We are pleased to announce the release of Neurolucida^® version 2024.1.3, which introduces key updates to offline software licensing. These updates enhance the functionality and ensure uninterrupted use of the software on systems without internet access.

Key Updates

• Offline Licensing Update:
  Reactivation is now required for systems operating without internet connectivity.

• Activation Process:
  To obtain a new offline Activation Key, please fill out this webform. Detailed instructions for completing the offline authorization process will be provided.

• Support Documentation:
  Step-by-step instructions for offline activation are available in the Neurolucida User Guide for your convenience.

For additional support or questions, please contact our customer support team at support@mbfbioscience.com.

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The file format is used in our products for neuroscience research for important applications such as digital neuron tracing, brain mapping and stereological analyses. MBF Bioscience products, including Neurolucida, Neurolucida 360, Stereo Investigator, Vesselucida 360, and NeuroInfo use this neuromorphological file format.

This file format has evolved over several decades through input and requests from many scientists who’ve been using our products. The current format is truly a collaborative effort between MBF and our users.

“We are very pleased to have received this endorsement from the INCF. It recognizes our ongoing efforts in supporting open and FAIR neuroscience, and our commitment to supporting neuroscience researchers. We’ve established rigorous standards and processes for the file format so that it can be confidently used by the entire research community”, said Jack Glaser, President of MBF Bioscience.

What does this mean for researchers who use MBF products? It expands opportunities for data sharing between individual researchers, laboratories, and within larger collaborative research initiatives. Also, it will be easier for third-party software tools to be developed and maintained that extend the usefulness of the data generated by MBF products.

The official INCF announcement stated, “The committee is pleased to see an open format from a commercial entity go through the endorsement process, and applaud MBF Bioscience for taking this very important step in support of open and FAIR neuroscience. The committee considers the governance process for MBF Bioscience’s neuromorphological file format to be well elaborated, with a sufficient mechanism for the user community to request format updates.”

MBF Bioscience and the INCF will work together to further improve the FAIRness of the standard, including implementation of the governance policy and modification of the standard’s license from the CC-BY-ND-NC to a CC-BY-ND.

The standard number is INCFSN-22-01.

Read the review report, with community feedback in comments: https://f1000research.com/documents/10-712

Read the full INCF endorsement here: https://www.incf.org/blog/incf-endorses-mbf-neuromorphological-file-format

Read a recent publication on the format:

A.E. Sullivan, S. J. Tappan, P. J. Angstman, A. Rodriguez, G. C. Thomas, D. M. Hoppes, M. A. Abdul-Karim, M. L. Heal & Jack R. Glaser. A Comprehensive, FAIR File Format for Neuroanatomical Structure Modeling. Neuroinform (2021). https://doi.org/10.1007/s12021-021-09530-x

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According to Dr. Jenny, “the 3D capabilities of Neurolucida has made it possible to better understand the distribution of small motoneurons within the motor column, and the patterns of motoneuron dendrites within the spinal cord.” The researchers are interested in comparing the patterns of motoneuron dendritic trees with the known patterns of brain-spinal cord terminal connections.

“We believe a better understanding of the motor column dendritic trees relative to descending supra-spinal inputs can be used to guide rehabilitation efforts in people recovering from stroke or spinal cord injury.”(Jenny, Cheney, 2022)

 © Elsevier B.V. All rights reserved.

Over the last four decades, advances in technology such as injections of anatomical tracers into motoneurons have provided a clearer picture of the entire dendritic tree. Dendritic trees appear to extend outward from the cell body in mostly linear and radial directions before branching. In the current research, only the proximal parts of the dendritic trees were labeled with tracer, but the patterns of the proximal dendrites were similar to the patterns seen with intracellular injections of tracer. The researchers considered the direction of dendrites seen in their material to be a reasonable estimate for the direction of the more distal unlabeled dendrites.

In the current study, the researchers used Neurolucida to digitally reconstruct the neurons from the original microscopic slides from 1983 to perform a detailed 3D analysis of dendritic tree patterns. While they observed dendrites radiating in all directions, this new analysis revealed a preference for two specific directions (either toward the gray matter at the base of the dorsal horn or to the gray matter of the medial ventral horn) suggesting the possibility that motoneuron dendritic trees extend toward functional terminal regions.

