A5035920743- Neural dynamics and brain function
- Hearing, Cochlea, Tinnitus, Genetics
- Neuroscience and Neuropharmacology Research
- Photoreceptor and optogenetics research
- Hearing Loss and Rehabilitation
- Glioma Diagnosis and Treatment
- Vestibular and auditory disorders
- Bone health and treatments
- Ferroptosis and cancer prognosis
- Bone Metabolism and Diseases
- Bone health and osteoporosis research
- Cell Adhesion Molecules Research
- Ion channel regulation and function
- S100 Proteins and Annexins
- Advanced Electron Microscopy Techniques and Applications
- Caveolin-1 and cellular processes
- Visual perception and processing mechanisms
- Olfactory and Sensory Function Studies
- Osteoarthritis Treatment and Mechanisms
- Exercise and Physiological Responses
- Nanoplatforms for cancer theranostics
- Neurobiology and Insect Physiology Research
- Advanced Memory and Neural Computing
- Neuroscience and Music Perception
- Animal Vocal Communication and Behavior
University of Michigan
2021-2024
Michigan United
2024
University Hospital of Geneva
2002-2024
Oregon Health & Science University
2009-2023
Kresge Eye Institute
2021-2022
Janelia Research Campus
2018
Howard Hughes Medical Institute
2018
Vollum Institute
2014
Intra-tumoral heterogeneity is a hallmark of glioblastoma that challenges treatment efficacy. However, the mechanisms set up tumor and cell migration remain poorly understood. Herein, we present comprehensive spatiotemporal study aligns distinctive intra-tumoral histopathological structures, oncostreams, with dynamic properties specific, actionable, spatial transcriptomic signature. Oncostreams are multicellular fascicles spindle-like aligned cells mesenchymal properties, detected using ex...
Corticofugal projections to evolutionarily ancient, subcortical structures are ubiquitous across mammalian sensory systems. These 'descending' pathways enable the neocortex control ascending representations in a predictive or feedback manner, but underlying cellular mechanisms poorly understood. Here, we combine optogenetic approaches with vivo and vitro patch-clamp electrophysiology study projection from mouse auditory cortex inferior colliculus (IC), major descending pathway that controls...
The inferior colliculus (IC) of the midbrain is important for complex sound processing, such as discriminating conspecific vocalizations and human speech. IC's nonlemniscal, dorsal "shell" region likely this process, neurons in these layers project to higher-order thalamic nuclei that subsequently funnel acoustic signals amygdala nonprimary auditory cortices, forebrain circuits vocalization coding a variety mammals, including humans. However, extent which shell IC transmit features necessary...
The inferior colliculus (IC) is a midbrain hub critical for perceiving complex sounds, such as speech. In addition to processing ascending inputs from most auditory brainstem nuclei, the IC receives descending cortex that control neuron feature selectivity, plasticity, and certain forms of perceptual learning. Although corticofugal synapses primarily release excitatory transmitter glutamate, many physiology studies show cortical activity has net inhibitory effect on spiking. Perplexingly,...
The dorsal cochlear nucleus (DCN) is a cerebellum-like auditory brain stem region whose functions include sound localization and multisensory integration. Although previous in vivo studies have shown that glycinergic GABAergic inhibition regulate the activity of several DCN cell types response to sensory stimuli, data regarding synaptic inputs onto inhibitory interneurons remain limited. Using acute slices from mice, we examined properties excitatory synapses superficial stellate cell,...
The dorsal cochlear nucleus (DCN) integrates auditory and multisensory signals at the earliest levels of processing. Proposed roles for this region include sound localization in vertical plane, head orientation to sounds interest, suppression sensitivity expected sounds. Auditory non-auditory information streams DCN are refined by a remarkably complex array inhibitory excitatory interneurons, role each cell type is gaining increasing attention. One neuron that has been poorly appreciated...
The avian nucleus laminaris (NL) encodes the azimuthal location of low-frequency sound sources by detecting coincidence binaural signals. Accurate detection requires precise developmental regulation lengths fine, bitufted dendrites that characterize neurons in NL. Such has been suggested to be driven local, synaptically mediated, dendritic signals such as Ca(2+). We examined Ca(2+) signaling through patch clamp and ion imaging experiments slices containing from embryonic chicks....
While sclerostin-neutralizing antibodies (Scl-Abs) transiently stimulate bone formation by activating Wnt signaling in osteoblast lineage cells, they exert sustained inhibition of resorption, suggesting an alternate pathway which Scl-Abs control osteoclast activity. Since sclerostin can activate platelet-derived growth factor receptors (PDGFRs) cells vitro and PDGFR these induces resorption through M-CSF secretion, we hypothesized that the prolonged anticatabolic effect could result from...
