Typical development of synaptic and neuronal properties can proceed without microglia in the cortex and thalamus.

Brain-resident macrophages, microglia, have been proposed to have an active role in synaptic refinement and maturation, influencing plasticity and circuit-level connectivity. Here we show that several neurodevelopmental processes previously attributed to microglia can proceed without them. Using a genetically modified mouse that lacks microglia (Csf1r), we find that intrinsic properties, synapse number and synaptic maturation are largely normal in the hippocampal CA1 region and somatosensory cortex at stages where microglia have been implicated.

Genetically modified animals as models of neurodevelopmental conditions: A review of systematic review reporting quality.

Using genetically modified animals to model neurodevelopmental conditions helps better our understanding of biology underlying these conditions. Animal research has unique characteristics not shared with clinical research, meaning systematic review methods must be adapted to this context. We aim to evaluate the quantity, characteristics, and reporting quality of systematic reviews which synthesise research using genetically modified animals to model neurodevelopmental conditions.

Key roles of C2/GAP domains in SYNGAP1-related pathophysiology.

Mutations in SYNGAP1 are a common genetic cause of intellectual disability (ID) and a risk factor for autism. SYNGAP1 encodes a synaptic GTPase-activating protein (GAP) that has both signaling and scaffolding roles. Most pathogenic variants of SYNGAP1 are predicted to result in haploinsufficiency.

A comparison of basal and activity-dependent exon splicing in cortical-patterned neurons of human and mouse origin.

Rodent studies have shown that alternative splicing in neurons plays important roles in development and maturity, and is regulatable by signals such as electrical activity. However, rodent-human similarities are less well explored. We compared basal and activity-dependent exon splicing in cortical-patterned human ESC-derived neurons with that in cortical mouse ESC-derived neurons, primary mouse cortical neurons at two developmental stages, and mouse hippocampal neurons, focussing on conserved orthologous exons.

Transitioning between the EQ-5D youth and adult descriptive systems in a group of adolescents.

Purpose: To investigate whether the same health state results in the same distribution of responses on the EQ-5D youth and adult descriptive systems.

Methods: Adolescents aged 13-18 years with a range of health conditions and from the general school going population were recruited in South Africa (ZA) and Ethiopia (ET). In ZA participants completed the English EQ-5D-3L, EQ-5D-Y-3L and EQ-5D-5L in parallel.

Delayed recruitment of activity-dependent bulk endocytosis in Fmr1 knockout neurons.

The presynapse performs an essential role in brain communication via the activity-dependent release of neurotransmitters. However, the sequence of events through which a presynapse acquires functionality is relatively poorly understood, which is surprising, since mutations in genes essential for its operation are heavily implicated in neurodevelopmental disorders. We addressed this gap in knowledge by determining the developmental trajectory of synaptic vesicle (SV) recycling pathways in primary cultures of rat hippocampal neurons.

Adapting the EQ-5D-3L for adults with mild to moderate learning disabilities.

Background: Approximately 1.5 million adults in the UK have a learning disability. The difference between age at death for this group and the general population is 26 years for females and 22 years for males.

Laboratory Automated Interrogation of Data: an interactive web application for visualization of multilevel data from biological experiments.

A key step in understanding the results of biological experiments is visualization of the data. Many laboratory experiments contain a range of measurements that exist within a hierarchy of interdependence. An automated and facile way to visualize and interrogate such multilevel data, across many experimental variables, would (i) lead to improved understanding of the results, (ii) help to avoid misleading interpretation of statistics and (iii) easily identify outliers and sources of batch and confounding effects.

A Comparison of Items and Constructs of Standardized Health-Related Quality of Life and Mental Well-Being Measures.

Objectives: This study aimed to explore the internal constructs of the concepts being measured by EQ-5D-5L (a health-related quality of life measure that can produce preference-based utility values) and the 12-item General Health Questionnaire (GHQ-12, a mental well-being measure) and to understand to what extent the items of EQ-5D-5L and GHQ-12 associate with each other.

Methods: We used data from 12 701 respondents participating in a Belgian survey in 2022. Correlation coefficients between GHQ-12 and EQ-5D-5L were calculated at both the aggregate and item levels.

Cerebellar contributions to fear-based emotional processing: relevance to understanding the neural circuits involved in autism.

Cerebellar networks have traditionally been linked to sensorimotor control. However, a large body of evidence suggests that cerebellar functions extend to non-motor realms, such as fear-based emotional processing and that these functions are supported by interactions with a wide range of brain structures. Research related to the cerebellar contributions to emotional processing has focussed primarily on the use of well-constrained conditioning paradigms in both human and non-human subjects.

