GPCR signaling gates astrocyte responsiveness to neurotransmitters and control of neuronal activity.

How astrocytes regulate neuronal circuits is a fundamental question in neurobiology. Specifically, how astrocytes respond to different neurotransmitters in vivo and how they affect downstream circuit modulation are questions that remain to be fully elucidated. Here, we report a mechanism in by which G protein-coupled adrenergic signaling in astrocytes can control-or "gate"-their ability to respond to other neurotransmitters.

Defining the molecular identity and morphology of glia limitans superficialis astrocytes in vertebrates.

Astrocytes are a highly abundant glial cell type and perform critical homeostatic functions in the central nervous system. Like neurons, astrocytes have many discrete heterogeneous subtypes. The subtype identity and functions are, at least in part, associated with their anatomical location and can be highly restricted to strategically important anatomical domains.

drives sex differences in age- and Alzheimer's disease-related demyelination.

Alzheimer's disease (AD) and other age-related disorders associated with demyelination exhibit sex differences. In this work, we used single-nuclei transcriptomics to dissect the contributions of sex chromosomes and gonads in demyelination and AD. In a mouse model of demyelination, we identified the roles of sex chromosomes and gonads in modifying microglia and oligodendrocyte responses before and after myelin loss.

Adrenergic signaling gates astrocyte responsiveness to neurotransmitters and control of neuronal activity.

How astrocytes regulate neuronal circuits is a fundamental, unsolved question in neurobiology. Nevertheless, few studies have explored the rules that govern when astrocytes respond to different neurotransmitters and how they affect downstream circuit modulation. Here, we report an unexpected mechanism in by which G-protein coupled adrenergic signaling in astrocytes can control, or "gate," their ability to respond to other neurotransmitters.

Temporal and spatial analysis of astrocytes following stroke identifies novel drivers of reactivity.

Astrocytes undergo robust gene expression changes in response to a variety of perturbations, including ischemic injury. How these transitions are affected by time, and how heterogeneous and spatially distinct various reactive astrocyte populations are, remain unclear. To address these questions, we performed spatial transcriptomics as well as single nucleus RNAseq of ~138,000 mouse forebrain astrocytes at 1, 3, and 14 days after ischemic injury.

Sex Chromosomes and Gonads Shape the Sex-Biased Transcriptomic Landscape in Tlr7-Mediated Demyelination During Aging.

Demyelination occurs in aging and associated diseases, including Alzheimer's disease. Several of these diseases exhibit sex differences in prevalence and severity. Biological sex primarily stems from sex chromosomes and gonads releasing sex hormones.

Defining the molecular identity and morphology of astrocytes in mouse and human.

Astrocytes are a highly abundant glial cell type that perform critical homeostatic functions in the central nervous system. Like neurons, astrocytes have many discrete heterogenous subtypes. The subtype identity and functions are, at least in part, associated with their anatomical location and can be highly restricted to strategically important anatomical domains.

Microglial INPP5D limits plaque formation and glial reactivity in the PSAPP mouse model of Alzheimer's disease.

Introduction: The inositol polyphosphate-5-phosphatase D (INPP5D) gene encodes a dual-specificity phosphatase that can dephosphorylate both phospholipids and phosphoproteins. Single nucleotide polymorphisms in INPP5D impact risk for developing late onset sporadic Alzheimer's disease (LOAD).

Methods: To assess the consequences of inducible Inpp5d knockdown in microglia of APP /PSEN1 (PSAPP) mice, we injected 3-month-old Inpp5d /Cx3cr1 and PSAPP/Inpp5d /Cx3cr1 mice with either tamoxifen (TAM) or corn oil (CO) to induce recombination.

Unique molecular features and cellular responses differentiate two populations of motor cortical layer 5b neurons in a preclinical model of ALS.

Many neurodegenerative diseases, such as amyotrophic lateral sclerosis (ALS), lead to the selective degeneration of discrete cell types in the CNS despite the ubiquitous expression of many genes linked to disease. Therapeutic advancement depends on understanding the unique cellular adaptations that underlie pathology of vulnerable cells in the context of disease-causing mutations. Here, we employ bacTRAP molecular profiling to elucidate cell type-specific molecular responses of cortical upper motor neurons in a preclinical ALS model.

Neuroinflammatory astrocyte subtypes in the mouse brain.

Astrocytes undergo an inflammatory transition after infections, acute injuries and chronic neurodegenerative diseases. How this transition is affected by time and sex, its heterogeneity at the single-cell level and how sub-states are spatially distributed in the brain remains unclear. In this study, we investigated transcriptome changes of mouse cortical astrocytes after an acute inflammatory stimulus using the bacterial cell wall endotoxin lipopolysaccharide.

Astrocyte-immune cell interactions in physiology and pathology.

Astrocytes play both physiological and pathological roles in maintaining central nervous system (CNS) function. Here, we review the varied functions of astrocytes and how these might change in subsets of reactive astrocytes. We review the current understanding of astrocyte interactions with microglia and the vasculature and protective barriers in the central nervous system as well as highlight recent insights into physiologic and reactive astrocyte sub-states identified by transcriptional profiling.

Brain Activity during Methamphetamine Anticipation in a Non-Invasive Self-Administration Paradigm in Mice.

The ability to sense time and anticipate events is critical for survival. Learned responses that allow anticipation of the availability of food or water have been intensively studied. While anticipatory behaviors also occur prior to availability of regularly available rewards, there has been relatively little work on anticipation of drugs of abuse, specifically methamphetamine (MA).