Tactile discrimination learning in mice

In order to investigate neuronal activity associated with learning, it is important to use robust behavioural tests that are rapidly acquired, long-lasting and reliant on the sensory modality under investigation. Chapter 1 provides an overview of the whisker-barrel system and currently available behavioural tasks used to assess texture-based learning in mice. A selective review is then presented which highlights the current understanding of synaptic plasticity in the barrel cortex. Chapter 2 reports the findings of a modified novel object recognition task that uses 3-D printed stimuli to assess texture recognition memory. The experiments revealed that mice can retain a memory of tactile stimuli across a 24-hour period, however, the procedure required a large number of animals. Chapter 3 describes the development of a texture-based two-choice discrimination task. The experiments demonstrated that mice can learn rapidly a texture-based discrimination and remember the discrimination over a 24-hour interval. The experiments also revealed that discrimination learning is whisker-dependent: whisker trimming impaired the animals’ ability to learn the texture-discrimination but had no effect on an odour-discrimination. Chapter 4 explored the role of the barrel cortex in the new texture discrimination procedure by reducing the activity of neurons in layer 4 of the barrel cortex using the chemogenetic DREADD technology. The results revealed that reducing activity of these neurons resulted in an inability to acquire the texture discrimination, but did not impair performance on an equivalent odour discrimination task. Analysis of cFos levels, as a proxy for neuronal activity, revealed that in cases infected with DREADDs and activated by CNO, cFos levels were increased in PV cells and decreased in non-PV cells. Together, these experiments suggest a critical role for the barrel cortex in whisker-dependent texture discrimination learning. Chapter 5 explores the broader implications of these results and makes recommendations for future experiments investigating the neural basis of texture discrimination

Perceptual learning with tactile stimuli in rodents: shaping the somatosensory system

The animal kingdom contains species with a wide variety of sensory systems that have been selected to function in different environmental niches, but that are also subject to modification by experience during an organism’s lifetime. The modification of such systems by experience is often called perceptual learning. In rodents, the classic example of perceptual learning is the observation that simple preexposure to two visual stimuli facilitates a subsequent (reinforced) discrimination between them. However, until recently very little behavioral research had investigated perceptual learning with tactile stimuli in rodents, in marked contrast to the wealth of information about plasticity in the rodent somatosensory system. Here we present a selective review of behavioral analyses of perceptual learning with tactile stimuli, alongside evidence concerning the potential bases of such effects within the somatosensory system

Whisker-mediated texture discrimination learning in freely moving mice

Texture is often used as a convenient stimulus dimension to study aspects of discrimination learning in rodents. However, the basis of texture discrimination learning is often left untested: Although learning could involve the whisker system, it could also be based on other senses (e.g., olfactory or visual). Here, we investigated whether mice use their whisker system to learn texture discriminations. Mice were placed in an apparatus illuminated with a dim red light, and the mice had to learn which of 2 sawdust-filled bowls contained a buried reward. The outer surfaces of the bowls were 3−D printed with different textures (grooved or smooth). Within a 60-min session, mice learned to dig in 1 bowl (e.g., grooved) rather than the other (e.g., smooth) to gain the reward. This texture discrimination and an equivalent odor discrimination were retained overnight (Experiments 1 and 2); and whisker trimming disrupted learning based on the texture of the bowls but not learning based on the odor of the sawdust in the bowls (Experiments 3 and 4). These results provide a secure basis upon which to investigate the behavioral and brain basis of texture learning in rodents

Evaluating the risk of SARS-CoV-2 reinfection with the Omicron or Delta variant in Wales, UK

Recent studies suggest an increased risk of reinfection with the SARS-CoV-2 Omicron variant compared with previous variants, potentially due to an increased ability to escape immunity specific to older variants, high antigenic divergence of Omicron from earlier virus variants as well as its altered cell entry pathway. The present study sought to investigate epidemiological evidence for differential SARS-CoV-2 reinfection intervals and incidence rates for the Delta versus Omicron variants within Wales. Reinfections in Wales up to February 2022 were defined using genotyping and whole genome sequencing. The median inter-infection intervals for Delta and Omicron were 226 and 192 days, respectively. An incidence rate ratio of 2.17 for reinfection with Omicron compared to Delta was estimated using a conditional Poisson model, which accounted for several factors including sample collection date, age group, area of residence, vaccination and travel status. These findings are consistent with an increased risk of reinfection with the Omicron variant, and highlight the value of monitoring emerging variants that have the potential for causing further waves of cases

Novel recombinant SARS-CoV-2 lineage detected through genomic surveillance in Wales, UK

Recombination, the process whereby a segment of genetic material from one genome is inserted into another, producing a new chimeric genome, is an important evolutionary mechanism frequently observed in coronaviruses. The risks posed by recombination include the shuffling of advantageous mutations that may increase transmissibility, severity or vaccine escape. We present a genomic and epidemiological description of a new recombinant lineage of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), XR, first identified in Wales. The Pathogen Genomics Unit (Public Health Wales, UK) sequences positive SARS-CoV-2 PCR tests using the ARTIC SARS-CoV-2 sequencing protocol. Recombinants were detected using an in-house pipeline and the epidemiological data analysed in R. Nosocomial cases were defined as those with samples taken after >7 days in hospital. Between February and March 2022, we identified 78 samples with highly similar genomes, comprising a BA.1-like 5' end, a BA.2-like 3' end and a BA.2-like spike protein. This signature is consistent with recombination and was defined as XR by Pangolin (PANGO v1.8). A total of 50 % of cases had a sample collected whilst in hospital and the first three cases were immunocompromised patients. The patient median age was 58 years (range: 4–95 years) and most of the patients were fully vaccinated against SARS-CoV-2 (74 % third dose/booster). Three patients died within 28 days of their sample collection date, one of whom had COVID-19 listed amongst ICD10 (International Classification of Diseases 10) coded causes of death. Our integrated system enabled real-time monitoring of recombinant SARS-CoV-2 for early detection, in order to rapidly risk assess and respond. This work highlights the importance of setting-based surveillance of recombinant SARS-CoV-2, as well as the need to monitor immunocompromised populations through repeat testing and sequencing