Skin-infiltrating T cells display distinct inflammatory signatures in lichen planus, bullous pemphigoid and pemphigus vulgaris.

Introduction: We here thought to dissect the inflammatory signature in lesions of three skin disorders, which show a common adaptive immune response against autoantigens of the skin but are characterized by diverging clinical phenotypes. Pemphigus vulgaris (PV) and bullous pemphigoid (BP) are type-2-dependent, IgG autoantibody-driven blistering disorders of mucous membranes and skin, which target desmoglein (Dsg)3 and bullous pemphigoid (BP)180, respectively. In contrast, lichen planus (LP) is a common chronic inflammatory disease of the skin and mucous membranes with a pronounced dermal T cell infiltrate.

Astrocytes mediate cell non-autonomous correction of aberrant firing in human FXS neurons.

Pre-clinical studies of fragile X syndrome (FXS) have focused on neurons, with the role of glia remaining largely underexplored. We examined the astrocytic regulation of aberrant firing of FXS neurons derived from human pluripotent stem cells. Human FXS cortical neurons, co-cultured with human FXS astrocytes, fired frequent short-duration spontaneous bursts of action potentials compared with less frequent, longer-duration bursts of control neurons co-cultured with control astrocytes.

COVID-19 and EQ-5D-5L health state valuation.

Background: We investigate whether and how general population health state values were influenced by the initial stages of the COVID-19 pandemic. Changes could have important implications, as general population values are used in health resource allocation.

Data: In Spring 2020, participants in a UK general population survey rated 2 EQ-5D-5L states, 11111 and 55555, as well as dead, using a visual analogue scale (VAS) from 100 = best imaginable health to 0 = worst imaginable health.

Epilepsy-Related CDKL5 Deficiency Slows Synaptic Vesicle Endocytosis in Central Nerve Terminals.

Cyclin-dependent kinase-like 5 (CDKL5) deficiency disorder (CDD) is a severe early-onset epileptic encephalopathy resulting mainly from mutations in the X-linked gene. To determine whether loss of presynaptic CDKL5 function contributes to CDD, we examined synaptic vesicle (SV) recycling in primary hippocampal neurons generated from knockout rat males. Using a genetically encoded reporter, we revealed that CDKL5 is selectively required for efficient SV endocytosis.

Identifying foetal forebrain interneurons as a target for monogenic autism risk factors and the polygenic 16p11.2 microdeletion.

Background: Autism spectrum condition or 'autism' is associated with numerous genetic risk factors including the polygenic 16p11.2 microdeletion. The balance between excitatory and inhibitory neurons in the cerebral cortex is hypothesised to be critical for the aetiology of autism making improved understanding of how risk factors impact on the development of these cells an important area of research.

Abnormal brain state distribution and network connectivity in a rat model.

Mutations in the gene are one of the common predictors of neurodevelopmental disorders, commonly resulting in individuals developing autism, intellectual disability, epilepsy, and sleep deficits. EEG recordings in neurodevelopmental disorders show potential to identify clinically translatable biomarkers to both diagnose and track the progress of novel therapeutic strategies, as well as providing insight into underlying pathological mechanisms. In a rat model of haploinsufficiency in which the exons encoding the calcium/lipid binding and GTPase-activating protein domains have been deleted ( ), we analysed the duration and occurrence of wake, non-rapid eye movement and rapid eye movement brain states during 6 h multi-electrode EEG recordings.

NMDA Receptor C-Terminal Domain Signalling in Development, Maturity, and Disease.

The NMDA receptor is a Ca-permeant glutamate receptor which plays key roles in health and disease. Canonical NMDARs contain two GluN2 subunits, of which 2A and 2B are predominant in the forebrain. Moreover, the relative contribution of 2A vs.

Ca2+ imaging of self and other in medial prefrontal cortex during social dominance interactions in a tube test.

The study of social dominance interactions between animals offers a window onto the decision-making involved in establishing dominance hierarchies and an opportunity to examine changes in social behavior observed in certain neurogenetic disorders. Competitive social interactions, such as in the widely used tube test, reflect this decision-making. Previous studies have focused on the different patterns of behavior seen in the dominant and submissive animal, neural correlates of effortful behavior believed to mediate the outcome of such encounters, and interbrain correlations of neural activity.

Imbalance of flight-freeze responses and their cellular correlates in the Nlgn3 rat model of autism.

Background: Mutations in the postsynaptic transmembrane protein neuroligin-3 are highly correlative with autism spectrum disorders (ASDs) and intellectual disabilities (IDs). Fear learning is well studied in models of these disorders, however differences in fear response behaviours are often overlooked. We aim to examine fear behaviour and its cellular underpinnings in a rat model of ASD/ID lacking Nlgn3.