Scientists Discover Anorexia-Driven Changes to Dendrites With Neurolucida

A digital reconstruction of a CA1 pyramidal cell from the ventral hippocampus, traced using Neurolucida with Sholl spheres at 20 micron intervals. Cells in this region featured greater dendritic length and branching versus controls.

A digital reconstruction of a CA1 pyramidal cell from the ventral hippocampus of a rat with activity-based anorexia, traced using Neurolucida with Sholl spheres at 20 micron intervals. Cells in this region featured greater dendritic length and branching versus controls.

Gaunt facial features and a frighteningly thin figure are physical hallmarks of anorexia nervosa, an eating disorder that predominantly affects adolescent girls. But in addition to extreme weight loss, changes take place that aren’t as visually apparent. For the first time, scientists in New York have found evidence of brain plasticity in the activity-based anorexia (ABA) mouse model.

Led by Dr. Chiye Aoki of New York University, the research team used Neurolucida to analyze pyramidal neurons in the rat brain. Since anorexia is linked to elevated stress hormones and anxiety, the researchers focused on the hippocampus, a region that regulates anxiety and is known to change structurally in response to hormones and stress.

“Using Neurolucida, we were able to collect, store, and analyze large amounts of data with more precision and accuracy than would have been possible without the digital interface,” said Tara Chowdhury, a graduate student working in Dr. Aoki’s lab, and first author of the paper.

“Additionally, with its very approachable interface, the software allowed us to trace dendrites, get precise thickness measurements, and categorize spine types easily during tracing. The built-in Sholl analysis and spine analysis tools resulted in quick quantification of all the measurements that would have taken hours to achieve without Neurolucida.”

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Neurolucida Helps Scientists Discover that Gorillas are Relevant in the Study of Alzheimer’s Disease

Cortical neurons containing tau termed neurofibrillary tangle seen in the human brain with Alzheimer's disease. The researchers used Neurolucida to count and chart similar neurons in the gorilla brain. 

Cortical neurons containing tau, termed neurofibrillary tangle, seen in the human brain with Alzheimer’s disease. The researchers used Neurolucida to chart similar lesions in the gorilla brain.

Humans and gorillas are approximately 98% identical on a genetic level, however there is little published research exploring Alzheimer’s disease pathology in gorillas. A new paper reports that gorillas display similarities in advanced age to humans  ̶  including the presence of Alzheimer’s disease precursors like amyloid-beta (Aβ) plaques and tau lesions.

The study, published in the Journal of Comparative Neurology, provides evidence of Alzheimer’s disease precursors in the western lowland gorilla. Their findings broaden the scientific community’s understanding of the aging brain of some our closest living relatives and offer new insights for Alzheimer’s disease research.

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Ohio State Neuroscientists Use Neurolucida to Analyze Brain Cells in Sexually Active Hamsters

A Golgi stained human neocortical pyramidal neuron. Morris et al studied cells like this to determine the affect of sexual experience on the adult brain. Using Neurolucida, they saw shorter, less extensive dendrites in hamsters which mated during adolescence versus controls.

A Golgi-stained human neocortical pyramidal neuron. Morris et al. studied cells like this to determine the effect of sexual experience on the adult brain. Using Neurolucida, they saw shorter, less extensive dendrites in hamsters which mated during adolescence versus controls.

Scientists hypothesize that during puberty, experiences influence brain development in ways that shape brain structure and even behavior in adulthood. One type of experience that often arises in the minds of pubescent teens and adolescents is sex. But a study published in the journal Hormones and Behavior suggests engaging in sexual activity too soon could be detrimental to the adult brain, and may lead to depression.

In their study of Siberian hamsters, scientists at the Wexner Medical Center at Ohio State University say adolescent sexual experiences alter brain structure.

“We used Neurolucida to reconstruct the morphology of prefrontal cortical neurons in the brains of Siberian hamsters that were exposed to sexual experience during early adolescence, later in young adulthood, or left socially isolated,” said Dr. Zachary M. Weil, an author of the study. “Interestingly, hamsters that engaged in sexual experience during early adolescence but not during other developmental periods exhibited reduced branching and dendritic length in the prefrontal cortex.”

