SNT: a unifying toolbox for quantification of neuronal anatomy

Arshadi, Cameron; Günther, Ulrik; Eddison, Mark; Harrington, Kyle; Ferreira, Tiago Alves

doi:10.1038/s41592-021-01105-7

Cited by 222 publications

(159 citation statements)

References 62 publications

(77 reference statements)

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“…For analysis of fluorescence intensity, images were acquired at 16bit depth. For neural tracing and morphological reconstruction, stacks were acquired at 1 µm step size and the SNT 3.1.109 tool of Fiji/ImageJ was employed (Arshadi et al, 2021).…”

Section: Immunohistochemistry and Imaging Analysismentioning

confidence: 99%

Developmental Disruption of Erbb4 in Pet1+ Neurons Impairs Serotonergic Sub-System Connectivity and Memory Formation

Barettino

Ballesteros-Gonzalez

Aylón

et al. 2021

Front. Cell Dev. Biol.

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The serotonergic system of mammals innervates virtually all the central nervous system and regulates a broad spectrum of behavioral and physiological functions. In mammals, serotonergic neurons located in the rostral raphe nuclei encompass diverse sub-systems characterized by specific circuitry and functional features. Substantial evidence suggest that functional diversity of serotonergic circuits has a molecular and connectivity basis. However, the landscape of intrinsic developmental mechanisms guiding the formation of serotonergic sub-systems is unclear. Here, we employed developmental disruption of gene expression specific to serotonergic subsets to probe the contribution of the tyrosine kinase receptor ErbB4 to serotonergic circuit formation and function. Through an in vivo loss-of-function approach, we found that ErbB4 expression occurring in a subset of serotonergic neurons, is necessary for axonal arborization of defined long-range projections to the forebrain but is dispensable for the innervation of other targets of the serotonergic system. We also found that Erbb4-deletion does not change the global excitability or the number of neurons with serotonin content in the dorsal raphe nuclei. In addition, ErbB4-deficiency in serotonergic neurons leads to specific behavioral deficits in memory processing that involve aversive or social components. Altogether, our work unveils a developmental mechanism intrinsically acting through ErbB4 in subsets of serotonergic neurons to orchestrate a precise long-range circuit and ultimately involved in the formation of emotional and social memories.

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Section: Immunohistochemistry and Imaging Analysismentioning

confidence: 99%

Developmental Disruption of Erbb4 in Pet1+ Neurons Impairs Serotonergic Sub-System Connectivity and Memory Formation

Barettino

Ballesteros-Gonzalez

Aylón

et al. 2021

Front. Cell Dev. Biol.

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“…ImageJ's Simple Neurite Tracer plugin 42,43 was used to trace, in a semi-automated way, every α-SMA+ vessel that originated downstream of the LCA occlusion (suture) and connected to either the RCA, SpA, or the LCA upstream of the occlusion. Traced paths were isolated and masked so that 3D rendering in Imaris created a map of every collateral artery found post-MI (Fig.…”

Section: Imaging the Entire Coronary Artery Tree In Neonate And Adult Mouse Heartsmentioning

confidence: 99%

“…The resulting image stack was used as a 3D outline of the arterial structure as the foundation for further modeling and analysis. After discontinuation of Simple Neurite Tracer, the updated version SNT was used in similar manner as above 42 .…”

Section: Semi-automated Artery Tracingmentioning

confidence: 99%

Blood flow modeling reveals improved collateral artery performance during mammalian heart regeneration

Anbazhakan

Coronado

Sy-Quia

et al. 2021

Preprint

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Collateral arteries are a vessel subtype that bridges two artery branches, forming a natural bypass that can deliver blood flow downstream of an occlusion. These bridges in the human heart are associated with better outcomes during coronary artery disease. We recently found that their rapid development in neonates supports heart regeneration, while the non-regenerative adult heart displays slow and minimal collateralization. Thus, inducing robust collateral artery networks could serve as viable treatment for cardiac ischemia, but reaching this goal requires more knowledge on their developmental mechanisms and functional capabilities. Here, we use whole-organ imaging and 3D computational fluid dynamics (CFD) modeling to identify the spatial architecture of and predict blood flow through collaterals in neonate and adult hearts. We found that neonate collaterals are more numerous, larger in diameter, and, even when similar in size/number, are predicted to more effectively re-perfuse an occluded coronary network when compared to adults. CFD analysis revealed that collaterals perform better in neonates because of decreased differential pressures along their coronary artery tree. Furthermore, testing of various collateral configurations indicated that larger, more proximal collaterals are more beneficial than many smaller ones, identifying a target architecture for therapeutic interventions. Morphometric analysis revealed how the coronary artery network expands during postnatal growth. Vessel diameters do not scale with cardiac muscle growth. Instead, the coronary tree expands solely by adding additional branches of a set length, a burst of which occurs during murine puberty. Finally, we compared mouse structural and functional data to human hearts. Surprisingly, fetal human hearts possessed a very large number of small, but mature, smooth muscle cell covered collaterals while angiogram data indicated adult patients with chronic coronary occlusions contained at least two. Comparing size ratios with modeled mouse data suggested low re-perfusion capabilities of the embryonic collaterals but higher functional benefits of those in diseased adults. Our unique interdisciplinary approach allowed us to quantify the functional significance of collateral arteries during heart regeneration and repair, a critical step towards realizing their therapeutic potential.

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“…Volumetric images of sharp-filled Müller glia were traced using the Simple Neurite Tracer plugin (FIJI) 67 . We traced each glial stalk and subsequently any visible processes branching from the stalk, creating distinct paths for each process and preserving branch order relationships.…”

Section: Image Processing and Analysis: Glial Morphologymentioning

confidence: 99%

Excitatory neurotransmission activates compartmentalized calcium transients in Müller glia without affecting lateral process motility

Tworig

Coate

Feller

2021

Preprint

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Neural activity has been implicated in the motility and outgrowth of glial cell processes throughout the central nervous system. Here we explore this phenomenon in Müller glia, which are specialized radial astroglia that are the predominant glial type of the vertebrate retina. Müller glia extend fine filopodia-like processes into retinal synaptic layers, in similar fashion to brain astrocytes and radial glia which exhibit perisynaptic processes. Using two-photon volumetric imaging, we found that during the second postnatal week, Müller glial processes were highly dynamic, with rapid extensions and retractions that were mediated by cytoskeletal rearrangements. During this same stage of development, retinal waves led to increases in cytosolic calcium within Müller glial lateral processes and stalks. These comprised distinct calcium compartments, distinguished by variable participation in waves, timing, and sensitivity to an M1 muscarinic acetylcholine receptor antagonist. However, we found that motility of lateral processes was unaffected by the presence of pharmacological agents that enhanced or blocked wave-associated calcium transients. Finally, we found that mice lacking normal cholinergic waves in the first postnatal week also exhibited normal Müller glial process morphology. Hence, outgrowth of Müller glial lateral processes into synaptic layers is determined by factors that are independent of neuronal activity.

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SNT: a unifying toolbox for quantification of neuronal anatomy

Cited by 222 publications

References 62 publications

Developmental Disruption of Erbb4 in Pet1+ Neurons Impairs Serotonergic Sub-System Connectivity and Memory Formation

Developmental Disruption of Erbb4 in Pet1+ Neurons Impairs Serotonergic Sub-System Connectivity and Memory Formation

Blood flow modeling reveals improved collateral artery performance during mammalian heart regeneration

Excitatory neurotransmission activates compartmentalized calcium transients in Müller glia without affecting lateral process motility

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