scholarly journals Reconstruction of 1,000 Projection Neurons Reveals New Cell Types and Organization of Long-Range Connectivity in the Mouse Brain

2019 ◽  
Author(s):  
Johan Winnubst ◽  
Erhan Bas ◽  
Tiago A. Ferreira ◽  
Zhuhao Wu ◽  
Michael N. Economo ◽  
...  
Keyword(s):  
Long Range ◽  
Mouse Brain ◽  
Cell Types ◽  
Projection Neurons

scholarly journals Reconstruction of 1,000 projection neurons reveals new cell types and organization of long-range connectivity in the mouse brain

2019 ◽  
Author(s):  
Johan Winnubst ◽  
Erhan Bas ◽  
Tiago A. Ferreira ◽  
Zhuhao Wu ◽  
Michael N. Economo ◽  
...  
Keyword(s):  
Long Range ◽  
Mouse Brain ◽  
Neuronal Cell ◽  
Cell Types ◽  
Neuronal Morphology ◽  
Projection Neurons ◽  
Axonal Arbor ◽  
Flow Of Information ◽  
Organizational Principles ◽  
The Brain

SummaryNeuronal cell types are the nodes of neural circuits that determine the flow of information within the brain. Neuronal morphology, especially the shape of the axonal arbor, provides an essential descriptor of cell type and reveals how individual neurons route their output across the brain. Despite the importance of morphology, few projection neurons in the mouse brain have been reconstructed in their entirety. Here we present a robust and efficient platform for imaging and reconstructing complete neuronal morphologies, including axonal arbors that span substantial portions of the brain. We used this platform to reconstruct more than 1,000 projection neurons in the motor cortex, thalamus, subiculum, and hypothalamus. Together, the reconstructed neurons comprise more than 75 meters of axonal length and are available in a searchable online database. Axonal shapes revealed previously unknown subtypes of projection neurons and suggest organizational principles of long-range connectivity.

scholarly journals Reconstruction of 1,000 Projection Neurons Reveals New Cell Types and Organization of Long-Range Connectivity in the Mouse Brain

Cell ◽  
2019 ◽  
Vol 179 (1) ◽  
pp. 268-281.e13 ◽  
Author(s):  
Johan Winnubst ◽  
Erhan Bas ◽  
Tiago A. Ferreira ◽  
Zhuhao Wu ◽  
Michael N. Economo ◽  
...  
Keyword(s):  
Long Range ◽  
Mouse Brain ◽  
Cell Types ◽  
Projection Neurons

scholarly journals A novel population of long-range inhibitory neurons

2019 ◽  
Author(s):  
Zoé Christenson Wick ◽  
Madison R. Tetzlaff ◽  
Esther Krook-Magnuson
Keyword(s):  
Long Range ◽  
Viral Vector ◽  
Neuronal Cell ◽  
Building Blocks ◽  
Cell Types ◽  
Neuronal Population ◽  
Inhibitory Neurons ◽  
Projection Neurons ◽  
Neuronal Diversity ◽  
Rich Diversity

AbstractThe hippocampus, a brain region important for spatial navigation and episodic memory, benefits from a rich diversity of neuronal cell-types. Recent work suggests fundamental gaps in our knowledge of these basic building blocks (i.e., neuronal types) in the hippocampal circuit, despite extensive prior examination. Through the use of an intersectional genetic viral vector approach, we report a novel hippocampal neuronal population, which has not previously been characterized, and which we refer to as LINCs. LINCs are GABAergic, but, in addition to broadly targeting local CA1 cells, also have long-range axons. LINCs are thus both interneurons and projection neurons. We demonstrate that LINCs, despite being relatively few in number, can have a strong influence on both hippocampal and extrahippocampal network synchrony and function. Identification and characterization of this novel cell population advances our basic understanding of both hippocampal circuitry and neuronal diversity.

scholarly journals Mapping Mesoscale Axonal Projections in the Mouse Brain Using A 3D Convolutional Network

2019 ◽  
Author(s):  
Drew Friedmann ◽  
Albert Pun ◽  
Eliza L Adams ◽  
Jan H Lui ◽  
Justus M Kebschull ◽  
...  
Keyword(s):  
Mouse Brain ◽  
Neural Circuit ◽  
Cell Types ◽  
Ease Of Use ◽  
Projection Neurons ◽  
Specific Cell ◽  
Cortical Projection ◽  
Convolutional Network ◽  
Light Sheet Microscopy ◽  
Axonal Projections

