Nicholas Weiler
Communications Manager, Wu Tsai Neurosciences Institute
All Publications
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Synaptic molecular imaging in spared and deprived columns of mouse barrel cortex with array tomography.
Scientific data
2014; 1: 140046-?
Abstract
A major question in neuroscience is how diverse subsets of synaptic connections in neural circuits are affected by experience dependent plasticity to form the basis for behavioral learning and memory. Differences in protein expression patterns at individual synapses could constitute a key to understanding both synaptic diversity and the effects of plasticity at different synapse populations. Our approach to this question leverages the immunohistochemical multiplexing capability of array tomography (ATomo) and the columnar organization of mouse barrel cortex to create a dataset comprising high resolution volumetric images of spared and deprived cortical whisker barrels stained for over a dozen synaptic molecules each. These dataset has been made available through the Open Connectome Project for interactive online viewing, and may also be downloaded for offline analysis using web, Matlab, and other interfaces.
View details for DOI 10.1038/sdata.2014.46
View details for PubMedID 25977797
View details for PubMedCentralID PMC4411012
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Synaptic molecular imaging in spared and deprived columns of mouse barrel cortex with array tomography
SCIENTIFIC DATA
2014; 1
Abstract
A major question in neuroscience is how diverse subsets of synaptic connections in neural circuits are affected by experience dependent plasticity to form the basis for behavioral learning and memory. Differences in protein expression patterns at individual synapses could constitute a key to understanding both synaptic diversity and the effects of plasticity at different synapse populations. Our approach to this question leverages the immunohistochemical multiplexing capability of array tomography (ATomo) and the columnar organization of mouse barrel cortex to create a dataset comprising high resolution volumetric images of spared and deprived cortical whisker barrels stained for over a dozen synaptic molecules each. These dataset has been made available through the Open Connectome Project for interactive online viewing, and may also be downloaded for offline analysis using web, Matlab, and other interfaces.
View details for DOI 10.1038/sdata.2014.46
View details for Web of Science ID 000209843500042
View details for PubMedCentralID PMC4411012
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The Open Connectome Project Data Cluster: Scalable Analysis and Vision for High-Throughput Neuroscience.
Scientific and statistical database management : International Conference, SSDBM ... : proceedings. International Conference on Scientific and Statistical Database Management
2013
Abstract
We describe a scalable database cluster for the spatial analysis and annotation of high-throughput brain imaging data, initially for 3-d electron microscopy image stacks, but for time-series and multi-channel data as well. The system was designed primarily for workloads that build connectomes- neural connectivity maps of the brain-using the parallel execution of computer vision algorithms on high-performance compute clusters. These services and open-science data sets are publicly available at openconnecto.me. The system design inherits much from NoSQL scale-out and data-intensive computing architectures. We distribute data to cluster nodes by partitioning a spatial index. We direct I/O to different systems-reads to parallel disk arrays and writes to solid-state storage-to avoid I/O interference and maximize throughput. All programming interfaces are RESTful Web services, which are simple and stateless, improving scalability and usability. We include a performance evaluation of the production system, highlighting the effec-tiveness of spatial data organization.
View details for PubMedID 24401992
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Deep molecular diversity of mammalian synapses: why it matters and how to measure it
NATURE REVIEWS NEUROSCIENCE
2012; 13 (6): 365-379
Abstract
Pioneering studies in the middle of the twentieth century revealed substantial diversity among mammalian chemical synapses and led to a widely accepted classification of synapse type on the basis of neurotransmitter molecule identity. Subsequently, powerful new physiological, genetic and structural methods have enabled the discovery of much deeper functional and molecular diversity within each traditional neurotransmitter type. Today, this deep diversity continues to pose both daunting challenges and exciting new opportunities for neuroscience. Our growing understanding of deep synapse diversity may transform how we think about and study neural circuit development, structure and function.
View details for DOI 10.1038/nrn3170
View details for Web of Science ID 000304197000007
View details for PubMedID 22573027
View details for PubMedCentralID PMC3670986
- Single-Synapse Analysis of a Diverse Synapse Population: Proteomic Imaging Methods and Markers Neuron 2010; 68: 639-653
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Top-down laminar organization of the excitatory network in motor cortex
NATURE NEUROSCIENCE
2008; 11 (3): 360-366
Abstract
Cortical layering is a hallmark of the mammalian neocortex and a major determinant of local synaptic circuit organization in sensory systems. In motor cortex, the laminar organization of cortical circuits has not been resolved, although their input-output operations are crucial for motor control. Here, we developed a general approach for estimating layer-specific connectivity in cortical circuits and applied it to mouse motor cortex. From these data we computed a laminar presynaptic --> postsynaptic connectivity matrix, W(post,pre), revealing a complement of stereotypic pathways dominated by layer 2 outflow to deeper layers. Network modeling predicted, and experiments with disinhibited slices confirmed, that stimuli targeting upper, but not lower, cortical layers effectively evoked network-wide events. Thus, in motor cortex, descending excitation from a preamplifier-like network of upper-layer neurons drives output neurons in lower layers. Our analysis provides a quantitative wiring-diagram framework for further investigation of the excitatory networks mediating cortical mechanisms of motor control.
View details for DOI 10.1038/nn2049
View details for Web of Science ID 000253548300020
View details for PubMedID 18246064
View details for PubMedCentralID PMC2748826