scholarly journals Wiring variations that enable and constrain neural computation in a sensory microcircuit

2017 ◽  
Author(s):  
William F. Tobin ◽  
Rachel I. Wilson ◽  
Wei-Chung Allen Lee
Keyword(s):  
Large Scale ◽  
Network Performance ◽  
Olfactory Receptor Neuron ◽  
Neural Computation ◽  
Structural Basis ◽  
Projection Neurons ◽  
Synaptic Connections ◽  
Network Function ◽  
Section Electron ◽  
Serial Section Electron Microscopy

ABSTRACTNeural network function can be shaped by varying the strength of synaptic connections. One way to achieve this is to vary connection structure. To investigate how structural variation among synaptic connections might affect neural computation, we examined primary afferent connections in the Drosophila olfactory system. We used large-scale serial section electron microscopy to reconstruct all the olfactory receptor neuron (ORN) axons that target a left-right pair of glomeruli, as well as all the projection neurons (PNs) postsynaptic to these ORNs. We found three variations in ORN→PN connectivity. First, we found a systematic co-variation in synapse number and PN dendrite size, suggesting total synaptic conductance is tuned to postsynaptic excitability. Second, we discovered that PNs receive more synapses from ipsilateral than contralateral ORNs, providing a structural basis for odor lateralization behavior. Finally, we found evidence of imprecision in ORN→PN connections and show how this can diminish network performance.

scholarly journals Wiring variations that enable and constrain neural computation in a sensory microcircuit

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
William F Tobin ◽  
Rachel I Wilson ◽  
Wei-Chung Allen Lee
Keyword(s):  
Large Scale ◽  
Network Performance ◽  
Olfactory Receptor Neuron ◽  
Neural Computation ◽  
Structural Basis ◽  
Projection Neurons ◽  
Synaptic Connections ◽  
Network Function ◽  
Section Electron ◽  
Serial Section Electron Microscopy

Neural network function can be shaped by varying the strength of synaptic connections. One way to achieve this is to vary connection structure. To investigate how structural variation among synaptic connections might affect neural computation, we examined primary afferent connections in the Drosophila olfactory system. We used large-scale serial section electron microscopy to reconstruct all the olfactory receptor neuron (ORN) axons that target a left-right pair of glomeruli, as well as all the projection neurons (PNs) postsynaptic to these ORNs. We found three variations in ORN→PN connectivity. First, we found a systematic co-variation in synapse number and PN dendrite size, suggesting total synaptic conductance is tuned to postsynaptic excitability. Second, we discovered that PNs receive more synapses from ipsilateral than contralateral ORNs, providing a structural basis for odor lateralization behavior. Finally, we found evidence of imprecision in ORN→PN connections that can diminish network performance.

scholarly journals Synaptic and mitochondrial plasticity associated with fear memory revealed by deep learning-based 3D reconstruction

2021 ◽  
Author(s):  
Jing Liu ◽  
Junqian Qi ◽  
Xi Chen ◽  
Zhenchen Li ◽  
Bei Hong ◽  
...  
Keyword(s):  
Deep Learning ◽  
Fear Conditioning ◽  
Large Scale ◽  
Storage Capacity ◽  
Information Storage ◽  
Cellular Structures ◽  
Neuroscience Research ◽  
Section Electron ◽  
Serial Section Electron Microscopy ◽  
Memory Engram

Reconstruction of serial section electron microscopy (ssEM) data greatly facilitates neuroscience research, but such reconstruction is computationally expensive. Informative data about physiological functions can in theory be obtained from ssEM datasets by extracting distinct cellular structures without large-scale reconstruction, but an efficient method is needed to accomplish this. Here, we developed a Region-CNN (R-CNN) based deep learning method to identify, segment, and reconstruct synapses and mitochondria from ssEM data. We applied this method to explore the changes in synaptic and mitochondrial configuration in the auditory cortex of mice subjected to auditory fear conditioning. Upon reconstructing over 135,000 mitochondria and 160,000 synapses, we found that fear conditioning significantly increases the number while decreasing the size of mitochondria, and also noted that it promoted the formation of multi-contact synapses comprising a single axonal bouton and multiple postsynaptic sites from different dendrites. Combinatorial modeling indicated that such multi-dendritic synapses increased information storage capacity of new synapses by over 50%, representing a synaptic memory engram. Our method achieved high accuracy and speed in synapse and mitochondrion extraction, and its application revealed structural and functional insights about cellular engrams associated with fear conditioning.

