Sequence learning induces selectivity to multiple task parameters in mouse somatosensory cortex

Sequential temporal ordering and patterning are key features of natural signals, used by the brain to decode stimuli and perceive them as sensory objects. To explore how cortical neuronal activity underpins sequence discrimination, we developed a task in which mice distinguished between tactile “word” sequences constructed from distinct vibrations delivered to the whiskers, assembled in different orders. Animals licked to report the presence of the target sequence. Mice could respond to the earliest possible cues allowing discrimination, effectively solving the task as a “detection of change” problem, but enhanced their performance when responding later. Optogenetic inactivation showed that the somatosensory cortex was necessary for sequence discrimination. Two-photon imaging in layer 2/3 of the primary somatosensory “barrel” cortex (S1bf) revealed that, in well-trained animals, neurons had heterogeneous selectivity to multiple task variables including not just sensory input but also the animal’s action decision and the trial outcome (presence or absence of the predicted reward). Many neurons were activated preceding goal-directed licking, thus reflecting the animal’s learned action in response to the target sequence; these neurons were found as soon as mice learned to associate the rewarded sequence with licking. In contrast, learning evoked smaller changes in sensory response tuning: neurons responding to stimulus features were found in naive mice, and training did not generate neurons with enhanced temporal integration or categorical responses. Therefore, in S1bf, sequence learning results in neurons whose activity reflects the learned association between target sequence and licking rather than a refined representation of sensory features

Effector memory differentiation increases detection of replication-competent HIV-l in resting CD4+ T cells from virally suppressed individuals.

Studies have demonstrated that intensive ART alone is not capable of eradicating HIV-1, as the virus rebounds within a few weeks upon treatment interruption. Viral rebound may be induced from several cellular subsets; however, the majority of proviral DNA has been found in antigen experienced resting CD4+ T cells. To achieve a cure for HIV-1, eradication strategies depend upon both understanding mechanisms that drive HIV-1 persistence as well as sensitive assays to measure the frequency of infected cells after therapeutic interventions. Assays such as the quantitative viral outgrowth assay (QVOA) measure HIV-1 persistence during ART by ex vivo activation of resting CD4+ T cells to induce latency reversal; however, recent studies have shown that only a fraction of replication-competent viruses are inducible by primary mitogen stimulation. Previous studies have shown a correlation between the acquisition of effector memory phenotype and HIV-1 latency reversal in quiescent CD4+ T cell subsets that harbor the reservoir. Here, we apply our mechanistic understanding that differentiation into effector memory CD4+ T cells more effectively promotes HIV-1 latency reversal to significantly improve proviral measurements in the QVOA, termed differentiation QVOA (dQVOA), which reveals a significantly higher frequency of the inducible HIV-1 replication-competent reservoir in resting CD4+ T cells

Reviews

The following publications have been reviewed by the mentioned authors;Getting Things Right Design and Realization by Adrian Marden, reviewed by Michael RobertsVisual Messages: An Introduction to Graphics by C. J. Breckon, L. J. Jones and C. E. Moorhouse, reviewed by John BaleErgonomics in the Computerized Office by Etienne Grandjean, reviewed by T. LawleyTeaching GCSE Craft, Design and Technology by David Rees, reviewed by Brian OppenheimComputers at Work by H. Scott, B. Frost, S. Alexander and G. Bowie, reviewed by S.R. St. J. NeillScience Report for Teachers: 10 Metals at age 15, reviewed by David BarlexThe Anti-Colouring Book by Susan Striker & Edward Kimmel, reviewed by Marshall HughesUnderstanding and Using Technology by A. Todd, C. McRory and D. Todd, reviewed by David Perry

Detection of a Single Identical Cytomegalovirus (CMV) Strain in Recently Seroconverted Young Women

Infection with multiple CMV strains is common in immunocompromised hosts, but its occurrence in normal hosts has not been well-studied.We analyzed CMV strains longitudinally in women who acquired CMV while enrolled in a CMV glycoprotein B (gB) vaccine trial. Sequencing of four variable genes was performed in samples collected from seroconversion and up to 34 months thereafter.199 cultured isolates from 53 women and 65 original fluids from a subset of 19 women were sequenced. 51 women were infected with one strain each without evidence for genetic drift; only two women shed multiple strains. Genetic variability among strains increased with the number of sequenced genetic loci. Nevertheless, 13 of 53 women proved to be infected with an identical CMV strain based on sequencing at all four variable genes. CMV vaccine did not alter the degree of genetic diversity amongst strains.Primary CMV infection in healthy women nearly always involves shedding of one strain that remains stable over time. Immunization with CMVgB-1 vaccine strain is not selective against specific strains. Although 75% of women harbored their unique strain, or a strain shared with only one other woman, 25% shared a single common strain, suggesting that this predominant strain with a particular combination of genetic loci is advantageous in this large urban area

