Corticospinal and reticulospinal contacts on cervical commissural and long descending propriospinal neurons in the adult rat spinal cord; evidence for powerful reticulospinal connections

Descending systems have a crucial role in the selection of motor output patterns by influencing the activity of interneuronal networks in the spinal cord. Commissural interneurons that project to the contralateral grey matter are key components of such networks as they coordinate left-right motor activity of fore and hind-limbs. The aim of this study was to determine if corticospinal (CST) and reticulospinal (RST) neurons make significant numbers of axonal contacts with cervical commissural interneurons. Two classes of commissural neurons were analysed: 1) local commissural interneurons (LCINs) in segments C4-5; 2) long descending propriospinal neurons (LDPNs) projecting from C4 to the rostral lumbar cord. Commissural interneurons were labelled with Fluorogold and CST and RST axons were labelled by injecting the b subunit of cholera toxin in the forelimb area of the primary somatosensory cortex or the medial longitudinal fasciculus respectively. The results show that LCINs and LDPNs receive few contacts from CST terminals but large numbers of contacts are formed by RST terminals. Use of vesicular glutamate and vesicular GABA transporters revealed that both types of cell received about 80% excitatory and 20% inhibitory RST contacts. Therefore the CST appears to have a minimal influence on LCINs and LDPNs but the RST has a powerful influence. This suggests that left-right activity in the rat spinal cord is not influenced directly via CST systems but is strongly controlled by the RST pathway. Many RST neurons have monosynaptic input from corticobulbar pathways therefore this pathway may provide an indirect route from the cortex to commissural systems. The cortico-reticulospinal-commissural system may also contribute to functional recovery following damage to the CST as it has the capacity to deliver information from the cortex to the spinal cord in the absence of direct CST input

Longitudinal changes and correlates of meeting WHO recommended levels of physical activity in the UK during the COVID-19 pandemic: Findings from the HEBECO study

BACKGROUND: The COVID-19 pandemic has seen repeated government enforced restrictions on movement. This study aimed to evaluate longitudinal trends in physical activity (PA) in a self-selected UK-based sample and identify the key correlates of these trends. METHODS: From 23 April 2020 to 30 January 2021, measures of PA engagement were collected in a sample of 1,947 UK-based adults. Generalised estimating equations (GEE) explored trends in PA engagement over time, and how sociodemographic, health and contextual factors impacted participant's attainment of World Health Organization (WHO) recommended levels of PA (constituting muscle strengthening activity (MSA), and moderate or vigorous PA (MVPA)). RESULTS: While one in five achieved the recommended levels of PA in the first UK lockdown in April-June 2020 (19.5%, 95%CI: 17.8-21.3%) and a similar proportion in June-July 2020 (17.7%, 95%CI: 16.1-19.5%), this reduced during the period of eased restrictions in August-September 2020 (15.2%, 95%CI: 13.7-16.9%) and the second UK lockdown in November 2020-January 2021 (14.1%, 95%CI: 12.6-15.9%). Similar trends were observed for MSA and MVPA individually. Better quality of life, higher socioeconomic position and pre-COVID-19 PA levels were associated with meeting the WHO recommended levels of PA, while those living with overweight or obesity, a limiting health condition, or isolating showed the inverse associations. Time-specific associations with MSA or MVPA were observed for gender and age. CONCLUSION: Reductions in PA levels throughout the first strict lockdown continued without reversal during the ensuing period. The association of negative change with socioeconomic and health-related indices points towards deepening health inequities during the pandemic

Temporal dissociation of phencyclidine: Induced locomotor and social alterations in rats using an automated homecage monitoring system – implications for the 3Rs and preclinical drug discovery

Background: Rodent behavioural assays are widely used to delineate the mechanisms of psychiatric disorders and predict the efficacy of drug candidates. Conventional behavioural paradigms are restricted to short time windows and involve transferring animals from the homecage to unfamiliar apparatus which induces stress. Additionally, factors including environmental perturbations, handling and the presence of an experimenter can impact behaviour and confound data interpretation. To improve welfare and reproducibility these issues must be resolved. Automated homecage monitoring offers a more ethologically relevant approach with reduced experimenter bias. Aim: To evaluate the effectiveness of an automated homecage system at detecting locomotor and social alterations induced by phencyclidine (PCP) in group-housed rats. PCP is an NMDA receptor antagonist commonly utilised to model aspects of schizophrenia. Methods: Rats housed in groups of 3 were implanted with radio frequency identification (RFID) tags. Each homecage was placed over a RFID reader baseplate for the automated monitoring of the social and locomotor activity of each individual rat. For all rats, we acquired homecage data for 24 h following administration of both saline and PCP (2.5 mg/kg). Results: PCP resulted in significantly increased distance travelled from 15 to 60 min post injection. Furthermore, PCP significantly enhanced time spent isolated from cage-mates and this asociality lasted from 60 to 105 min post treatment. Conclusions: Unlike conventional assays, in-cage monitoring captures the temporal duration of drug effects on multiple behaviours in the same group of animals. This approach could benefit psychiatric preclinical drug discovery though improved welfare and increased between-laboratory replicability

The Use of Predator Proof Fencing as a Management Tool in the Hawaiian Islands: A Case Study of Ka`ena Point Natural Area Reserve

