Metabotropic signaling within somatostatin interneurons controls transient thalamocortical inputs during development.

During brain development, neural circuits undergo major activity-dependent restructuring. Circuit wiring mainly occurs through synaptic strengthening following the Hebbian "fire together, wire together" precept. However, select connections, essential for circuit development, are transient.

Transgenic Targeting of Creates a Highly Efficient Constitutively Active Microglia Cre Line with Differentiated Specificity.

Microglia carry out important functions as the resident macrophages of the brain. To study their role in health and disease, the research community needs tools to genetically modify them with maximum completeness in a manner that distinguishes them from closely related cell types, such as monocytes. While currently available tamoxifen-inducible CreERT2 lines can achieve the differentiation from other cells, the field needs improved and publicly available constitutively active Cre lines, especially ones with favorable efficiency and specificity profiles for studies where high recombination efficiency is imperative and where tamoxifen administration is contraindicated.

The cumulative impact of trauma, chronic illness, and COVID-19 stress on mental health in a case-control study of adults with psychotic disorders in Ethiopia.

Background: The COVID-19 pandemic has profoundly impacted the economic, psychological, and social well-being of people in Ethiopia. Pandemic-related fears can exacerbate anxiety and depression symptoms among those with pre-existing physical and mental health conditions as well as those with prior exposure to traumatic events.

Methods: We used data from the Ethiopia NeuroGAP-Psychosis study (898 cases and 941 controls with and without a diagnosis of psychosis respectively, 66% male, mean age = 37 years).

Evaluation of polygenic scoring methods in five biobanks shows larger variation between biobanks than methods and finds benefits of ensemble learning.

Methods of estimating polygenic scores (PGSs) from genome-wide association studies are increasingly utilized. However, independent method evaluation is lacking, and method comparisons are often limited. Here, we evaluate polygenic scores derived via seven methods in five biobank studies (totaling about 1.

Single-nucleus sequencing reveals enriched expression of genetic risk factors in extratelencephalic neurons sensitive to degeneration in ALS.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by a progressive loss of motor function linked to degenerating extratelencephalic neurons/Betz cells (ETNs). The reasons why these neurons are selectively affected remain unclear. Here, to understand the unique molecular properties that may sensitize ETNs to ALS, we performed RNA sequencing of 79,169 single nuclei from cortices of patients and controls.

Neocortical inhibitory imbalance predicts successful sensory detection.

Perceptual success depends on fast-spiking, parvalbumin-positive interneurons (FS/PVs). However, competing theories of optimal rate and correlation in pyramidal (PYR) firing make opposing predictions regarding the underlying FS/PV dynamics. We addressed this with population calcium imaging of FS/PVs and putative PYR neurons during threshold detection.

Genomic, molecular, and cellular divergence of the human brain.

While many core biological processes are conserved across species, the human brain has evolved with unique capacities. Current understanding of the neurobiological mechanisms that endow human traits as well as associated vulnerabilities remains limited. However, emerging data have illuminated species divergence in DNA elements and genome organization, in molecular, morphological, and functional features of conserved neural cell types, as well as temporal differences in brain development.

Fluid Biomarkers in Individuals at Risk for Genetic Prion Disease up to Disease Conversion.

Objectives: To longitudinally characterize disease-relevant CSF and plasma biomarkers in individuals at risk for genetic prion disease up to disease conversion.

Methods: This single-center longitudinal cohort study has followed known carriers of pathogenic variants at risk for prion disease, individuals with a close relative who died of genetic prion disease but who have not undergone predictive genetic testing, and controls. All participants were asymptomatic at first visit and returned roughly annually.

Neurogliaform Cells Exhibit Laminar-specific Responses in the Visual Cortex and Modulate Behavioral State-dependent Cortical Activity.

Neurogliaform cells are a distinct type of GABAergic cortical interneurons known for their "volume transmission" output property. However, their activity and function within cortical circuits remain unclear. Here, we developed two genetic tools to target these neurons and examine their function in the primary visual cortex.