scholarly journals A Petascale Automated Imaging Pipeline for Mapping Neuronal Circuits with High-throughput Transmission Electron Microscopy

2019 ◽  
Author(s):  
Wenjing Yin ◽  
Derrick Brittain ◽  
Jay Borseth ◽  
Marie E. Scott ◽  
Derric Williams ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Parallel Imaging ◽  
Large Scale ◽  
Network Connectivity ◽  
Image Capture ◽  
Microscopy Imaging ◽  
Transmission Electron ◽  
Section Electron ◽  
Electron Microscopes ◽  
Serial Section Electron Microscopy

ABSTRACTSerial-section electron microscopy is the method of choice for studying cellular structure and network connectivity in the brain. We have built a pipeline of parallel imaging using transmission electron automated microscopes (piTEAM) that scales this technology and enables the acquisition of petascale datasets containing local cortical microcircuits. The distributed platform is composed of multiple transmission electron microscopes that image, in parallel, different sections from the same block of tissue, all under control of a custom acquisition software (pyTEM) that implements 24/7 continuous autonomous imaging. The suitability of this architecture for large scale electron microscopy imaging was demonstrated by acquiring a volume of more than 1 mm3 of mouse neocortex spanning four different visual areas. Over 26,500 ultrathin tissue sections were imaged, yielding a dataset of more than 2 petabytes. Our current burst imaging rate is 500 Mpixel/s (image capture only) per microscope and net imaging rate is 100 Mpixel/s (including stage movement, image capture, quality control, and post processing). This brings the combined burst acquisition rate of the pipeline to 3 Gpixel/s and the net rate to 600 Mpixel/s with six microscopes running acquisition in parallel, which allowed imaging a cubic millimeter of mouse visual cortex at synaptic resolution in less than 6 months.

scholarly journals An individual interneuron participates in many kinds of inhibition and innervates much of the mouse visual thalamus

2019 ◽  
Author(s):  
Josh L. Morgan ◽  
Jeff W. Lichtman
Keyword(s):  
Inhibitory Interneuron ◽  
Local Processing ◽  
Synaptic Connections ◽  
Diverse Range ◽  
Visual Thalamus ◽  
Section Electron ◽  
Serial Section Electron Microscopy ◽  
Circuit Function ◽  
Global And Local ◽  
Global And Local Processing

SUMMARYOne way to assess a neuron’s function is to describe all its inputs and outputs. With this goal in mind, we used serial section electron microscopy to map 899 synaptic inputs and 623 outputs in one inhibitory interneuron in a large volume of the mouse visual thalamus. This neuron innervated 256 thalamocortical cells spread across functionally distinct subregions of the visual thalamus. All but one of its neurites were bifunctional, innervating thalamocortical and local interneurons while also receiving synapses from the retina. We observed a wide variety of local synaptic motifs. While this neuron innervated many cells weakly, with single en passant synapses, it also deployed specialized branches that climbed along other dendrites to form strong multi-synaptic connections with a subset of partners. This neuron’s diverse range of synaptic relationships allows it to participate in a mix of global and local processing but defies assigning it a single circuit function.

scholarly journals HTPC: heterogeneous traffic-aware partition coding for random packet spraying in data center networks

2021 ◽  
Vol 10 (1) ◽  
Author(s):  
Jiawei Huang ◽  
Shiqi Wang ◽  
Shuping Li ◽  
Shaojun Zou ◽  
Jinbin Hu ◽  
...  
Keyword(s):  
Data Center ◽  
Large Scale ◽  
Network Performance ◽  
Rooted Tree ◽  
Heterogeneous Traffic ◽  
Data Center Networks ◽  
Packet Reordering ◽  
Traffic Characteristics ◽  
Network Utilization ◽  
The Impact

AbstractModern data center networks typically adopt multi-rooted tree topologies such leaf-spine and fat-tree to provide high bisection bandwidth. Load balancing is critical to achieve low latency and high throughput. Although the per-packet schemes such as Random Packet Spraying (RPS) can achieve high network utilization and near-optimal tail latency in symmetric topologies, they are prone to cause significant packet reordering and degrade the network performance. Moreover, some coding-based schemes are proposed to alleviate the problem of packet reordering and loss. Unfortunately, these schemes ignore the traffic characteristics of data center network and cannot achieve good network performance. In this paper, we propose a Heterogeneous Traffic-aware Partition Coding named HTPC to eliminate the impact of packet reordering and improve the performance of short and long flows. HTPC smoothly adjusts the number of redundant packets based on the multi-path congestion information and the traffic characteristics so that the tailing probability of short flows and the timeout probability of long flows can be reduced. Through a series of large-scale NS2 simulations, we demonstrate that HTPC reduces average flow completion time by up to 60% compared with the state-of-the-art mechanisms.