Interdependence of primary and secondary somatosensory cortices for plasticity and texture discrimination learning

Feedforward and feedback pathways are important for transfer and integration of information between sensory cortical areas. Here we find that two closely connected cortical areas, the primary (S1) and secondary somatosensory cortices (S2) are both required for mice to learn a whisker-dependent texture discrimination. Increased inhibition in either area (using excitatory DREADDs expressed in inhibitory interneurones) prevents learning. We find that learning the discrimination produces structural plasticity of dendritic spines on layer 2/3 pyramidal neurones in vibrissae S1 that is restricted to the basal dendrites and leaves dendritic spines on apical dendrites unchanged. As S2 projects to the apical dendrites of S1 neurones, we tested whether S2 affects LTP-induction in S1. We found that feedback projections from S2 to S1 gates LTP on feedforward pathways within S1. These studies therefore demonstrate the interdependence of S1 and S2 for learning and plasticity in S1

Epidemiological analysis of the first 1000 cases of SARS-CoV-2 lineage BA.1 (B.1.1.529, Omicron) compared with co-circulating Delta in Wales, UK

Background The Omicron (lineage B.1.1.529) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first reported in Wales, UK, on 3 December 2021. The aim of the study was to describe the first 1000 cases of the Omicron variant by demographic, vaccination status, travel and severe outcome status and compare this to contemporaneous cases of the Delta variant. Methods Testing, typing and contact tracing data were collected by Public Health Wales and analysis undertaken by the Communicable Disease Surveillance Centre (CDSC). Risk ratios for demographic factors and symptoms were calculated comparing Omicron cases to Delta cases identified over the same time period. Results By 14 December 2021, 1000 cases of the Omicron variant had been identified in Wales. Of the first 1000, just 3% of cases had a prior history of travel revealing rapid community transmission. A higher proportion of Omicron cases were identified in individuals aged 20–39, and most cases were double vaccinated (65.9%) or boosted (15.7%). Age-adjusted analysis also revealed that Omicron cases were less likely to be hospitalised (0.4%) or report symptoms (60.8%). Specifically a significant reduction was observed in the proportion of Omicron cases reporting anosmia (8.9%). Conclusion Key findings include a lower risk of anosmia and a reduced risk of hospitalisation in the first 1000 Omicron cases compared with co-circulating Delta cases. We also identify that existing measures for travel restrictions to control importations of new variants identified outside the United Kingdom did not prevent the rapid ingress of Omicron within Wales

A large outbreak of COVID-19 in a UK prison, October 2020 to April 2021

Prisons are susceptible to outbreaks. Control measures focusing on isolation and cohorting negatively affect wellbeing. We present an outbreak of coronavirus disease 2019 (COVID-19) in a large male prison in Wales, UK, October 2020 to April 2021, and discuss control measures. We gathered case-information, including demographics, staff-residence postcode, resident cell number, work areas/dates, test results, staff interview dates/notes and resident prison-transfer dates. Epidemiological curves were mapped by prison location. Control measures included isolation (exclusion from work or cell-isolation), cohorting (new admissions and work-area groups), asymptomatic testing (case-finding), removal of communal dining and movement restrictions. Facemask use and enhanced hygiene were already in place. Whole-genome sequencing (WGS) and interviews determined the genetic relationship between cases plausibility of transmission. Of 453 cases, 53% (n = 242) were staff, most aged 25–34 years (11.5% females, 27.15% males) and symptomatic (64%). Crude attack-rate was higher in staff (29%, 95% CI 26–64%) than in residents (12%, 95% CI 9–15%). Whole-genome sequencing can help differentiate multiple introductions from person-to-person transmission in prisons. It should be introduced alongside asymptomatic testing as soon as possible to control prison outbreaks. Timely epidemiological investigation, including data visualisation, allowed dynamic risk assessment and proportionate control measures, minimising the reduction in resident welfare

Evaluating the effects of SARS-CoV-2 Spike mutation D614G on transmissibility and pathogenicity

SummaryGlobal dispersal and increasing frequency of the SARS-CoV-2 Spike protein variant D614G are suggestive of a selective advantage but may also be due to a random founder effect. We investigate the hypothesis for positive selection of Spike D614G in the United Kingdom using more than 25,000 whole genome SARS-CoV-2 sequences. Despite the availability of a large data set, well represented by both Spike 614 variants, not all approaches showed a conclusive signal of positive selection. Population genetic analysis indicates that 614G increases in frequency relative to 614D in a manner consistent with a selective advantage. We do not find any indication that patients infected with the Spike 614G variant have higher COVID-19 mortality or clinical severity, but 614G is associated with higher viral load and younger age of patients. Significant differences in growth and size of 614G phylogenetic clusters indicate a need for continued study of this variant.</jats:p