AbstractThe projection targets of a neuronal population are a key feature of its anatomical characterization. Historically, tissue sectioning, confocal microscopy, and manual scoring of specific regions of interest have been used to generate coarse summaries of mesoscale projectomes. We present here TrailMap, a 3D convolutional network for extracting axonal projections from intact cleared mouse brains imaged by light-sheet microscopy. TrailMap allows region-based quantification of total axon content in large and complex 3D structures after registration to a standard reference atlas. The identification of axonal structures as thin as one voxel benefits from data augmentation but also requires a loss function that tolerates errors in annotation. A network trained with volumes of serotonergic axons in all major brain regions can be generalized to map and quantify axons from thalamocortical, deep cerebellar, and cortical projection neurons, validating transfer learning as a tool to adapt the model to novel categories of axonal morphology. Speed of training, ease of use, and accuracy improve over existing tools without a need for specialized computing hardware. Given the recent emphasis on genetically and functionally defining cell types in neural circuit analysis, TrailMap will facilitate automated extraction and quantification of axons from these specific cell types at the scale of the entire mouse brain, an essential component of deciphering their connectivity.

scholarly journals Mapping mesoscale axonal projections in the mouse brain using a 3D convolutional network

2020 ◽  
Vol 117 (20) ◽  
pp. 11068-11075 ◽  
Author(s):  
Drew Friedmann ◽  
Albert Pun ◽  
Eliza L. Adams ◽  
Jan H. Lui ◽  
Justus M. Kebschull ◽  
...  
Keyword(s):  
Mouse Brain ◽  
Neural Circuit ◽  
Cell Types ◽  
Ease Of Use ◽  
Projection Neurons ◽  
Specific Cell ◽  
Cortical Projection ◽  
Convolutional Network ◽  
Light Sheet Microscopy ◽  
Axonal Projections

The projection targets of a neuronal population are a key feature of its anatomical characteristics. Historically, tissue sectioning, confocal microscopy, and manual scoring of specific regions of interest have been used to generate coarse summaries of mesoscale projectomes. We present here TrailMap, a three-dimensional (3D) convolutional network for extracting axonal projections from intact cleared mouse brains imaged by light-sheet microscopy. TrailMap allows region-based quantification of total axon content in large and complex 3D structures after registration to a standard reference atlas. The identification of axonal structures as thin as one voxel benefits from data augmentation but also requires a loss function that tolerates errors in annotation. A network trained with volumes of serotonergic axons in all major brain regions can be generalized to map and quantify axons from thalamocortical, deep cerebellar, and cortical projection neurons, validating transfer learning as a tool to adapt the model to novel categories of axonal morphology. Speed of training, ease of use, and accuracy improve over existing tools without a need for specialized computing hardware. Given the recent emphasis on genetically and functionally defining cell types in neural circuit analysis, TrailMap will facilitate automated extraction and quantification of axons from these specific cell types at the scale of the entire mouse brain, an essential component of deciphering their connectivity.

scholarly journals Novel long-range inhibitory nNOS-expressing hippocampal cells

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Zoé Christenson Wick ◽  
Madison R Tetzlaff ◽  
Esther Krook-Magnuson
Keyword(s):  
Long Range ◽  
Hippocampal Neurons ◽  
Viral Vector ◽  
Muscarinic Acetylcholine Receptor ◽  
Neuronal Cell ◽  
Cell Types ◽  
Projection Neurons ◽  
Neuronal Diversity ◽  
Diagonal Band ◽  
Rich Diversity

The hippocampus, a brain region that is important for spatial navigation and episodic memory, benefits from a rich diversity of neuronal cell-types. Through the use of an intersectional genetic viral vector approach in mice, we report novel hippocampal neurons which we refer to as LINCs, as they are long-range inhibitory neuronal nitric oxide synthase (nNOS)-expressing cells. LINCs project to several extrahippocampal regions including the tenia tecta, diagonal band, and retromammillary nucleus, but also broadly target local CA1 cells. LINCs are thus both interneurons and projection neurons. LINCs display regular spiking non-pyramidal firing patterns, are primarily located in the stratum oriens or pyramidale, have sparsely spiny dendrites, and do not typically express somatostatin, VIP, or the muscarinic acetylcholine receptor M2. We further demonstrate that LINCs can strongly influence hippocampal function and oscillations, including interregional coherence. The identification and characterization of these novel cells advances our basic understanding of both hippocampal circuitry and neuronal diversity.