Associations between Clinicopathological Characteristics and Intraoperative Opioid Requirements during Endoscopic Submucosal Dissection with Monitored Anesthesia Care: A Retrospective Study.

Endoscopic submucosal dissection is used to treat early gastric neoplasms. Compared with other endoscopic procedures, it requires higher doses of opioids, leading to adverse events during monitored anesthesia care. We investigated the correlations between clinicopathological characteristics and intraprocedural opioid requirements in patients who underwent endoscopic submucosal dissection under monitored anesthesia care.

Three things we learned along the way: lessons for training in psychiatric epidemiology.

The coronavirus disease 2019 (COVID-19) pandemic, and its associated mortality, morbidity, and deep social and economic impacts, was a global traumatic stressor that challenged population mental health and our de facto mental health care system in unprecedented ways. Yet, in many respects, this crisis is not new. Psychiatric epidemiologists have recognized for decades the need and unmet need of people in distress and the limits of the public mental health services in the United States.

Relationships between trauma types and psychotic symptoms: A network analysis of patients with psychotic disorders in a large, multi-country study in East Africa.

Background: The link between trauma exposure and psychotic disorders is well-established. Further, specific types of trauma may be associated with specific psychotic symptoms. Network analysis is an approach that can advance our understanding of the associations across trauma types and psychotic symptoms.

Contribution of copy number variants on antipsychotic treatment response in Han Chinese patients with schizophrenia.

Background: Response to antipsychotic drugs (APD) varies greatly among individuals and is affected by genetic factors. This study aims to demonstrate genome-wide associations between copy number variants (CNVs) and response to APD in patients with schizophrenia.

Methods: A total of 3030 patients of Han Chinese ethnicity randomly received APD (aripiprazole, olanzapine, quetiapine, risperidone, ziprasidone, haloperidol and perphenazine) treatment for six weeks.

A unified framework for estimating country-specific cumulative incidence for 18 diseases stratified by polygenic risk.

Polygenic scores (PGSs) offer the ability to predict genetic risk for complex diseases across the life course; a key benefit over short-term prediction models. To produce risk estimates relevant to clinical and public health decision-making, it is important to account for varying effects due to age and sex. Here, we develop a novel framework to estimate country-, age-, and sex-specific estimates of cumulative incidence stratified by PGS for 18 high-burden diseases.

Conditional knockout of Shank3 in the ventral CA1 by quantitative in vivo genome-editing impairs social memory in mice.

Individuals with autism spectrum disorder (ASD) have a higher prevalence of social memory impairment. A series of our previous studies revealed that hippocampal ventral CA1 (vCA1) neurons possess social memory engram and that the neurophysiological representation of social memory in the vCA1 neurons is disrupted in ASD-associated Shank3 knockout mice. However, whether the dysfunction of Shank3 in vCA1 causes the social memory impairment observed in ASD remains unclear.

Spaceflight induces changes in gene expression profiles linked to insulin and estrogen.

Organismal adaptations to spaceflight have been characterized at the molecular level in model organisms, including Drosophila and C. elegans. Here, we extend molecular work to energy metabolism and sex hormone signaling in mice and humans.

Aging and putative frailty biomarkers are altered by spaceflight.

Human space exploration poses inherent risks to astronauts' health, leading to molecular changes that can significantly impact their well-being. These alterations encompass genomic instability, mitochondrial dysfunction, increased inflammation, homeostatic dysregulation, and various epigenomic changes. Remarkably, these changes bear similarities to those observed during the aging process on Earth.

Spatiotemporal expression and control of haemoglobin in space.

It is now widely recognised that the environment in space activates a diverse set of genes involved in regulating fundamental cellular pathways. This includes the activation of genes associated with blood homoeostasis and erythropoiesis, with a particular emphasis on those involved in globin chain production. Haemoglobin biology provides an intriguing model for studying space omics, as it has been extensively explored at multiple -omic levels, spanning DNA, RNA, and protein analyses, in both experimental and clinical contexts.