A5079254529- Nicotinic Acetylcholine Receptors Study
- Hearing, Cochlea, Tinnitus, Genetics
- Neuroendocrine regulation and behavior
- Photoreceptor and optogenetics research
- Glioma Diagnosis and Treatment
- Neural dynamics and brain function
- Circadian rhythm and melatonin
- Neuroscience and Neuropharmacology Research
- Receptor Mechanisms and Signaling
- MicroRNA in disease regulation
- Neuroinflammation and Neurodegeneration Mechanisms
- interferon and immune responses
- Neurological disorders and treatments
- Single-cell and spatial transcriptomics
- Olfactory and Sensory Function Studies
- Advanced Fluorescence Microscopy Techniques
- Ion Channels and Receptors
- Epigenetics and DNA Methylation
- Cell Image Analysis Techniques
- Immune cells in cancer
- Extracellular vesicles in disease
- Mitochondrial Function and Pathology
- Cholinesterase and Neurodegenerative Diseases
- RNA regulation and disease
- Neurogenesis and neuroplasticity mechanisms
Cold Spring Harbor Laboratory
2012-2023
University Hospital Heidelberg
2021-2023
National Center for Tumor Diseases
2021-2023
Heidelberg University
2021-2023
DKFZ-ZMBH Alliance
2023
Consejo Nacional de Investigaciones Científicas y Técnicas
2005-2018
Tufts University
2007-2009
Experimental Medicine and Biology Institute
2007-2009
University of Buenos Aires
2005-2009
Understanding how brain activation mediates behaviors is a central goal of systems neuroscience. Here, we apply an automated method for mapping in the mouse order to probe sex-specific social are represented male brain. Our uses immediate-early-gene c-fos, marker neuronal activation, visualized by serial two-photon tomography: c-fos-GFP+ neurons computationally detected, their distribution registered reference and atlas, numbers analyzed statistical tests. results reveal distinct shared...
The neuregulin receptor tyrosine kinase Erb-b4, initially linked to early cardiac development, is shown here play a critical role in adult function. In wild-type mice, Erb-b4 protein localized Z lines and intercalated disks, suggesting subcellular intercellular communications of cardiomyocytes. Conditional inactivation erb-b4 ventricular muscle cells led severe dilated cardiomyopathy, characterized by thinned walls with eccentric hypertrophy, reduced contractility, delayed conduction. This...
The transduction of sound in the auditory periphery, cochlea, is inhibited by efferent cholinergic neurons projecting from brainstem and synapsing directly on mechanosensory hair cells. One fundamental question neuroscience what role(s) this feedback plays our ability to hear. In present study, we have engineered a genetically modified mouse model which magnitude duration effects are increased, assess consequences manipulation cochlear function. We generated Chrna9L9'T line knockin mice with...
Although homomeric channels assembled from the alpha9 nicotinic acetylcholine receptor (nAChR) subunit are functional in vitro, electrophysiological, anatomical, and molecular data suggest that native cholinergic olivocochlear function is mediated via heteromeric nAChRs composed of both alpha10 subunits. To gain insight into vivo, we examined olivo cochlear innervation null-mutant mice. Electrophysiological recordings postnatal (P) days P8-9 inner hair cells revealed ACh-gated currents...
The isocitrate dehydrogenase (IDH) gene is recurrently mutated in adult diffuse gliomas. IDH-mutant gliomas are categorized into oligodendrogliomas and astrocytomas, each with unique pathological features. Here, we use single-nucleus RNA ATAC sequencing to compare the molecular heterogeneity of these glioma subtypes. In addition astrocyte-like, oligodendrocyte progenitor-like, cycling tumor subpopulations, a population enriched for ribosomal genes translation elongation factors primarily...
IDH mutant gliomas are grouped into astrocytomas or oligodendrogliomas depending on the codeletion of chromosome arms 1p and 19q. Although genomic alterations have been well described, transcriptional changes unique to either tumor type not fully understood. Here, we identify Tripartite Motif Containing 67 (TRIM67), an E3 ubiquitin ligase with essential roles during neuronal development, as oncogene distinctly upregulated in oligodendrogliomas.We used several cell lines, including...
Abstract Background Glioblastoma (GBM) is an aggressive tumor that frequently exhibits gain of chromosome 7, loss 10, and aberrantly activated receptor tyrosine kinase signaling pathways. Previously, we identified Mesenchyme Homeobox 2 (MEOX2), a gene located on as upregulated transcription factor in GBM. Overexpressed factors can be involved driving Here, aimed to address the role MEOX2 Methods Patient-derived GBM tumorspheres were used constitutively knockdown or overexpress subjected...
In this study, we report the effects of quinoline derivatives quinine, its optical isomer quinidine, and chloroquine on α9α10-containing nicotinic acetylcholine receptors (nAChRs). The compounds blocked (ACh)-evoked responses in α9α10-injected <i>Xenopus laevis</i> oocytes a concentration-dependent manner, with rank order potency (IC<sub>50</sub> = 0.39 μM) > quinine 0.97 ∼ quinidine 1.37 μM). Moreover, ACh-evoked rat cochlear inner hair cells an IC<sub>50</sub> value 0.13 μM, which is...
Abstract Although the synaptogenic program for cholinergic synapses of neuromuscular junction is well known, little known identity or dynamic expression patterns proteins involved in non‐neuromuscular nicotinic synapse development. We have previously demonstrated abnormal presynaptic terminal morphology following loss acetylcholine receptor (nAChR) α9 subunit adult cochleae. However, molecular mechanisms underlying these changes remained obscure. To better understand formation and role...
Gain control of the auditory system operates at multiple levels. Cholinergic medial olivocochlear (MOC) fibers originate in brainstem and make synaptic contacts base outer hair cells (OHCs), final targets several feedback loops from periphery higher-processing centers. Efferent activation inhibits OHC active amplification within mammalian cochlea, through a calcium-permeable α9α10 ionotropic cholinergic nicotinic receptor (nAChR), functionally coupled to calcium activated SK2 potassium...
Significance Vertebrates control the release of urine to mediate physiological functions as well for social communication. The urine, or micturition, is controlled by brain and influenced many internal external factors. In mice, these include standing, sensory context, past experience state bladder. We study circuits that micturition in mice uncover pathways which patterns are altered response changes olfactory stimuli.
Early steps of cancer initiation and metastasis, while critical for understanding disease mechanisms, are difficult to visualize study. Here, we describe an approach study the processes initiation, progression, metastasis prostate (PC) in a genetically engineered RapidCaP mouse model, which combines whole-organ imaging by serial two-photon tomography (STPT) post hoc thick-section immunofluorescent (IF) analysis. STPT enables detection single tumor-initiating cells within entire prostate,...
Abstract The controlled and volitional release of urine, or micturition, serves a fundamental physiological function and, in many species, is critical for social communication. In mice, the decision to urine modulated by external internal factors such as environmental stimuli history transmitted spinal cord via pontine micturition center (PMC). neural pathways which experience sensory interact control PMC activity regulate are unclear. Here we establish behavioral paradigm depending on their...
SUMMARY The thalamic parafascicular nucleus (PF), an excitatory input to the basal ganglia, is targeted with deep-brain-stimulation alleviate a range of neuropsychiatric symptoms. Furthermore, PF lesions disrupt execution correct motor actions in uncertain environments. Nevertheless, circuitry and its contribution action selection are poorly understood. We find that, mice, forms densest subcortical projection striatum. This arises from transcriptionally- physiologically-distinct classes...