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Japanese Researchers Develop New Optical Clearing Agent; Neurolucida Used For 3D Imaging in Study

Volume rendering of mouse cerebral cortex and hippocampus. Adult Thy1-YFP-H line mouse brain was cleared with SeeDB and imaged using two-photon microscopy. Imaging area shown is 4 x 5 mm (8 x 10 tiles), 2mm thick. We could easily make a volume rendering from a large set of 3D data (in this case, 9GB two-photon data).

Volume rendering of mouse cerebral cortex and hippocampus. Adult Thy1-YFP-H line mouse brain was cleared with SeeDB and imaged using two-photon microscopy. Imaging area shown is 4 x 5 mm (8 x 10 tiles), 2mm thick. We could easily make a volume rendering from a large set of 3D data (in this case, 9GB two-photon data).

A new optical clearing agent developed by scientists in Japan clears brain tissue samples with greater transparency and less time than other clearing agents, according to a paper published in Nature Neuroscience.

“Combined with two-photon microscopy, SeeDB allowed us to image fixed mouse brains at the millimeter-scale level,” say the authors, who after clearing the brain tissue with SeeDB, captured images with a multiphoton Olympus microscope, and visualized 3D reconstructions with Neurolucida.

A solution of fructose, water, and alpha-thioglycerol, SeeDB cleared gray and white matter brain tissue samples in three days without affecting the volume or morphology of the tissue. Dendritic spines of pyramidal neurons in the cerebral cortex was one aspect of fine morphological architecture that the authors note remained intact after SeeDB treatment.

Reconstruction of lateral dendrites of sister mitral cells. Fluorescent neuronal tracer (Alexa647 dextran amine) was electroporated into a single glomerulus to label 'sister' mitral cells associated with a common glomerulus. After optical clearing of the olfactory bulb with SeeDB, the olfactory bulb was imaged using confocal microscopy. Lateral dendrites of labeled mitral cells were reconstructed using Neurolucida. This reconstruction was used for quantitative analysis of 'sister' mitral cell distribution.

Reconstruction of lateral dendrites of sister mitral cells. Fluorescent neuronal tracer (Alexa647 dextran amine) was electroporated into a single glomerulus to label ‘sister’ mitral cells associated with a common glomerulus. After optical clearing of the olfactory bulb with SeeDB, the olfactory bulb was imaged using confocal microscopy. Lateral dendrites of labeled mitral cells were reconstructed using Neurolucida. This reconstruction was used for quantitative analysis of ‘sister’ mitral cell distribution.

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Drug for Treating Asthma Improves Cognitive Function in Down Syndrome Mouse Model

Down Syndrome Chromosome 21 image

Down syndrome is a genetic disorder caused by all or part of an extra copy of chromosome 21. Image from wikigenetics.org.

Researchers at the Stanford University School of Medicine have found that formoterol ̶  an FDA-approved drug for treating asthma and similar respiratory disorders ̶  improves cognitive function in mice genetically altered to exhibit symptoms of Down syndrome including cognitive disability.

Formoterol was chosen for the study because it activates β2 adrenergic receptors (β2ARs) on neurons, a task also carried out by norepinephrine, a neurotransmitter with a critical role in contextual learning. β2AR receptors play a key role in learning and memory, and are prevalent on dentate granule cells (DGCs) in the hippocampus. To limit the effects of the drug to the CNS, the authors used a βAR antagonist with no ability to cross the blood brain barrier.

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Neurolucida Helps Ohio State Scientists Study Melatonin’s Effects on Brain Plasticity in Mice

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An acrylic painting by Don Cooper and Leah Leverich shows the transition zone between densely packed pyramidal neurons in the CA1 region.

In spring, days grow long, and the white-footed mouse looks for a mate. For some mammals, day length prompts behaviors like breeding or camouflaging, and scientists say it’s not just the arc of the sun that kicks off these seasonal events; substances in the brain also play a part.

One important element is melatonin, a hormone that the mammalian brain secretes at night. According to a study conducted at Ohio State University, changes in the duration of melatonin secretion not only affect the behavior of white-footed mice, they also induce changes in their brains.

The group’s previous research showed that white-footed mice held in short winter-like days showed changes in the mechanism behind how memories are formed and stored in the brain, which they say is associated with impaired spatial learning and memory.

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Researchers at the University of Michigan Analyze Spine Density in Addiction-Prone Rats with Neurolucida

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Dendritic spines were quantified on terminal dendrites of medium spiny neurons (MSNs) in the nucleus accumbens core sub region of selectively-bred high- and low-responder rats following repeated cocaine treatment.