The authors plan to use Neurolucida to continue re-examining the motoneuron columns analyzed in the original 1983 study, with the ultimate goal of merging their data with data from other investigations into a 3D neuron database.

Jenny AB, Cheney PD. Monkey flexor and abductor pollicis brevis motoneuron pools: Proximal dendritic trees and small motoneurons. Neuroscience Letters. Vol. 769, 2022 Jan 19. doi: 10.1016/j.neulet.2021.136429

Jenny AB, Inukai J. Principles of Motor Organization of the Monkey Cervical Spinal Cord. Journal of Neurosci. Vol. 3, No. 3, pp. 567-575, 1983 Mar. https://www.jneurosci.org/content/jneuro/3/3/567.full.pdf

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A neurodegenerative disorder characterized by late-onset symptoms like depression, confusion, and memory loss, CTE is caused by repeated impacts to the brain. The disease is most often seen in athletes who play high impact sports and military veterans.

While CTE is known to be associated with abnormal aggregations of the tau protein, which is also observed in diseases like Alzheimer’s disease and traumatic brain injury, no research to date had explored how CTE affected neuron morphology.

In an attempt to get a glimpse into the neurodegenerative mechanisms at work in the CTE brain, researchers at Colorado College quantified the dendritic arborizations of supragranular pyramidal neurons in two regions of the human brain — the frontal and occipital lobes.

Using Neurolucida to reconstruct Golgi-stained neurons from these two regions in 16 human brains (11 cases with CTE and 5 control cases without the disease), a team of researchers led by Dr. Bob Jacobs, observed a general degeneration and greater variability between dendritic systems in CTE brains compared to controls.

Representative Neurolucida tracings of pyramidal neurons in the frontal and occipital lobes from control and chronic traumatic encephalopathy (CTE) groups. CTE tracings show greater variability in dendritic extent compared to control tracings.

According to the study, the dendritic systems of CTE brains showed reductions in seven different measures — dendritic volume, total dendritic length, mean segment length, dendritic segment count, dendritic spine number, and dendritic spine density, as well as dendritic diameter. In contrast to the occipital lobe, dendritic apathy and loss was more severe in the frontal lobe, where p-tau is known to aggregate, possibly acting as a mechanism associated with this pathology, according to the paper.

The researchers also observed a greater variability of morphological differences between dendritic systems in the CTE brains as compared to controls, which were more uniform in size and branching patterns. As outlined in the paper, this variability among neurons in CTE brains might be a result of a combination of the disease’s degenerative effects as well as reorganizational efforts to compensate for the damage.

“This study is the first to document changes in cortical dendritic systems in CTE subjects, which sheds light on an entirely different realm of CTE related neural alterations,” said Dr. Jacobs. “These dendritic changes are probably associated with at least some of the cognitive changes one sees in CTE as well.”

While the authors point out that dendritic degeneration is a normal process in the aging brain, they also explain that their observations of CTE brains in comparison to similarly aged non-CTE brains reveal a possible acceleration in dendritic loss when CTE is present.

Over the course of their study, the scientists traced 640 Golgi-stained neurons with Neurolucida.

“Neurolucida was very effective for this study. The software has come a long way in the last 30 years and has become much easier to use,” said Dr. Jacobs, who, over the course of his career, has traced over 5,000 neurons across 26 different species with the help of Neurolucida.

“I would not have had a research career without the Neurolucida system and the wonderful support of MBF over the years,” he said.

The post Researchers Observe Altered Neuropathology in CTE Brains appeared first on MBF Bioscience.

Researchers used Neurolucida to reconstruct a newly discovered type of neuron found only in the human brain, according to a study published in the journal Nature Neuroscience. Known as “rosehip” neurons because of the way they resemble a rose after its petals have fallen off, these cells feature compact, bushy axonal arborizations.

Found in the first layer of the cerebral cortex, a highly complex brain region that is thought to play an important role in consciousness, “rosehip neurons” have not been seen in mice or other laboratory animals, and scientists suggest that they may exist only in humans. Classified as inhibitory neurons, these brain cells form synapses with pyramidal neurons in layer 3 of the cerebral cortex, according to the study.

