Synaptic-like transmission between neural axons and arteriolar smooth muscle cells drives cerebral neurovascular coupling.

Neurovascular coupling (NVC) is important for brain function and its dysfunction underlies many neuropathologies. Although cell-type specificity has been implicated in NVC, how active neural information is conveyed to the targeted arterioles in the brain remains poorly understood. Here, using two-photon focal optogenetics in the mouse cerebral cortex, we demonstrate that single glutamatergic axons dilate their innervating arterioles via synaptic-like transmission between neural-arteriolar smooth muscle cell junctions (NsMJs). The presynaptic parental-daughter bouton makes dual innervations on postsynaptic dendrites and on arteriolar smooth muscle cells (aSMCs), which express many types of neuromediator receptors, including a low level of glutamate NMDA receptor subunit 1 (Grin1). Disruption of NsMJ transmission by aSMC-specific knockout of GluN1 diminished optogenetic and whisker stimulation-caused functional hyperemia. Notably, the absence of GluN1 subunit in aSMCs reduced brain atrophy following cerebral ischemia by preventing Ca2+ overload in aSMCs during arteriolar constriction caused by the ischemia-induced spreading depolarization. Our findings reveal that NsMJ transmission drives NVC and open up a new avenue for studying stroke.

School closures and reopenings during the COVID-19 pandemic: a scoping review protocol.

OBJECTIVE: The objective of this scoping review is to provide an overview of existing studies and evidence on the impact of school closures and reopenings during the pandemic. INTRODUCTION: The COVID-19 pandemic has necessitated widespread school closures, and reopening schools safely has a pivotal role in the well-being of children and teachers, SARS-CoV-2 transmission control and optimal societal functioning. Widespread school closures in response to the COVID-19 pandemic have caused adverse effects on the education, physical health and mental well-being of children. An understanding of the impact of school closures and reopenings as well as factors influencing school safety is critical to bringing schools' operational status back to normal. Despite the implication of individual concerns and knowledge on disease prevention practices, there is a paucity of research on individual knowledge, needs and behaviours in the context of school reopenings. In the proposed study, we will conduct a scoping review to identify and provide inventory of the current research and evidence on the impact of COVID-19 on K-12 schools (primary and secondary schools) and vice versa. METHODS AND ANALYSIS: Eligible studies/literature include members of K-12 (primary and secondary) schools (students, parents, staff, faculty, COVID-19 coordinator, school nurses) in countries affected by the COVID-19 pandemic. We will exclude university or college students. There will be no exclusion based on methods, timing or school operational status.All concepts regarding school closures and reopenings will be considered, and all types of research will be considered.This scoping review will follow the Joanna Briggs Institute methodology for scoping reviews. Sources of evidence published from 2020 to 31 October 2021 will be included. The search will include PubMed, preprints in EuropePMC, ERIC, Scopus, Web of Science Core Collection, PsycINFO, Embase, CINAHL and VHL. We will cover grey literature in Harvard Think Tank Database, COVID-19 Evidence Hub like COVID-END and Google Scholar. The abstract and title screening, full-text screening and data extraction will be done by two independent reviewers.Disagreements will be resolved by an independent third reviewer. Data extract will be done on Qualtrics form to ensure accurate extraction. Citation chaining will be performed on key articles identified. A critical appraisal will be performed.The scoping review will take place from 1 August 2021 to 15 November 2021. We will perform a final round of updated search and citation chaining. ETHICS AND DISSEMINATION: The review will be based on published works and grey literature, thus it is exempt from formal ethical approval. This protocol cannot be registered in the Prospective Register of Systematic Reviews because this registry is not for scoping reviews. We will register it in OSF Registration. The paper will appear in a peer-reviewed, open-access journal to ensure a broad dissemination.