Sound localization is critical for real-world hearing, such as segregating overlapping sound streams. For optimal flexibility, central representations of auditory space must adapt to peripheral changes in binaural cue availability, following asymmetric hearing loss adulthood. However, whether the mature system can reliably encode spatial upon abrupt input unclear. Here we use 2-photon Ca
Abstract Interleukin (IL)‐4, which exhibits potent anti‐inflammatory activities, is of potential therapeutic value in destructive arthropathies. To further define the response human joint cells to IL‐4, we analyzed ability this cytokine modulate effects IL‐1β and growth factors. Freshly isolated chondrocytes, dedifferentiated synoviocytes were treated with IL‐4 before determination nitric oxide (NO) collagenase production IL‐1β, or proliferation assays presence platelet‐derived factor...
Abstract The inferior colliculus (IC) is a midbrain hub critical for perceiving complex sounds such as speech. In addition to processing ascending inputs from most auditory brainstem nuclei, the IC receives descending cortex that control neuron feature selectivity, plasticity, and certain forms of perceptual learning. Although corticofugal synapses primarily release excitatory transmitter glutamate, many physiology studies show cortical activity has net inhibitory effect on spiking....
Abstract Layer 5 pyramidal neurons of sensory cortices project “corticofugal” axons to myriad sub-cortical targets, thereby broadcasting high-level signals important for perception and learning. Recent studies suggest dendritic Ca 2+ spikes as key biophysical mechanisms supporting corticofugal neuron function: These long-lasting events drive burst firing, initiating uniquely powerful modulate representations trigger learning-related plasticity. However, the behavioral relevance is poorly...
The inferior colliculus (IC) of the midbrain is important for complex sound processing, such as discriminating conspecific vocalizations and human speech. IC's non-lemniscal, dorsal "shell" region likely this process, neurons in these layers project to higher-order thalamic nuclei that subsequently funnel acoustic signals amygdala non-primary auditory cortices; forebrain circuits vocalization coding a variety mammals, including humans. However, extent which shell IC transmit features...
In higher sensory brain regions, slow oscillations (0.5-5 Hz) associated with quiet wakefulness and attention modulate multisensory integration, predictive coding, perception. Although often assumed to originate via thalamocortical mechanisms, the extent which subcortical pathways are independently capable of oscillatory activity is unclear. We find that in first station for auditory processing, cochlear nucleus, fusiform cells from juvenile mice (of either sex) generate robust 1-2 Hz...
ABSTRACT Intra-tumoral heterogeneity and diffuse infiltration are hallmarks of glioblastoma that challenge treatment efficacy. However, the mechanisms set up both tumor invasion remain poorly understood. Herein, we present a comprehensive spatiotemporal study aligns distinctive intra-tumoral histopathological structures, oncostreams, with dynamic properties unique, actionable, spatial transcriptomic signature. Oncostreams multicellular fascicles spindle-like aligned cells mesenchymal...
Abstract Corticofugal projections to evolutionarily ancient, sub-cortical structures are ubiquitous across mammalian sensory systems. These “descending” pathways enable the neocortex control ascending representations in a predictive or feedback manner, but underlying cellular mechanisms poorly understood. Here we combine optogenetic approaches with vivo and vitro patch-clamp electrophysiology study projection from auditory cortex inferior colliculus (IC), major descending pathway that...
Abstract While sclerostin-neutralizing antibodies (Scl-Ab) transiently stimulate bone formation by activating Wnt signaling in osteoblast lineage cells, they exert sustained inhibition of resorption, suggesting an alternate pathway which Scl-Ab control osteoclast activity. Since sclerostin can activate platelet-derived growth factor receptors (PDGFRs) cells vitro and PDGFR these induces resorption through M-CSF secretion, we hypothesized that the prolonged anti-catabolic effect could result...
Abstract XE991 (10,10-bis(4-pyridinylmethyl)-9(10H)-anthracenone) is currently the most widely used and specific antagonist of Kv7 (KCNQ) family K + channels. We report an unexpected antagonistic effect this drug on ionotropic glycine receptors. In recordings synaptic transmission in two brainstem nuclei (the medial nucleus trapezoid body dorsal cochlear nucleus), 10 μM XE991, a concentration typical for studies brain tissue, inhibited evoked glycinergic inhibitory postsynaptic currents...
Abstract Glioblastomas multiforme (GBMs) are the most lethal tumors of brain. Tumoral mesenchymal transformation is a hallmark GBMs associated with alterations in cellular morphology and dynamic organization. However, little known about mechanisms that control this pathological process. Here, we report comprehensive spatiotemporal study integrating novel intra-tumoral histopathological structures, ‘oncostreams’, tumor properties, microenvironment assets spatial molecular features. Cellular...
Abstract Tumor mesenchymal transformation (MT) is a hallmark of high-grade gliomas. The state associated with specific changes related to cell adhesion, migration, and the extracellular matrix. Collagen 1a1 (COL1A1) main component matrix in gliomas, its expression correlates inversely patient survival. However, cellular molecular mechanisms tumor-associated COL1A1 gliomas remains elusive. Our study integrates histopathological features, spatially resolved transcriptomics, dynamics...