Organization of sensory feature selectivity in the whisker system

Our sensory receptors are faced with an onslaught of different environmental inputs. Each sensory event or encounter with an object involves a distinct combination of physical energy sources impinging upon receptors. In the rodent whisker system, each primary afferent neuron located in the trigeminal ganglion innervates and responds to a single whisker and encodes a distinct set of physical stimulus properties – features – corresponding to changes in whisker angle and shape and the consequent forces acting on the whisker follicle. Here we review the nature of the features encoded by successive stages of processing along the whisker pathway. At each stage different neurons respond to distinct features, such that the population as a whole represents diverse properties. Different neuronal types also have distinct feature selectivity. Thus, neurons at the same stage of processing and responding to the same whisker nevertheless play different roles in representing objects contacted by the whisker. This diversity, combined with the precise timing and high reliability of responses, enables populations at each stage to represent a wide range of stimuli. Cortical neurons respond to more complex stimulus properties – such as correlated motion across whiskers – than those at early subcortical stages. Temporal integration along the pathway is comparatively weak: neurons up to barrel cortex are sensitive mainly to fast (tens of milliseconds) fluctuations in whisker motion. The topographic organization of whisker sensitivity is paralleled by systematic organization of neuronal selectivity to certain other physical features, but selectivity to touch and to dynamic stimulus properties is distributed in “salt-and-pepper” fashion

Small-scale Magnetic Flux Ropes in the First two Parker Solar Probe Encounters

Small-scale magnetic flux ropes (SFRs) are a type of structures in the solar wind that possess helical magnetic field lines. In a recent report (Chen & Hu 2020), we presented the radial variations of the properties of SFR from 0.29 to 8 au using in situ measurements from the Helios, ACE/Wind, Ulysses, and Voyager spacecraft. With the launch of the Parker Solar Probe (PSP), we extend our previous investigation further into the inner heliosphere. We apply a Grad-Shafranov-based algorithm to identify SFRs during the first two PSP encounters. We find that the number of SFRs detected near the Sun is much less than that at larger radial distances, where magnetohydrodynamic (MHD) turbulence may act as the local source to produce these structures. The prevalence of Alfvenic structures significantly suppresses the detection of SFRs at closer distances. We compare the SFR event list with other event identification methods, yielding a dozen well-matched events. The cross-section maps of two selected events confirm the cylindrical magnetic flux rope configuration. The power-law relation between the SFR magnetic field and heliocentric distances seems to hold down to 0.16 au.Comment: Accepted by ApJ on 2020 Sep 1

Magnetic field spectral evolution in the inner heliosphere

Parker Solar Probe and Solar Orbiter data are used to investigate the radial evolution of magnetic turbulence between $0.06 ~ \lesssim R ~\lesssim 1$ au. The spectrum is studied as a function of scale, normalized to the ion inertial scale $d_{i}$. In the vicinity of the Sun, the inertial range is limited to a narrow range of scales and exhibits a power-law exponent of, $\alpha_{B} = -3/2$, independent of plasma parameters. The inertial range grows with distance, progressively extending to larger spatial scales, while steepening towards a $\alpha_{B} =-5/3$ scaling. It is observed that spectra for intervals with large magnetic energy excesses and low Alfv\'enic content steepen significantly with distance, in contrast to highly Alfv\'enic intervals that retain their near-Sun scaling. The occurrence of steeper spectra in slower wind streams may be attributed to the observed positive correlation between solar wind speed and Alfv\'enicity.Comment: Accepted to APJ letters with minor revision

On the Evolution of the Anisotropic Scaling of Magnetohydrodynamic Turbulence in the Inner Heliosphere

We analyze a merged Parker Solar Probe (PSP) and Solar Orbiter (SO) data set covering heliocentric distances 13 R⊙ ≲ R ≲ 220 R⊙ to investigate the radial evolution of power and spectral index anisotropy in the wavevector space of solar wind turbulence. Our results show that anisotropic signatures of turbulence display a distinct radial evolution when fast, Vsw ≥ 400 km s−1, and slow, Vsw ≤ 400 km s−1, wind streams are considered. The anisotropic properties of slow wind in Earth orbit are consistent with a "critically balanced" cascade, but both spectral index anisotropy and power anisotropy diminish with decreasing heliographic distance. Fast streams are observed to roughly retain their near-Sun anisotropic properties, with the observed spectral index and power anisotropies being more consistent with a "dynamically aligned" type of cascade, though the lack of extended fast wind intervals makes it difficult to accurately measure the anisotropic scaling. A high-resolution analysis during the first perihelion of PSP confirms the presence of two subranges within the inertial range, which may be associated with the transition from weak to strong turbulence. The transition occurs at κdi ≈ 6 × 10−2 and signifies a shift from −5/3 to −2 and from −3/2 to −1.57 scaling in parallel and perpendicular spectra, respectively. Our results provide strong observational constraints for anisotropic theories of MHD turbulence in the solar wind