A5004920595- Neuroscience and Neuropharmacology Research
- Neural dynamics and brain function
- Photoreceptor and optogenetics research
- Neurogenesis and neuroplasticity mechanisms
- Ion channel regulation and function
- Single-cell and spatial transcriptomics
- Cell Image Analysis Techniques
- Cardiac electrophysiology and arrhythmias
- Neuroscience and Neural Engineering
- Retinal Development and Disorders
- Anesthesia and Neurotoxicity Research
- Neuroinflammation and Neurodegeneration Mechanisms
- Memory and Neural Mechanisms
- Cellular transport and secretion
- Chemical Synthesis and Analysis
- Nicotinic Acetylcholine Receptors Study
- Microfluidic and Bio-sensing Technologies
- Tissue Engineering and Regenerative Medicine
- Sleep and Wakefulness Research
- Amino Acid Enzymes and Metabolism
- Ubiquitin and proteasome pathways
- Receptor Mechanisms and Signaling
- RNA and protein synthesis mechanisms
- Mitochondrial Function and Pathology
- Connexins and lens biology
Allen Institute for Brain Science
2016-2021
Allen Institute
2016-2021
Novartis (United States)
2018
Boston Biomedical Research Institute
2017
Stanford University
2009-2015
Howard Hughes Medical Institute
2009-2011
Harvard University
2003-2009
Harvard University Press
2007
National Institute of Neurological Disorders and Stroke
2003-2006
National Institutes of Health
2003-2006
Each year, 10 million people worldwide survive the neurologic injury associated with a stroke. Importantly, stroke survivors have more than twice risk of subsequently developing dementia compared who never had The link between and later development is not understood. There are reports oligoclonal bands in CSF patients, suggesting that some B-lymphocyte response to may occur CNS. Therefore, we tested hypothesis could contribute onset dementia. We discovered that, mouse models, activated...
This protocol is a practical guide to the N-methyl-D-glucamine (NMDG) protective recovery method of brain slice preparation. Numerous recent studies have validated utility this for enhancing neuronal preservation and overall viability. The implementation technique by early adopters has facilitated detailed investigations into function using diverse experimental applications spanning wide range animal ages, regions, cell types. Steps are outlined carrying out an optimized NMDG artificial...
Synaptic cell adhesion molecules, including the neurexin ligands, neuroligins (NLs) and leucine-rich repeat transmembrane proteins (LRRTMs), are thought to organize synapse assembly specify function. To test synaptic role of these molecules in vivo, we performed lentivirally mediated knockdown NL3, LRRTM1, LRRTM2 CA1 pyramidal cells WT NL1 KO mice at postnatal day (P)0 (when synapses forming) P21 largely mature). P0 NL3 or neurons did not affect excitatory transmission, whereas LRRTM1...
Despite advances in experimental techniques and accumulation of large datasets concerning the composition properties cortex, quantitative modeling cortical circuits under in-vivo-like conditions remains challenging. Here we report publicly release a biophysically detailed circuit model layer 4 mouse primary visual receiving thalamo-cortical inputs. The 45,000-neuron was subjected to battery stimuli, results were compared published work new vivo experiments. Simulations reproduced variety...
Medium spiny neurons (MSNs) are the principal cells of striatum and perform a central role in sensorimotor processing. MSNs must integrate many excitatory inputs located across their dendrites to fire action potentials enable striatal function. However, dependence synaptic responses on temporal spatial distribution these remains unknown. Here, we use whole-cell recordings, two-photon microscopy, glutamate uncaging examine subthreshold integration from acute rat brain slices. We find that can...
Neuroligins (NLs) and leucine-rich repeat transmembrane proteins (LRRTMs) are postsynaptic cell adhesion molecules that bind to presynaptic neurexins. In this paper, we show short hairpin ribonucleic acid–mediated knockdowns (KDs) of LRRTM1, LRRTM2, and/or NL-3, alone or together as double triple KDs (TKDs) in cultured hippocampal neurons, did not decrease synapse numbers. neurons from NL-1 knockout mice, however, TKD LRRTMs NL-3 induced an ∼40% loss excitatory but inhibitory synapses....
Optogenetics provides a unique approach to remotely manipulate brain activity with light. Reaching the degree of spatiotemporal control necessary dissect role individual cells in neuronal networks, some which reside deep brain, requires joint progress opsin engineering and light sculpting methods. Here we investigate for first time two-photon stimulation red-shifted ReaChR. We use (2P) holographic illumination activation individually chosen neurons expressing ReaChR acute slices....
The Patch-seq approach is a powerful variation of the patch-clamp technique that allows for combined electrophysiological, morphological, and transcriptomic characterization individual neurons. To generate datasets at scale, we identified refined key factors contribute to efficient collection high-quality data. We developed electrophysiology software with analysis functions specifically designed automate acquisition online quality control. recognized importance extracting nucleus success...
N-methyl-D-aspartate-receptors (NMDARs) are ionotropic glutamate receptors that function in synaptic transmission, plasticity and cognition. Malfunction of NMDARs has been implicated a variety nervous system disorders, making them attractive therapeutic targets. Overexpression functional NMDAR non-neuronal cells results cell death by excitotoxicity, hindering the development cell-based assays for drug discovery. Here we report plate-based, high-throughput approach to study function. Our...
Long-term depression (LTD) in CA1 pyramidal neurons can be induced by activation of either N-methyl-D-aspartate receptors (NMDARs) or metabotropic glutamate (mGluRs), both which elicit changes synaptic efficacy through alpha-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate receptor (AMPAR) endocytosis. To address the role ubiquitin-proteasome system regulating AMPAR endocytosis during these forms LTD, we examined effects pharmacological inhibitors proteasomal degradation and protein...
This protocol is a practical guide to the N-methyl-D-glucamine (NMDG) protective recovery method of brain slice preparation. Numerous recent studies have validated utility this for enhancing neuronal preservation and overall viability. The implementation technique by early adopters has facilitated detailed investigations into function using diverse experimental applications spanning wide range animal ages, regions, cell types. Steps are outlined carrying out an optimized NMDG artificial...
Unbiased transcriptomic RNA-seq data has provided deep insights into biological processes. However, its impact in drug discovery been narrow given high costs and low throughput. Proof-of-concept studies with Digital RNA pertUrbation of Genes (DRUG)-seq demonstrated the potential to address this gap. We extended DRUG-seq platform by subjecting it rigorous testing adding an open-source analysis pipeline. The results demonstrate reproducibility ability resolve mechanism(s) action for a diverse...
ABSTRACT Understanding the diversity of cell types in brain has been an enduring challenge and requires detailed characterization individual neurons multiple dimensions. To profile morpho-electric properties mammalian systematically, we established a single pipeline using standardized patch clamp recordings slices biocytin-based neuronal reconstructions. We built publicly-accessible online database, Allen Cell Types Database, to display these data sets. Intrinsic physiological morphological...
The Patch-seq approach is a powerful variation of the standard patch clamp technique that allows for combined electrophysiological, morphological, and transcriptomic characterization individual neurons. To generate datasets at scale quality can be integrated with high-throughput dissociated cell data, we have optimized by identifying refining key factors contribute to efficient collection high-quality data. rapidly electrophysiology developed software analysis functions specifically designed...
ABSTRACT Despite advances in experimental techniques and accumulation of large datasets concerning the composition properties cortex, quantitative modeling cortical circuits under in-vivo-like conditions remains challenging. Here we report publicly release a biophysically detailed circuit model layer 4 mouse primary visual receiving thalamo-cortical inputs. The 45,000-neuron was subjected to battery stimuli, results were compared published work new vivo experiments. Simulations reproduced...