Normal Synaptonemal Complex and Abnormal Recombination Nodules in Two Alleles of the Drosophila Meiotic Mutant mei-W68

Genetics ◽  
2003 ◽  
Vol 163 (4) ◽  
pp. 1337-1356 ◽  
Author(s):  
Adelaide T C Carpenter
Keyword(s):  
Electron Microscopy ◽  
Synaptonemal Complex ◽  
High Frequency ◽  
Serial Section ◽  
The Other ◽  
Wild Type ◽  
Recombination Nodules ◽  
Section Electron ◽  
Serial Section Electron Microscopy ◽  
Section Electron Microscopy

Abstract The meiotic phenotypes of two mutant alleles of the mei-W68 gene, 1 and L1, were studied by genetics and by serial-section electron microscopy. Despite no or reduced exchange, both mutant alleles have normal synaptonemal complex. However, neither has any early recombination nodules; instead, both exhibit high numbers of very long (up to 2 μm) structures here named “noodles.” These are hypothesized to be formed by the unchecked extension of identical but much shorter structures ephemerally seen in wild type, which may be precursors of early recombination nodules. Although the mei-W68L1 allele is identical to the mei-W681 allele in both the absence of early recombination nodules and a high frequency of noodles (i.e., it is amorphic for the noodle phene), it is hypomorphic in its effects on exchange and late recombination nodules. The differential effects of this allele on early and late recombination nodules are consistent with the hypothesis that Drosophila females have two separate recombination pathways—one for simple gene conversion, the other for exchange.

scholarly journals Robust information routing by dorsal subiculum neurons

2021 ◽  
Vol 7 (11) ◽  
pp. eabf1913
Author(s):  
Takuma Kitanishi ◽  
Ryoko Umaba ◽  
Kenji Mizuseki
Keyword(s):  
Nucleus Accumbens ◽  
Large Scale ◽  
Dorsal Hippocampus ◽  
Retrosplenial Cortex ◽  
Projection Neurons ◽  
Target Region ◽  
Ca1 Neurons ◽  
Axonal Projections ◽  
Output Structure ◽  
Hippocampal Ca1

The dorsal hippocampus conveys various information associated with spatial navigation; however, how the information is distributed to multiple downstream areas remains unknown. We investigated this by identifying axonal projections using optogenetics during large-scale recordings from the rat subiculum, the major hippocampal output structure. Subicular neurons demonstrated a noise-resistant representation of place, speed, and trajectory, which was as accurate as or even more accurate than that of hippocampal CA1 neurons. Speed- and trajectory-dependent firings were most prominent in neurons projecting to the retrosplenial cortex and nucleus accumbens, respectively. Place-related firing was uniformly observed in neurons targeting the retrosplenial cortex, nucleus accumbens, anteroventral thalamus, and medial mammillary body. Theta oscillations and sharp-wave/ripples tightly controlled the firing of projection neurons in a target region–specific manner. In conclusion, the dorsal subiculum robustly routes diverse navigation-associated information to downstream areas.

scholarly journals Structural basis for the alternating access mechanism of the cation diffusion facilitator YiiP

2018 ◽  
Vol 115 (12) ◽  
pp. 3042-3047 ◽  
Author(s):  
Maria Luisa Lopez-Redondo ◽  
Nicolas Coudray ◽  
Zhening Zhang ◽  
John Alexopoulos ◽  
David L. Stokes
Keyword(s):  
Large Scale ◽  
Structural Basis ◽  
Membrane Domains ◽  
Cation Diffusion ◽  
Cation Diffusion Facilitator ◽  
X Ray ◽  
Bacterial Membranes ◽  
Helix Bundle ◽  
Four Helix Bundle ◽  
Alternating Access