Reports were scanned in black and white at a resolution of 600 dots per inch and were converted to text using Adobe Paper Capture Plug-in.The Ka`ena Point Ecosystem Restoration Project was the result of a partnership between the Hawai`i Department of Land and Natural Resources, Divisions of Forestry and Wildlife and State Parks, the U.S. Fish and Wildlife Service, and the Hawai`i Chapter of The Wildlife Society. Ka`ena Point Natural Area Reserve (NAR) hosts one of the largest seabird colonies in the main Hawaiian islands, three species of endangered plants, and is a pupping ground for the endangered Hawaiian monk seals. Prior to fence construction, nesting seabirds and native plants were under constant threat from predatory animals; up to 15% of seabird chicks were killed each year prior to fledging and many endangered plants were unable to reproduce as a result of seed predation. The project involved the construction of predator-proof fencing (2m tall) to prevent feral predators such as dogs, cats, mongoose, rats and mice from entering into 20ha of coastal habitat within Ka`ena Point, followed by removal of these species

A framework for research into continental ancestry groups of the UK Biobank

BACKGROUND: The UK Biobank is a large prospective cohort, based in the UK, that has deep phenotypic and genomic data on roughly a half a million individuals. Included in this resource are data on approximately 78,000 individuals with “non-white British ancestry.” While most epidemiology studies have focused predominantly on populations of European ancestry, there is an opportunity to contribute to the study of health and disease for a broader segment of the population by making use of the UK Biobank’s “non-white British ancestry” samples. Here, we present an empirical description of the continental ancestry and population structure among the individuals in this UK Biobank subset. RESULTS: Reference populations from the 1000 Genomes Project for Africa, Europe, East Asia, and South Asia were used to estimate ancestry for each individual. Those with at least 80% ancestry in one of these four continental ancestry groups were taken forward (N = 62,484). Principal component and K-means clustering analyses were used to identify and characterize population structure within each ancestry group. Of the approximately 78,000 individuals in the UK Biobank that are of “non-white British” ancestry, 50,685, 6653, 2782, and 2364 individuals were associated to the European, African, South Asian, and East Asian continental ancestry groups, respectively. Each continental ancestry group exhibits prominent population structure that is consistent with self-reported country of birth data and geography. CONCLUSIONS: Methods outlined here provide an avenue to leverage UK Biobank’s deeply phenotyped data allowing researchers to maximize its potential in the study of health and disease in individuals of non-white British ancestry. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s40246-022-00380-5

Drug-responsive autism phenotypes in the 16p11.2 deletion mouse model: a central role for gene-environment interactions

There are no current treatments for autism, despite its high prevalence. Deletions of chromosome 16p11.2 dramatically increase risk for autism, suggesting that mice with an equivalent genetic rearrangement may offer a valuable model for the testing of novel classes of therapeutic drug. 16p11.2 deletion (16p11.2 DEL) mice and wild-type controls were assessed using an ethological approach, with 24 h monitoring of activity and social interaction of groups of mice in a home-cage environment. The ability of the excitation/inhibition modulator N-acetyl cysteine (NAC) and the 5-HT1B/1D/1F receptor agonist eletriptan to normalise the behavioural deficits observed was tested. 16p11.2 DEL mice exhibited largely normal behaviours, but, following the stress of an injection, showed hyperlocomotion, reduced sociability, and a strong anxiolytic phenotype. The hyperactivity and reduced sociability, but not the suppressed anxiety, were effectively attenuated by both NAC and eletriptan. The data suggest that 16p11.2 DEL mice show an autism-relevant phenotype that becomes overt after an acute stressor, emphasising the importance of gene-environmental interactions in phenotypic analysis. Further, they add to an emerging view that NAC, or 5-HT1B/1D/1F receptor agonist treatment, may be a promising strategy for further investigation as a future treatment

Femoral Artery Atherosclerosis Is Associated With Physical Function Across the Spectrum of the Ankle-Brachial Index: The San Diego Population Study.

BackgroundThe ankle-brachial index (ABI) is inadequate to detect early-stage atherosclerotic disease, when interventions to prevent functional decline may be the most effective. We determined associations of femoral artery atherosclerosis with physical functioning, across the spectrum of the ABI, and within the normal ABI range.Methods and resultsIn 2007-2011, 1103 multiethnic men and women participated in the San Diego Population Study, and completed all components of the summary performance score. Using Doppler ultrasound, superficial and common femoral intima media thickness and plaques were ascertained. Logistic regression was used to assess associations of femoral atherosclerosis with the summary performance score and its individual components. Models were adjusted for demographics, lifestyle factors, comorbidities, lipids, and kidney function. In adjusted models, among participants with a normal-range ABI (1.00-1.30), the highest tertile of superficial intima media thickness was associated with lower odds of a perfect summary performance score of 12 (odds ratio=0.56 [0.36, 0.87], P=0.009), and lower odds of a 4-m walk score of 4 (0.34 [0.16, 0.73], P=0.006) and chair rise score of 4 (0.56 [0.34, 0.94], P=0.03). Plaque presence (0.53 [0.29, 0.99], P=0.04) and greater total plaque burden (0.61 [0.43, 0.87], P=0.006) were associated with worse 4-m walk performance in the normal-range ABI group. Higher superficial intima media thickness was associated with lower summary performance score in all individuals (P=0.02).ConclusionsFindings suggest that use of femoral artery atherosclerosis measures may be effective in individuals with a normal-range ABI, especially, for example, those with diabetes mellitus or a family history of peripheral artery disease, when detection can lead to earlier intervention to prevent functional declines and improve quality of life