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16 Publications

Showing 1-10 of 16 results
03/11/24 | Spot Spine, a freely available ImageJ plugin for 3D detection and morphological analysis of dendritic spines
Gilles J, Mailly P, Ferreira T, Boudier T, Heck N
F1000Research. 2024 Mar 11;13:. doi: 10.12688/f1000research.146327.1


Dendritic spines are tiny protrusions found along the dendrites of neurons, and their number is a measure of the density of synaptic connections. Altered density and morphology is observed in several pathologies, and spine formation as well as morphological changes correlate with learning and memory. The detection of spines in microscopy images and the analysis of their morphology is therefore a prerequisite for many studies. We have developed a new open-source, freely available, plugin for ImageJ/FIJI, called Spot Spine, that allows detection and morphological measurements of spines in three dimensional images.


Local maxima are detected in spine heads, and the intensity distribution around the local maximum is computed to perform the segmentation of each spine head. Spine necks are then traced from the spine head to the dendrite. Several parameters can be set to optimize detection and segmentation, and manual correction gives further control over the result of the process.


The plugin allows the analysis of images of dendrites obtained with various labeling and imaging methods. Quantitative measurements are retrieved including spine head volume and surface, and neck length.


The plugin and instructions for use are available at

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03/02/23 | Brain-wide neural activity underlying memory-guided movement
Susu Chen , Yi Liu , Ziyue Wang , Jennifer Colonell , Liu D. Liu , Han Hou , Nai-Wen Tien , Tim Wang , Timothy Harris , Shaul Druckmann , Nuo Li , Karel Svoboda
bioRxiv. 2023 Mar 02:. doi: 10.1101/2023.03.01.530520

Behavior requires neural activity across the brain, but most experiments probe neurons in a single area at a time. Here we used multiple Neuropixels probes to record neural activity simultaneously in brain-wide circuits, in mice performing a memory-guided directional licking task. We targeted brain areas that form multi-regional loops with anterior lateral motor cortex (ALM), a key circuit node mediating the behavior. Neurons encoding sensory stimuli, choice, and actions were distributed across the brain. However, in addition to ALM, coding of choice was concentrated in subcortical areas receiving input from ALM, in an ALM-dependent manner. Choice signals were first detected in ALM and the midbrain, followed by the thalamus, and other brain areas. At the time of movement initiation, choice-selective activity collapsed across the brain, followed by new activity patterns driving specific actions. Our experiments provide the foundation for neural circuit models of decision-making and movement initiation.

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Svoboda LabMouseLight
11/12/21 | Accurate localization of linear probe electrodes across multiple brains.
Liu LD, Chen S, Economo MN, Li N, Svoboda K
eNeuro. 2021 Nov 12;8(6):ENEURO.0241-21.2021
04/01/21 | Brain microvasculature has a common topology with local differences in geometry that match metabolic load.
Ji X, Ferreira T, Friedman B, Liu R, Liechty H, Bas E, Chandrashekar J, Kleinfeld D
Neuron. 2021 April 01;109(7):1168. doi: 10.1016/j.neuron.2021.02.006

The microvasculature underlies the supply networks that support neuronal activity within heterogeneous brain regions. What are common versus heterogeneous aspects of the connectivity, density, and orientation of capillary networks? To address this, we imaged, reconstructed, and analyzed the microvasculature connectome in whole adult mice brains with sub-micrometer resolution. Graph analysis revealed common network topology across the brain that leads to a shared structural robustness against the rarefaction of vessels. Geometrical analysis, based on anatomically accurate reconstructions, uncovered a scaling law that links length density, i.e., the length of vessel per volume, with tissue-to-vessel distances. We then derive a formula that connects regional differences in metabolism to differences in length density and, further, predicts a common value of maximum tissue oxygen tension across the brain. Last, the orientation of capillaries is weakly anisotropic with the exception of a few strongly anisotropic regions; this variation can impact the interpretation of fMRI data.

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05/06/20 | Whole-brain profiling of cells and circuits in mammals by tissue clearing and light-sheet microscopy.
Ueda HR, Dodt H, Osten P, Economo MN, Chandrashekar J, Keller PJ
Neuron. 2020 May 06;106(3):369-387. doi: 10.1016/j.neuron.2020.03.004

Tissue clearing and light-sheet microscopy have a 100-year-plus history, yet these fields have been combined only recently to facilitate novel experiments and measurements in neuroscience. Since tissue-clearing methods were first combined with modernized light-sheet microscopy a decade ago, the performance of both technologies has rapidly improved, broadening their applications. Here, we review the state of the art of tissue-clearing methods and light-sheet microscopy and discuss applications of these techniques in profiling cells and circuits in mice. We examine outstanding challenges and future opportunities for expanding these techniques to achieve brain-wide profiling of cells and circuits in primates and humans. Such integration will help provide a systems-level understanding of the physiology and pathology of our central nervous system.