Led by Dr. Ed Lein, of the Allen Institute for Brain Science, and Dr. Gábor Tamás, a neuroscientist at the University of Szeged in Szeged, Hungary, the research team used Neurolucida to reconstruct rosehip neurons in 3D. Their reconstructions revealed that these cells display morphological characteristics that differ significantly from other types of cells found in this region of the brain.

Scientists used Neurolucida and Neurolucida Explorer to reconstruct and analyze a rosehip neuron. Image Credit: Tamas Lab, University of Szeged

Using Neurolucida Explorer to quantitatively analyze their cell reconstructions, the researchers observed similar numbers of primary dendrites in both rosehip neurons and basket cells, but fewer compared to neurogliaform cells. Meanwhile, they calculated similar total dendritic length and frequency of dendritic nodes in rosehip neurons and neurogliaform cells, but recorded differences in basket cells.

Also, their analysis revealed that the axonal branching of rosehip neurons was more robust than any other type of cell observed in this brain region, with the volume of axonal terminations, or boutons, measuring four times larger than NGFC boutons.

Furthermore, the researchers say that the rosehip neuron has a molecular marker signature of (GAD1+CCK+, CNR1–SST–CALB2–PVALB–), a signature not seen in the mouse cortex.

According to the paper, the researchers still have much to learn about the function of rosehip neurons in the human brain. Because they observed rosehip neurons connecting to their partner neurons – pyramidal neurons, in very specific places, they hypothesize that rosehip neurons might be controlling the flow of information in a distinctive way.

One next step will be to see if postmortem brains from patients with neuropsychiatric disorders display rosehip neurons with alterations, to begin investigating whether or not these newly discovered cells play a role in mental illness.

Boldog E, Bakken TE, Hodge RD, Novotny M, Aevermann BD, Baka J, Bordé S, Jennie L. Close, Diez-Fuertes F, Ding SL, Faragó N, Kocsis AK, Kovács B, Maltzer Z, McCorrison JM, Miller JA, Molnár G, Oláh G, Ozsvár A, Rózsa M, Shehata SI, Smith KA, Sunkin SM, Tran DN, Venepally P, Wall A, Puskás LG, Barzó P, Steemers FJ, Schork NJ, Scheuermann RH, Lasken RS, Lein ES, Tamás G (2018) Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type. Nature Neuroscience doi.org/10.1038/s41593-018-0205-2

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Image Courtesy: Bob Jacobs, Ph.D. , Colorado College

With the release of its new version on November 28, NeuroMorpho.org adds 9,987 new images to its archive, bringing its impressive collection of digitally reconstructed neurons to 80,012.

Scientists used MBF Bioscience’s software, Neurolucida and Neurolucida 360, to reconstruct the majority of these cells. In fact, 64 times more neurons were reconstructed with MBF Bioscience software than those imaged by our closest commercial competitor – that’s 42,121 reconstructions compared to 656. This metric demonstrates that Neurolucida and Neurolucida 360 are truly the gold standards for neuron reconstruction.

Featuring contributions from hundreds of laboratories from around the globe, NeuroMorpho.Org is the world’s leading database of publicly accessible 3D neuronal reconstructions and associated metadata. From the dragonfly to the humpback whale, researchers have access to accurate and verified data from an array of different organisms. Arranged by animal species, brain region, cell type, or contributing laboratory, each file contains specific details about the cell’s morphology such as age, developmental stage, soma volume, and number of branches – all of which are searchable.

Recently, NeuroMorpho.Org hit the 8 million download mark, with researchers in 166 different countries accessing this valuable resource, and more than one thousand published articles referencing its data

The post NeuroMorpho.Org Releases Nearly 10,000 New Neuron Reconstructions and Neurolucida leads the way appeared first on MBF Bioscience.

Analyzing cellular populations within specific anatomies in brain images requires expertise in both neuroanatomy and cellular identification. This typically involves a scientist comparing experimental images with a reference atlas and manually delineating anatomical regions and marking cell populations within. NeuroInfo^®, a revolutionary new technology from MBF Bioscience, enables researchers to automatically identify and delineate mouse brain regions based on the publicly available Allen Mouse Brain Reference Atlas.