YiiP is a dimeric antiporter from the cation diffusion facilitator family that uses the proton motive force to transport Zn2+ across bacterial membranes. Previous work defined the atomic structure of an outward-facing conformation, the location of several Zn2+ binding sites, and hydrophobic residues that appear to control access to the transport sites from the cytoplasm. A low-resolution cryo-EM structure revealed changes within the membrane domain that were associated with the alternating access mechanism for transport. In the current work, the resolution of this cryo-EM structure has been extended to 4.1 Å. Comparison with the X-ray structure defines the differences between inward-facing and outward-facing conformations at an atomic level. These differences include rocking and twisting of a four-helix bundle that harbors the Zn2+ transport site and controls its accessibility within each monomer. As previously noted, membrane domains are closely associated in the dimeric structure from cryo-EM but dramatically splayed apart in the X-ray structure. Cysteine crosslinking was used to constrain these membrane domains and to show that this large-scale splaying was not necessary for transport activity. Furthermore, dimer stability was not compromised by mutagenesis of elements in the cytoplasmic domain, suggesting that the extensive interface between membrane domains is a strong determinant of dimerization. As with other secondary transporters, this interface could provide a stable scaffold for movements of the four-helix bundle that confers alternating access of these ions to opposite sides of the membrane.

scholarly journals Relationship-Oriented Software Defined AS-Level Fast Rerouting for Multiple Link Failures

2015 ◽  
Vol 2015 ◽  
pp. 1-15 ◽  
Author(s):  
Chunxiu Li ◽  
Xin Li ◽  
Ke Li ◽  
Jiafu Huang ◽  
Zhansheng Feng ◽  
...  
Keyword(s):  
Distributed Control ◽  
Large Scale ◽  
Network Performance ◽  
Failure Recovery ◽  
Internet Routing ◽  
Link Failures ◽  
Significant Control ◽  
Control Overhead ◽  
Fast Reroute ◽  
Multiple Link Failures

Large-scale deployments of mission-critical services have led to stringent demands on Internet routing, but frequently occurring network failures can dramatically degrade the network performance. However, Border Gateway Protocol (BGP) can not react quickly to recover from them. Although extensive research has been conducted to deal with the problem, the multiple failure scenarios have never been properly addressed due to the limit of distributed control plane. In this paper, we propose a local fast reroute approach to effectively recover from multiple link failures in one administrative domain. The principle of Software Defined Networking (SDN) is used to achieve the software defined AS-level fast rerouting. Considering AS relationships, efficient algorithms are proposed to automatically and dynamically find protection paths for multiple link failures; then OpenFlow forwarding rules are installed on routers to provide data forwarding continuity. Our approach is able to ensure applicability to ASes with flexibility and adaptability to multiple link failures, contributing toward improving the network performance. Through experimental results, we show that our proposal provides effective failure recovery and does not introduce significant control overhead to the network.

The Croonian Lecture, 1970 The structural basis of muscular contraction

1971 ◽  
Vol 178 (1051) ◽  
pp. 131-149 ◽  
Keyword(s):  
Large Scale ◽  
Muscular Contraction ◽  
Important Change ◽  
Structural Basis ◽  
X Ray Diffraction ◽  
New Era ◽  
X Ray ◽  
Biology I ◽  
The Times ◽  
Polypeptide Chains

A previous occasion on which the Croonian lecture was directly concerned with the mechanism of muscular contraction was in 1945, when it was delivered by Professor W. T. Astbury. On that occasion he commented that it was a sign of the times that a physicist should be asked to give the Croonian lecture, and went on to say, and I quote: ‘We are at the dawn of a new era, the era of “molecular biology”, as I like to call it, and there is an urgency about the need for more intensive application of physics and chemistry, and specially structural analysis, to biological problems.’ These were very prophetic words, and, as a physicist just entering biology, I was much interested to read them, and to learn about his experiments. The basic experimental finding which Astbury reported (1947) was that there did not seem to be any important change in the wide angle X-ray diagram from muscle upon contraction; hence it followed that muscles did not contract by any process which simply involved the large-scale disorientation of originally well-ordered polypeptide chains, nor by an alteration in chain configuration in the well-ordered parts of the structure. Astbury suggested instead that there might be ‘specifically active foci’ which one could perhaps paraphrase as ‘larger structural units’ (i.e. larger than individual polypeptide chains) concerned in contraction, which might be studied in the electron microscope or by low angle X-ray diffraction.

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