A5080600710- Neuroscience and Neuropharmacology Research
- Photoreceptor and optogenetics research
- Neural dynamics and brain function
- CRISPR and Genetic Engineering
- Virus-based gene therapy research
- Receptor Mechanisms and Signaling
- Advanced Fluorescence Microscopy Techniques
- RNA and protein synthesis mechanisms
- Neuroscience and Neural Engineering
- bioluminescence and chemiluminescence research
- Retinal Development and Disorders
- Memory and Neural Mechanisms
- Autism Spectrum Disorder Research
- Viral Infectious Diseases and Gene Expression in Insects
- RNA Interference and Gene Delivery
- Genetics and Neurodevelopmental Disorders
- Neuroendocrine regulation and behavior
- Functional Brain Connectivity Studies
- Cholesterol and Lipid Metabolism
- Animal Genetics and Reproduction
- Biotin and Related Studies
- RNA Research and Splicing
- Photochromic and Fluorescence Chemistry
- Neuroscience of respiration and sleep
- Genetics, Bioinformatics, and Biomedical Research
Max Planck Institute for Medical Research
2011-2024
Achucarro Basque Center for Neuroscience
2017-2024
Ikerbasque
2019-2024
Charité - Universitätsmedizin Berlin
2012-2019
Massachusetts Institute of Technology
2014
Max Planck Society
2004-2013
Max Planck Institute of Neurobiology
2007-2008
Heidelberg University
2000
Dartmouth College
1997
University of Göttingen
1972
Regulatory elements that control tetracycline resistance in Escherichia coli were previously converted into highly specific transcription regulation systems function a wide variety of eukaryotic cells. One repressor (TetR) mutant gave rise to rtTA, tetracycline-controlled transactivator requires doxycycline (Dox) for binding tet operators and thus the activation P promoters. Despite intriguing properties its use was limited, particularly transgenic animals, because relatively inefficient...
It is shown that two-photon fluorescence images can be obtained throughout almost the entire gray matter of mouse neocortex by using optically amplified femtosecond pulses. The achieved imaging depth approaches theoretical limit set excitation out-of-focus fluorescence.
We report the cloning of a gene, S2P, that encodes putative metalloprotease required for intramembrane proteolysis sterol-regulatory element–binding proteins (SREBPs) at Site-2. SREBPs are membrane-bound transcription factors activate genes regulating cholesterol metabolism. The active NH2-terminal domains released from membranes by sequential cleavage two sites: Site-1, within lumen endoplasmic reticulum; and Site-2, transmembrane segment. human S2P gene was cloned complementation mutant...
Genetically encoded fluorescent calcium indicator proteins (FCIPs) are promising tools to study dynamics in many activity-dependent molecular and cellular processes. Great hopes-for the measurement of population activity, particular-have therefore been placed on indicators derived from green protein their expression (selected) neuronal populations. Calcium transients can rise within milliseconds, making them suitable as reporters fast activity. We here report production stable transgenic...
Fluorescent calcium (Ca2+) indicator proteins (FCIPs) are promising tools for functional imaging of cellular activity in living animals. However, they have still not reached their full potential vivo neuronal due to limitations expression levels, dynamic range, and sensitivity reporting action potentials. Here, we report that viral the ratiometric Ca2+ sensor yellow cameleon 3.60 (YC3.60) pyramidal neurons mouse barrel cortex enables measurement with high range across multiple spatial...
A method allowing for efficient and quantitative coexpression of multiple heterologous proteins in neurons vivo would be highly valuable many applications neuroscience. To date, different approaches, such as internal ribosomal entry site (IRES) elements ([Douin et al., 2004][1]),
Abstract NMDA receptor-dependent long-term depression (LTD) in the hippocampus is a well-known form of synaptic plasticity that has been linked to different cognitive functions. The core mechanism for this thought be entirely neuronal. However, we now demonstrate astrocytic activity drives LTD at CA3-CA1 synapses. We have found induction enhances astrocyte-to-neuron communication mediated by glutamate, and Ca 2+ signaling SNARE-dependent vesicular release from astrocyte are required...