“NeuroInfo has the potential to greatly improve our understanding of how mental disorders influence neuronal cell populations,” says Nathan O’Connor Ph.D., product manager at MBF Bioscience. “Because it makes identifying brain regions substantially faster and more accurate, researchers will be able to explore many more brain regions.”

“The Allen Mouse Brain Reference Atlas is a valuable tool to assist scientists in their research. We’re thrilled that MBF has chosen to integrate this resource into NeuroInfo,” stated Amy Bernard, Ph.D., Product Architect at the Allen Institute for Brain Science.

“Using this remarkable technology, neuroscientists will obtain more repeatable, objective analyses that have been possible to date. Thanks to the integration with the Allen Mouse Brain Reference Atlas, these analyses will be more standardized so that they can be compared across experiments and laboratories,” says Jack Glaser, President.

NeuroInfo can be used with MBF Bioscience’s slide scanning software and virtually all commercial whole slide scanners. The data from NeuroInfo seamlessly integrates with MBF Bioscience’s products including Neurolucida, Stereo Investigator, Biolucida, and BrainMaker.

The tools in NeuroInfo allow researchers to automatically delineate anatomies in the experimental specimens, and detect cells within these anatomies. NeuroInfo yields data that can be invaluable to better understand the organization and composition of the nervous system, and to further knowledge in neurogenomics, transcriptomics, proteomics, and connectomics.

The National Institute of Mental Health provides funding to support the development of NeuroInfo.

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We are happy to announce the release of Neurolucida and Stereo Investigator version 2017. This version features a completely revamped user interface that’s intuitive and easy to navigate.

“Neurolucida and Stereo Investigator version 2017 are completely redesigned to improve the user experience and increase productivity,” said Jack Glaser, President of MBF Bioscience. “The new interface makes collecting accurate data much quicker and easier.”

Version 2017 has many new performance features in addition to the new user interface. It handles large image data more efficiently, gives users the ability to dynamically edit digital reconstructions in an interactive 3D environment, and much more. Neurolucida users will also see many improvements to Neurolucida Explorer – the companion software to Neurolucida that performs all the quantitative analyses generated from neurons that are digitally reconstructed with Neurolucida.

Highlights of Stereo Investigator and Neurolucida version 2017 include:

• Easier Navigation – The ribbon bar design is task-oriented to make it easy to find what you need. A dynamic search bar and a quick access toolbar also aid productivity.

• Improved Organization – Frequently used tools are prominent and easy to access. Tools are grouped by their function, and advanced settings are easily accessible.

• Cleaner and simpler – The new user interface is modern and intuitive, making it easier to learn and to train new lab members.

• Support for the latest technological advancements in microscopic imaging devices and computer hardware.

See version 2017 in action

MBF Bioscience will exhibit and demo Neurolucida and Stereo Investigator version 2017 at the annual Experimental Biology meeting April 23 – 25 in Chicago, Illinois.

Get a quick overview of the new user interface in these 2-minute videos:

• Neurolucida version 2017
• Stereo Investigator version 2017

Register for the upcoming webinar “Using the Optical Fractionator Probe to Estimate Number of Cells”

The post MBF Bioscience Unveils Redesigned Interface for Neurolucida and Stereo Investigator version 2017 appeared first on MBF Bioscience.

Astrocytes (GFAP) in the dentate gyrus of a mouse hippocampus. Image courtesy of Dr. Ahmad Salehi, Stanford University.

It is well known that physical exercise eases the symptoms of neurodegenerative disorders like Alzheimer’s disease and helps to prevent their onset. Researchers at Stanford University are working on figuring out how it happens.

In their study, published in the journal Brain Structure and Function, scientists in Dr. Ahmad Salehi’s lab examined the effects of physical exercise on astrocytes in a region of the mouse brain that is critical for cognition – the dentate gyrus of the hippocampus. Previous studies have shown that an increase in the expression of brain-derived neurotrophic factor (Bdnf) occurs in this region after exercise (Philips, Salehi et al 2014). Bdnf is a protein that supports the survival of existing neurons and encourages new growth, playing an important role in cognitive function.

While the current study reconfirms that exercise generates increased levels of Bdnf (more than a fourfold increase in exercised mice versus non-exercised mice), it also describes several new findings including increased synaptic load in the dentate gyrus, alterations in the morphology of astrocytes, and changes in the orientation of astrocytic projections toward dentate granule cells.