Drugs affect different people in different ways. Take cocaine for example. Not only does the drug have a stronger impact on the behavior of individuals with a particular genetic makeup, it also  initiates more profound changes in their brains.

Researchers at the University of Michigan are studying brain plasticity in cocaine-treated rats after a period of abstinence. They’re studying how abstinence from the drug affects different types of rats – those with an “addictive personality” versus their less addicted cousins.

To determine the effects of cocaine abstinence on these two groups, the researchers studied specially bred lines of rats. One group was highly sensitive to cocaine, while the other group didn’t respond as strongly to the drug. Known as “high-responder rats” (bHR) and “low-responder rats” (bLR), the two groups reacted differently to the drug treatment, with bHR rats acting more agitated during cocaine treatment, and their brains displaying more pronounced plastic changes after a period of abstinence.

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Scientists Use Neurolucida in Study of Calcium Signaling During Spontaneous Brain Activity

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A drawing of an L2 pyramidal neuron in the auditory cortex of a mouse brain rendered with Neurolucida. Biocytin-labeled neurons were visualized using the avidin:biotinylated horseradish peroxidase complex. Neurons were completely reconstructed in 3D with Neurolucida using an up-right Zeiss microscope with an oil immersion x100/1.4 numerical aperture objective.

Sensory stimuli are all around us. Street traffic zooms by. A neighbor waves “hello.” A co-worker taps away at his keyboard. Each sight, sound, and motion ignite action within our brains. But even without all these stimuli, the brain is always active.

Known as “spontaneous activity,” the activity happening inside the brain in the absence of direct stimuli follows a pattern of up and down states that scientists say is essential for processing sensory signals. Spontaneous activity may also be involved in memory.

Scientists from the Brain Research Center at the Third Military Medical University (Chongqing, China), the Center for Integrated Protein Science, SyNergy Cluster, and the Institute of Neuroscience at the Technical University of Munich (Germany) are working on figuring out how the activity occurring in the brain during “spontaneous activity” compares with what goes on during periods of sensory stimuli. Specifically, they’re looking at calcium signaling – an important element in synaptic activity during periods of both sensory stimuli and spontaneous activity, that helps neurons transmit information to other parts of the brain and body.

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Scientists in Portugal Use Neurolucida Explorer to Analyze Neuroplasticity in Depression

Nucleus Accumbens

Nucleus Accumbens

Life’s little pleasures often elude those suffering from depression, including rats, who show little interest in sugar water after experiencing stress. This behavior leads scientists to speculate that the illness might be characterized by a defect in the brain’s neural reward circuit.

Recent research focuses on a key element of this circuit – the nucleus accumbens (NAc), part of the brain region known as the ventral striatum, which is thought to regulate motivation and reward processing. In a new study of stress-induced depression in rats, researchers at the University of Minho in Braga, Portugal saw morphological changes in the dendrites of medium spiny neurons in the NAc, alongside disturbances in gene expression in this region. They also saw these changes reversed after administering antidepressants.

By using Neurolucida Explorer to analyze 3D reconstructions of medium spiny neurons generated with Neurolucida, the researchers observed longer than normal dendrites and greater spine density in the depressed rats. According to the paper, these findings contrast with studies of the hippocampus and prefrontal cortex, where chronic stress leads to shorter dendrites.

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Cincinnati Scientists Use Neurolucida in Epilepsy Study

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Scientists hypothesize that seizures occur because brain cells fire in places they’re not supposed to. Dentate granule cells (DGCs), a type of neuron born throughout adulthood, sometimes migrate into a different region of the dentate gyrus, a part of the hippocampus. These abnormal newborn cells sprout axons called “mossy fibers” that form connections with neighboring DGCs in the inner molecular layer, causing synaptic changes that wouldn’t normally occur in healthy brains.

Much research has been done on this phenomenon, but neuroscientists still struggle to understand what exactly its relationship is with epilepsy.

A new study by researchers at the Cincinnati Children’s Hospital Medical Center validates hypotheses about the role of abnormal DGCs in epilepsy. In their study of a transgenic mouse model of temporal lobe epilepsy (TLE), the scientists observed a relationship between the presence of deviant DGCs and seizure frequency.

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