To identify the underlying reason for controversial performance of tetracycline (Tet)-controlled regulated gene expression in mammalian neurons, we investigated each three components that comprise Tet inducible systems, namely tetracyclines as inducers, tetracycline-transactivator (tTA) and reverse tTA (rtTA), tTA-responsive promoters (P(tets)). We have discovered stably integrated P(tet) becomes functionally silenced majority neurons when it is inactive during development. silencing can be...
The circadian pacemaker in the hypothalamic suprachiasmatic nucleus (SCN) is a hierarchical multioscillator system which neuronal networks play crucial roles expressing coherent rhythms physiology and behavior. However, our understanding of network still incomplete. Intracellular calcium mediates input signals, such as phase-resetting stimuli, to core molecular loop involving clock genes for rhythm generation output signals from various cellular functions, including changes neurotransmitter...
The primary motor cortex has an important role in the precise execution of learned responses. During learning, synaptic efficacy between sensory and cortical neurons is enhanced, possibly involving long-term potentiation N-methyl-D-aspartate (NMDA)-specific glutamate receptor function. To investigate whether NMDA can act as a coincidence detector for activity-dependent changes strength associative here we generate mice with deletion Grin1 gene, encoding essential subunit 1 (GluN1),...
Both genetic inactivation and pharmacological inhibition of the cholesteryl ester synthetic enzyme acyl-CoA:cholesterol acyltransferase 1 (ACAT1) have shown benefit in mouse models Alzheimer's disease (AD). In this study, we aimed to test potential therapeutic applications adeno-associated virus (AAV)-mediated Acat1 gene knockdown AD mice. We constructed recombinant AAVs expressing artificial microRNA (miRNA) sequences, which targeted for knockdown. demonstrated that our could infect...
There is little consensus and controversial evidence on anatomical alterations in the brains of people with autism spectrum disorder (ASD), due part to large heterogeneity present ASD, which turn a major drawback for developing therapies. One strategy characterize this ASD cluster large-scale functional brain connectivity profiles.A subtyping approach based clustering patterns was applied population 657 autistic individuals quality-assured neuroimaging data. We then used high-resolution gene...
Abstract It is assumed that the claustrum (CL) involved in sensorimotor integration and cognitive processes. We recorded firing activity of identified CL neurons during classical eyeblink conditioning rabbits, using a delay paradigm which tone was presented as conditioned stimulus (CS), followed by corneal air puff unconditioned (US). Neurons were their activation from motor (MC), cingulate (CC), medial prefrontal (mPFC) cortices. rarely activated single stimuli any modality. In contrast,...
The hippocampus is crucial for acquiring and retrieving episodic contextual memories. In previous studies, the inactivation of dentate gyrus (DG) neurons by chemogenetic- optogenetic-mediated hyperpolarization led to opposing conclusions about DG's role in memory retrieval. One study used Designer Receptors Exclusively Activated Drugs (DREADD)-mediated clozapine N-oxide (CNO)-induced reported that previously formed was erased, thus concluding denate needed maintenance. other optogenetic with...
Rett syndrome caused by MeCP2 mutations is a devastating neurodevelopmental disorder accompanied severe breathing irregularities. Using transduction of organotypic slices from model MeCP2-/y mice with neuron-specific calcium sensor protein D3cpv, we examined the slow buffering in neurons pre-Bötzinger complex (preBötC), component respiratory network. Examination wild-type (WT) and null showed clear differences spatial organisations preBötC also disturbances homeostasis mutant during early...
Post-traumatic stress disorder (PTSD) is a psychiatric whose pathogenesis relies on maladaptive expression of the memory for life-threatening experience, characterized by over-consolidation, generalization, and impaired extinction, which are responsible dramatic changes in arousal, mood, anxiety, social behavior. Even if subjects experiencing traumatic event during lifetime all show an acute response to trauma, only subset them (susceptible) ultimately develops PTSD, meanwhile others...