The authors speculate that the changes they observed may be attributed to increased expression of a receptor called TrkB, which astrocytes express in response to increases in Bdnf levels. According to the paper, TrkB binds to Bdnf, activating the mechanisms behind neuronal development.

“Our study suggests that astrocytes actively respond and could indeed mediate the positive effects of physical exercise on the central nervous system and potentially counter degenerative processes during aging and neurodegenerative disorders,” (Fahimi, et al 2016).

The researchers used Neurolucida to determine the location, the extent, and orientation of astrocytic projections, finding a significant increase in the length of astrocytic projections in exercised mice.

“Neurolucida is one of the very few systems that combines complex morphometrical quantification with beautiful display of the results,” said Dr. Salehi, Clinical Professor, Department of Psychiatry and Behavioral Sciences at Stanford Medical School.

Since astrocytes help prevent excitotoxicity in the brain by removing excess glutamate from extracellular space, the researchers speculate that the increased length of astrocytic projections they observed in exercised mice could make this process more efficient.

Differences in the orientation of astrocytic projections were also reported, with the majority of projections of exercised mice directed toward the dentate granule cell layer – a region featuring increased levels of Bdnf release and synthesis after exercise.

The number of astrocytes in the molecular layer of the dentate gyrus in exercised and non-exercised mice was quantified with Stereo Investigator, however, there was no significant difference in astrocyte populations between the two groups.

“In summary, our study suggests that astrocytes constitute an important element in mediating the positive effects of physical exercise in the dentate gyrus of the hippocampus. Furthermore, it appears that physical exercise-induced release of Bdnf by the DG leads to a significant alteration in structure and function of astrocytes in protection against glutamate toxicity during aging and a number of neurodegenerative disorders,” (Fahimi et al 2016)

Fahimi, A., Baktir, M.A., Moghadam, S., Mojabi, F.S., Sumanth, K., McNerney, M.W., Ponnusamy, R., Salehi, A. Brain Struct Funct (2016). doi:10.1007/s00429-016-1308-8

Phillips, C., Baktir, M.A., Srivatsam, M., Salehi, A. Front. Cell. Neurosci., (2014) https://doi.org/10.3389/fncel.2014.00170

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Representative images of Iba-1+ microglia in the postnatal day 10 rat hippocampus. Image courtesy of Anna Klintsova, PhD.

Children born with fetal alcohol spectrum disorders face a range of physical and cognitive impairments including long-term deficits in learning, behavior, and immune function. In a paper published in Neuroscience, Dr. Anna Klintsova and her lab at the University of Delaware report that activation of the brain’s immune response may contribute to some of the damage caused by fetal alcohol spectrum disorders.

In their study, the researchers used Stereo Investigator and Neurolucida to examine the hypothesis that exposure to alcohol while the brain is growing rapidly is associated with abnormal microglial activation and high levels of pro-inflammatory proteins which impair learning-related plasticity; leading to neuro-developmental and psychopathological disorders.

“My lab has been using both Stereo Investigator and Neurolucida for more than a decade in all quantitative neuroanatomical studies, including the featured one,” said Dr. Anna Klintsova. “We find this software to be user-friendly, reliable and essential for obtaining unbiased results.”

They used Stereo Investigator to quantify the number of microglia in the hippocampus of neonatal rats who were exposed to alcohol during the equivalent of the third trimester of a human pregnancy. The researchers expected to see an increased number of microglia in alcohol-exposed neonatal rats, however they found a decreased number of microglia. Despite the decrease in microglia number, there was a significant increase in pro-inflammatory proteins expressed by microglia and an increase in microglial activation.

To measure microglial activation, the researchers quantified the area of cell territory using Neurolucida. Activated microglia have a smaller cell territory than resting microglia, so the smaller cell territory found in alcohol exposed rats indicates a more active state.

This research supports the hypothesis that abnormal microglia activation plays a role in fetal alcohol spectrum disorders, however more research is needed to further understand the relationship.

Boschen, K., Ruggiero, M.J., Klintsova, A.Y., (2016) Neonatal binge alcohol exposure increases microglial activation in the developing rat hippocampus. Neuroscience 324: 355–366. DOI: 10.1016/j.neuroscience.2016.03.033

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