scholarly journals Regulation des Angstverhaltens — zur Rolle neuronaler Netzwerke

BIOspektrum ◽  
2019 ◽  
Vol 25 (7) ◽  
pp. 711-714
Author(s):  
Nina Dedic ◽  
Jan M. Deussing
Keyword(s):  
Stress Response ◽  
Ventral Tegmental Area ◽  
Long Range ◽  
Dopamine Release ◽  
Receptor Type ◽  
Projection Neurons ◽  
Neuronal Circuit ◽  
Brain Reward ◽  
Crh Receptor Type 1

AbstractThe corticotropin-releasing hormone (CRH) system orchestrates the organism’s stress response including the regulation of adaptive be haviours. Here we describe a novel neuronal circuit, which acts anxiety suppressing and positively modulates dopamine release. This anxiolytic circuit comprises inhibitory CRH-expressing, long-range projection neurons within the extended amygdala. These neurons innervate the ventral tegmental area, a prominent brain reward center that expresses high levels of CRH receptor type 1.

scholarly journals Connectivity characterization of the mouse basolateral amygdalar complex

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Houri Hintiryan ◽  
Ian Bowman ◽  
David L. Johnson ◽  
Laura Korobkova ◽  
Muye Zhu ◽  
...  
Keyword(s):  
Granular Cell ◽  
Cell Types ◽  
Projection Neurons ◽  
Cell Type ◽  
Connectivity Map ◽  
Analysis Techniques ◽  
Domain Specific ◽  
Cell Type Specific ◽  
Unique Domain

AbstractThe basolateral amygdalar complex (BLA) is implicated in behaviors ranging from fear acquisition to addiction. Optogenetic methods have enabled the association of circuit-specific functions to uniquely connected BLA cell types. Thus, a systematic and detailed connectivity profile of BLA projection neurons to inform granular, cell type-specific interrogations is warranted. Here, we apply machine-learning based computational and informatics analysis techniques to the results of circuit-tracing experiments to create a foundational, comprehensive BLA connectivity map. The analyses identify three distinct domains within the anterior BLA (BLAa) that house target-specific projection neurons with distinguishable morphological features. We identify brain-wide targets of projection neurons in the three BLAa domains, as well as in the posterior BLA, ventral BLA, posterior basomedial, and lateral amygdalar nuclei. Inputs to each nucleus also are identified via retrograde tracing. The data suggests that connectionally unique, domain-specific BLAa neurons are associated with distinct behavior networks.

scholarly journals HiChIP and Hi-C Protocol Optimized for Primary Murine T Cells

2021 ◽  
Vol 4 (3) ◽  
pp. 49
Author(s):  
Tomas Zelenka ◽  
Charalampos Spilianakis
Keyword(s):  
T Cells ◽  
Long Range ◽  
Three Dimensional ◽  
Cell Types ◽  
Range Interaction ◽  
Chromatin Interactions ◽  
Optimized Protocol ◽  
Long Range Interaction ◽  
Chromatin Compactness ◽  
Detailed Protocol

The functional implications of the three-dimensional genome organization are becoming increasingly recognized. The Hi-C and HiChIP research approaches belong among the most popular choices for probing long-range chromatin interactions. A few methodical protocols have been published so far, yet their reproducibility and efficiency may vary. Most importantly, the high frequency of the dangling ends may dramatically affect the number of usable reads mapped to valid interaction pairs. Additionally, more obstacles arise from the chromatin compactness of certain investigated cell types, such as primary T cells, which due to their small and compact nuclei, impede limitations for their use in various genomic approaches. Here we systematically optimized all the major steps of the HiChIP protocol in T cells. As a result, we reduced the number of dangling ends to nearly zero and increased the proportion of long-range interaction pairs. Moreover, using three different mouse genotypes and multiple biological replicates, we demonstrated the high reproducibility of the optimized protocol. Although our primary goal was to optimize HiChIP, we also successfully applied the optimized steps to Hi-C, given their significant protocol overlap. Overall, we describe the rationale behind every optimization step, followed by a detailed protocol for both HiChIP and Hi-C experiments.

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