A5011588237- Neuroinflammation and Neurodegeneration Mechanisms
- Neuroscience and Neuropharmacology Research
- Neurogenesis and neuroplasticity mechanisms
- Adenosine and Purinergic Signaling
- Neuropeptides and Animal Physiology
- Immune cells in cancer
- Pain Mechanisms and Treatments
- Photoreceptor and optogenetics research
- Neurotransmitter Receptor Influence on Behavior
- Epilepsy research and treatment
- Zebrafish Biomedical Research Applications
- Memory and Neural Mechanisms
- Tryptophan and brain disorders
- Anesthesia and Neurotoxicity Research
- Birth, Development, and Health
- Barrier Structure and Function Studies
- Adipose Tissue and Metabolism
- Neurogenetic and Muscular Disorders Research
- Neuroendocrine regulation and behavior
- Chemokine receptors and signaling
- Amyotrophic Lateral Sclerosis Research
- Inflammation biomarkers and pathways
- Attention Deficit Hyperactivity Disorder
- Olfactory and Sensory Function Studies
- Atherosclerosis and Cardiovascular Diseases
Mayo Clinic
2019-2025
WinnMed
2019-2025
Mayo Clinic in Arizona
2019-2025
University of Utah
2014-2016
Spinal long-term potentiation (LTP) at C-fiber synapses is hypothesized to underlie chronic pain. However, a causal link between spinal LTP and pain still lacking. Here, we report that high-frequency stimulation (HFS; 100 Hz, 10 V) of the mouse sciatic nerve reliably induces without causing injury. LTP-inducible triggers lasting for more than 35 days increases number calcitonin gene-related peptide (CGRP) terminals in dorsal horn. The behavioral morphological changes can be prevented by...
Microglial calcium signaling underlies a number of key physiological and pathological processes in situ, but has not been studied vivo awake mice. Using multiple GCaMP6 variants targeted to microglia, we assessed how microglial responds alterations neuronal activity across wide range. We find that only small subset somata exhibited spontaneous transients chronic window preparation. However, hyperactive shifts (kainate status epilepticus CaMKIIa Gq DREADD activation) triggered increased...
The P2Y12 receptor (P2Y12R) is a purinoceptor that selectively expressed in microglia the central nervous system. As signature receptor, microglial P2Y12R mediates process chemotaxis towards ADP/ATP gradients and engaged several neurological diseases including chronic pain, stroke seizures. However, role of regulating neuronal excitability innate behaviors not fully understood. Here, we generated P2Y12-floxed mice to delete beginning development (CX3CR1Cre/+:P2Y12f/f; "constitutive...
Seizures are common in humans with various etiologies ranging from congenital aberrations to acute injuries that alter the normal balance of brain excitation and inhibition. A notable consequence seizures is induction aberrant neurogenesis increased immature neuronal projections. However, regulatory mechanisms governing these features during epilepsy development not fully understood. Recent studies show microglia, brain's resident immune cell, contribute regulate seizure phenotypes. role...
TREM2 is exclusively expressed by microglia in the brain and strongly linked to risk for Alzheimer’s disease (AD). As microglial responses modulated are central AD pathogenesis, enhancing signaling has been explored as an therapeutic strategy. However, effective window targeting unclear. Here, using microglia-specific inducible mouse models overexpressing human wild-type (TREM2-WT) or R47H variant (TREM2-R47H), we show that TREM2-WT expression reduces amyloid deposition neuritic dystrophy...
Spinal microglia are highly responsive to peripheral nerve injury and known be a key player in pain. However, there has not been direct evidence showing that selective microglial activation vivo is sufficient induce chronic Here, we used optogenetic approaches address this question employing CX3CR1 creER/+ : R26 LSL-ReaChR/+ transgenic mice, which red-activated channelrhodopsin (ReaChR) inducibly specifically expressed microglia. We found of ReaChR by red light spinal evoked reliable inward...
Microglia actively survey the brain and dynamically interact with neurons to maintain homeostasis. Microglial Gi protein–coupled receptors (Gi-GPCRs) play a critical role in microglia-neuron communications. However, impact of temporally activating microglial signaling on dynamics neuronal activity homeostatic remains largely unknown. In this study, we used Gi-based designer exclusively activated by drugs (Gi-DREADD) selectively modulate pathway. By integrating chemogenetic approach vivo...
Astrocyte expression of metabotropic glutamate receptor 5 (mGluR5) is consistently observed in resected tissue from patients with epilepsy and equally prevalent animal models epilepsy. However, little known about the functional signaling properties or downstream consequences astrocyte mGluR5 activation during development. In rodent brain, developmentally regulated confined expression/function to first weeks life, similar observations made human control tissue. Herein, we demonstrate that...
Abstract Motor cortical hyperexcitability is well-documented in the presymptomatic stage of amyotrophic lateral sclerosis (ALS). However, mechanisms underlying this early dysregulation are not fully understood. Microglia, as principal immune cells central nervous system, have emerged important players sensing and regulating neuronal activity. Here we investigated role microglia motor circuits a mouse model TDP-43 neurodegeneration (rNLS8). Utilizing multichannel probe recording longitudinal...
SUMMARY Microglial calcium signaling is rare in a baseline state but shows strong engagement during early epilepsy development. The mechanism and purpose behind microglial not known. By developing an vivo UDP fluorescent sensor, GRAB UDP1.0 , we discovered that release conserved response to seizures excitotoxicity across brain regions. signals the P2Y 6 receptor for broad increases epileptogenesis. UDP-P2Y necessary lysosome upregulation limbic regions enhances production of pro-inflammatory...
The discovery of genes encoding the volume-regulated anion channel (VRAC) has enabled detailed exploration its cell type-specific roles in brain. LRRC8A (SWELL1) is essential VRAC subunit. We observed seizure-induced, subunit-specific changes microglial expression and investigated function using conditional knockout (cKO) microglia. SWELL1 cKO mice exhibited a male-specific increase kainate-induced seizure severity yet showed paradoxical neuroprotection against seizure-associated neuronal...
Abstract Microglia actively survey the brain and dynamically interact with neurons to maintain homeostasis. Microglial Gi-protein coupled receptors (Gi-GPCRs) play a critical role in microglia-neuron communications. However, impact of temporally activating microglial Gi signaling on dynamics neuronal activity homeostatic remains largely unknown. In this study, we employed Gi-based Designer Receptors Exclusively Activated by Drugs (Gi-DREADD) selectively modulate pathway. By integrating...
Methylphenidate (MPD) is clinically effective in treating the symptoms of attention-deficit hyperactivity disorder; however, its relatively widespread availability has raised public health concerns on nonmedical use MPD among certain adult populations. Most preclinical studies investigate whether presumed therapeutically relevant doses alter sensitivity to reinforcing effects other drugs, but it remains unclear likely exceeding therapeutic relevance impact subsequent drugs. To begin address...
Abstract Microglia are resident immune cells that dynamically survey the brain parenchyma, interacting with neurons in both health and disease. However, it is still unclear how neuronal network activity drives microglial dynamics. Utilizing vivo two-photon imaging of microglia awake mice, we found inhibition under general anesthesia dramatically increased process surveillance. Accordingly, sensory deprivation optogenetic local mice resulted similar increases We further determined reduced...
Abstract Microglia are resident immune cells of the central nervous system (CNS) and play key roles in brain homeostasis. During anesthesia, microglia increase their dynamic process surveillance interact more closely with neurons. However, functional significance microglial dynamics neuronal interaction has remained unclear. Using vivo two-photon imaging awake mice, we discover that enhance activity after cessation general anesthesia. Hyperactive neuron somata directly contacted by...