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Dudman LabSternson LabSpruston LabSvoboda LabMouseLight
09/19/19 | Reconstruction of 1,000 projection neurons reveals new cell types and organization of long-range connectivity in the mouse brain.
Winnubst J, Bas E, Ferreira TA, Wu Z, Economo MN, Edson P, Arthur BJ, Bruns C, Rokicki K, Schauder D, Olbris DJ, Murphy SD, Ackerman DG, Arshadi C, Baldwin P, Blake R, Elsayed A, Hasan M, Ramirez D, Dos Santos B, Weldon M, Zafar A, Dudman JT, Gerfen CR, Hantman AW, Korff W, Sternson SM, Spruston N, Svoboda K, Chandrashekar J
Cell. 2019 Sep 19;179(1):268-81. doi: 10.1016/j.cell.2019.07.042

Neuronal 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 constitute more than 85 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.

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09/16/19 | A repeated molecular architecture across thalamic pathways.
Phillips JW, Schulmann A, Hara E, Winnubst J, Liu C, Valakh V, Wang L, Shields BC, Korff W, Chandrashekar J, Lemire AL, Mensh B, Dudman JT, Nelson SB, Hantman AW
Nature Neuroscience. 2019 Sep 16;22(11):1925-35. doi: 10.1038/s41593-019-0483-3

The thalamus is the central communication hub of the forebrain and provides the cerebral cortex with inputs from sensory organs, subcortical systems and the cortex itself. Multiple thalamic regions send convergent information to each cortical region, but the organizational logic of thalamic projections has remained elusive. Through comprehensive transcriptional analyses of retrogradely labeled thalamic neurons in adult mice, we identify three major profiles of thalamic pathways. These profiles exist along a continuum that is repeated across all major projection systems, such as those for vision, motor control and cognition. The largest component of gene expression variation in the mouse thalamus is topographically organized, with features conserved in humans. Transcriptional differences between these thalamic neuronal identities are tied to cellular features that are critical for function, such as axonal morphology and membrane properties. Molecular profiling therefore reveals covariation in the properties of thalamic pathways serving all major input modalities and output targets, thus establishing a molecular framework for understanding the thalamus.

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04/12/19 | Mapping the transcriptional diversity of genetically and anatomically defined cell populations in the mouse brain.
Sugino K, Clark E, Schulmann A, Shima Y, Wang L, Hunt DL, Hooks BM, Traenkner D, Chandrashekar J, Picard S, Lemire AL, Spruston N, Hantman AW, Nelson SB
Elife. 2019 Apr 12;8:. doi: 10.7554/eLife.38619

Understanding the principles governing neuronal diversity is a fundamental goal for neuroscience. Here we provide an anatomical and transcriptomic database of nearly 200 genetically identified cell populations. By separately analyzing the robustness and pattern of expression differences across these cell populations, we identify two gene classes contributing distinctly to neuronal diversity. Short homeobox transcription factors distinguish neuronal populations combinatorially, and exhibit extremely low transcriptional noise, enabling highly robust expression differences. Long neuronal effector genes, such as channels and cell adhesion molecules, contribute disproportionately to neuronal diversity, based on their patterns rather than robustness of expression differences. By linking transcriptional identity to genetic strains and anatomical atlases we provide an extensive resource for further investigation of mouse neuronal cell types.

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Svoboda LabMouseLight
03/12/19 | Single-neuron axonal reconstruction: The search for a wiring diagram of the brain.
Economo MN, Winnubst J, Bas E, Ferreira TA, Chandrashekar J
The Journal of Comparative Neurology. 2019 Mar 12:. doi: 10.1002/cne.24674

Reconstruction of the axonal projection patterns of single neurons has been an important tool for understanding both the diversity of cell types in the brain and the logic of information flow between brain regions. Innovative approaches now enable the complete reconstruction of axonal projection patterns of individual neurons with vastly increased throughput. Here we review how advances in genetic, imaging, and computational techniques have been exploited for axonal reconstruction. We also discuss how new innovations could enable the integration of genetic and physiological information with axonal morphology for producing a census of cell types in the mammalian brain at scale. This article is protected by copyright. All rights reserved.

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Looger LabSvoboda LabMouseLightQuantitative Genomics
10/31/18 | Distinct descending motor cortex pathways and their roles in movement.
Economo MN, Viswanathan S, Tasic B, Bas E, Winnubst J, Menon V, Graybuck LT, Nguyen TN, Smith KA, Yao Z, Wang L, Gerfen CR, Chandrashekar J, Zeng H, Looger LL, Svoboda K
Nature. 2018 Nov;563(7729):79-84. doi: 10.1038/s41586-018-0642-9

Activity in the motor cortex predicts movements, seconds before they are initiated. This preparatory activity has been observed across cortical layers, including in descending pyramidal tract neurons in layer 5. A key question is how preparatory activity is maintained without causing movement, and is ultimately converted to a motor command to trigger appropriate movements. Here, using single-cell transcriptional profiling and axonal reconstructions, we identify two types of pyramidal tract neuron. Both types project to several targets in the basal ganglia and brainstem. One type projects to thalamic regions that connect back to motor cortex; populations of these neurons produced early preparatory activity that persisted until the movement was initiated. The second type projects to motor centres in the medulla and mainly produced late preparatory activity and motor commands. These results indicate that two types of motor cortex output neurons have specialized roles in motor control.

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