future studies of learning and perception in SERT KO mice

Three-dimensional nanoscopy of whole cells and tissues with in situ point spread function retrieval

Single-molecule localization microscopy is a powerful tool for visualizing subcellular structures, interactions and protein functions in biological research. However, inhomogeneous refractive indices inside cells and tissues distort the fluorescent signal emitted from single-molecule probes, which rapidly degrades resolution with increasing depth. We propose a method that enables the construction of an in situ 3D response of single emitters directly from single-molecule blinking datasets, and therefore allows their locations to be pinpointed with precision that achieves the Cramér-Rao lower bound and uncompromised fidelity. We demonstrate this method, named in situ PSF retrieval (INSPR), across a range of cellular and tissue architectures, from mitochondrial networks and nuclear pores in mammalian cells to amyloid-β plaques and dendrites in brain tissues and elastic fibers in developing cartilage of mice. This advancement expands the routine applicability of super-resolution microscopy from selected cellular targets near coverslips to intra- and extracellular targets deep inside tissues

Observation of an Excited Bc+ State

Using pp collision data corresponding to an integrated luminosity of 8.5 fb-1 recorded by the LHCb experiment at center-of-mass energies of s=7, 8, and 13 TeV, the observation of an excited Bc+ state in the Bc+π+π- invariant-mass spectrum is reported. The observed peak has a mass of 6841.2±0.6(stat)±0.1(syst)±0.8(Bc+) MeV/c2, where the last uncertainty is due to the limited knowledge of the Bc+ mass. It is consistent with expectations of the Bc∗(2S31)+ state reconstructed without the low-energy photon from the Bc∗(1S31)+→Bc+γ decay following Bc∗(2S31)+→Bc∗(1S31)+π+π-. A second state is seen with a global (local) statistical significance of 2.2σ (3.2σ) and a mass of 6872.1±1.3(stat)±0.1(syst)±0.8(Bc+) MeV/c2, and is consistent with the Bc(2S10)+ state. These mass measurements are the most precise to date

Study of charmonium production in b -hadron decays and first evidence for the decay Bs0

Using decays to φ-meson pairs, the inclusive production of charmonium states in b-hadron decays is studied with pp collision data corresponding to an integrated luminosity of 3.0 fb−1, collected by the LHCb experiment at centre-of-mass energies of 7 and 8 TeV. Denoting byBC ≡ B(b → C X) × B(C → φφ) the inclusive branching fraction of a b hadron to a charmonium state C that decays into a pair of φ mesons, ratios RC1C2 ≡ BC1 /BC2 are determined as Rχc0ηc(1S) = 0.147 ± 0.023 ± 0.011, Rχc1ηc(1S) =0.073 ± 0.016 ± 0.006, Rχc2ηc(1S) = 0.081 ± 0.013 ± 0.005,Rχc1 χc0 = 0.50 ± 0.11 ± 0.01, Rχc2 χc0 = 0.56 ± 0.10 ± 0.01and Rηc(2S)ηc(1S) = 0.040 ± 0.011 ± 0.004. Here and below the first uncertainties are statistical and the second systematic.Upper limits at 90% confidence level for the inclusive production of X(3872), X(3915) and χc2(2P) states are obtained as RX(3872)χc1 < 0.34, RX(3915)χc0 < 0.12 andRχc2(2P)χc2 < 0.16. Differential cross-sections as a function of transverse momentum are measured for the ηc(1S) andχc states. The branching fraction of the decay B0s → φφφ is measured for the first time, B(B0s → φφφ) = (2.15±0.54±0.28±0.21B)×10−6. Here the third uncertainty is due to the branching fraction of the decay B0s → φφ, which is used for normalization. No evidence for intermediate resonances is seen. A preferentially transverse φ polarization is observed.The measurements allow the determination of the ratio of the branching fractions for the ηc(1S) decays to φφ and p p asB(ηc(1S)→ φφ)/B(ηc(1S)→ p p) = 1.79 ± 0.14 ± 0.32

Bose-Einstein correlations of same-sign charged pions in the forward region in pp collisions at √s=7 TeV

Bose-Einstein correlations of same-sign charged pions, produced in protonproton collisions at a 7 TeV centre-of-mass energy, are studied using a data sample collected by the LHCb experiment. The signature for Bose-Einstein correlations is observed in the form of an enhancement of pairs of like-sign charged pions with small four-momentum difference squared. The charged-particle multiplicity dependence of the Bose-Einstein correlation parameters describing the correlation strength and the size of the emitting source is investigated, determining both the correlation radius and the chaoticity parameter. The measured correlation radius is found to increase as a function of increasing charged-particle multiplicity, while the chaoticity parameter is seen to decreas

Measurement of the inelastic pp cross-section at a centre-of-mass energy of 13TeV

The cross-section for inelastic proton-proton collisions at a centre-of-mass energy of 13TeV is measured with the LHCb detector. The fiducial cross-section for inelastic interactions producing at least one prompt long-lived charged particle with momentum p &gt; 2 GeV/c in the pseudorapidity range 2 &lt; η &lt; 5 is determined to be ϭ acc = 62:2 ± 0:2 ± 2:5mb. The first uncertainty is the intrinsic systematic uncertainty of the measurement, the second is due to the uncertainty on the integrated luminosity. The statistical uncertainty is negligible. Extrapolation to full phase space yields the total inelastic proton-proton cross-section ϭ inel = 75:4 ± 3:0 ± 4:5mb, where the first uncertainty is experimental and the second due to the extrapolation. An updated value of the inelastic cross-section at a centre-of-mass energy of 7TeV is also reported

Updated Determination of D⁰–D¯⁰Mixing and CP Violation Parameters with D⁰→K⁺π⁻ Decays

We report measurements of charm-mixing parameters based on the decay-time-dependent ratio of D⁰→K⁺π⁻ to D⁰→K⁻π⁺ rates. The analysis uses a data sample of proton-proton collisions corresponding to an integrated luminosity of 5.0  fb⁻¹ recorded by the LHCb experiment from 2011 through 2016. Assuming charge-parity (CP) symmetry, the mixing parameters are determined to be x′²=(3.9±2.7)×10⁻⁵, y′=(5.28±0.52)×10⁻³, and R[subscript D]=(3.454±0.031)×10⁻³. Without this assumption, the measurement is performed separately for D⁰ and D[over ¯]⁰ mesons, yielding a direct CP-violating asymmetry A[subscript D]=(-0.1±9.1)×10⁻³, and magnitude of the ratio of mixing parameters 1.00<|q/p|<1.35 at the 68.3% confidence level. All results include statistical and systematic uncertainties and improve significantly upon previous single-measurement determinations. No evidence for CP violation in charm mixing is observed