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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Hawaii Scientists Measure Density of Parvalbumin-Interneurons With Stereo Investigator

Reduced density of PV-interneurons in Sepp1-/- mice. (A) Representative images showing PV expression in the hippocampus (left column) and inferior colliculus (middle and right columns) of WT Sepp1+/+ (top row) and Sepp1-/- (bottom row) mice. Higher magnification images of the inferior colliculus (far right) (B), Mean density of PV-interneurons per mm3 (+-SEM, n=6 per genotype) in brain regions investigated: SC; MS; DG, CA1, and CA2/3 of the hippocampus; IC. * P<0.01. Figure courtesy of Matthew W. Pitts, Ph.D.

Reduced density of PV-interneurons in Sepp1-/- mice. (A) Representative images showing PV expression in the hippocampus (left column) and inferior colliculus (middle and right columns) of WT Sepp1+/+ (top row) and Sepp1-/- (bottom row) mice. Higher magnification images of the inferior colliculus (far right) (B), Mean density of PV-interneurons per mm3 (+-SEM, n=6 per genotype) in brain regions investigated: SC; MS; DG, CA1, and CA2/3 of the hippocampus; IC. * P<0.01. Figure courtesy of Matthew W. Pitts, Ph.D.

Foods like tuna fish and Brazil nuts are rich in selenium, a mineral that scientists say has antioxidant effects, keeping the brain healthy and free of clutter so cells can work smoothly together. A key element of this process is Selenoprotein P (Sepp1) – a protein that delivers selenium to neurons by binding with another protein – ApoER2. Neuroscientists at the University of Hawaii say Sepp1 plays a critical role in brain function, and deficits may play a part in mental illnesses like schizophrenia.

In their study published in Neuroscience, the researchers investigate the relationship between Sepp1 and parvalbumin (PV)-interneurons – a class of brain cell that controls firing rates and synchronizes spiking activity among other groups of neurons. Previous research shows that these cells need selenium to develop properly, so the scientists set out to find out what affect a Sepp1 deficit would have on the mouse brain.

Led by Dr. Matthew W. Pitts, the research team compared the brains of wild type mice with Sepp1 deficient mice. They used a Zeiss Axioskop microscope equipped with Stereo Investigator to conduct a stereological analysis of PV-interneurons in several different regions of the mouse brain. Using Stereo Investigator’s optical fractionator probe, they observed reduced numbers of PV-interneurons along with elevated oxidative stress in the inferior colliculus of Sepp1 deficient mice, a region involved in processing auditory information.

“Stereo Investigator was particularly useful for estimating cell density in larger brain structures, such as the inferior colliculus,” said Dr. Pitts.

Since scientists speculate that dysfunctional PV-interneuron networks may be involved in neuropsychiatric conditions, the researchers conducted behavioral tests that showed impairments in contextual fear extinction, latent inhibition, and sensorimotor gating in the Sepp1 deficient mice – behaviors observed in some mental illnesses.

“Previous studies (Valentine et al., 2008) and our findings together indicate that ApoER2- mediated uptake of Sepp1 serves an important neuroprotective role in the inferior colliculus,” the authors say in their paper. “These findings may have relevance to neuropsychiatric conditions in which dysfunc- tional PV-interneuron networks have been implicated, such as epilepsy and schizophrenia.”

Pitts M.W., Raman A.V., Hashimoto A.C., Todorovic C., Nichols R.A., Berry M.J. Deletion of selenoprotein P results in impaired function of parvalbumin interneurons and alterations in fear learning and sensorimotor gating. Neuroscience. 2012 Apr 19;208:58-68. doi: 10.1016/j.neuroscience.2012.02.017.

 

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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New Zealand Scientists Use Stereo Investigator to Develop a New Model for Human Extreme Prematurity

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Oligodendrocytes, pictured here with a green fluorescent protein, form a myelin sheath – the insulation around axons. The extremely premature brain features a lower number of pre-oligodendrocytes, thereby decreasing myelination, a characteristic which has been associated with ADHD. Image courtesy of Wikimedia Commons.

Each year, nearly ninety thousand children are born extremely premature in the United States – that is, before 28 weeks gestation. Most of them survive, but about half the survivors suffer from severe health problems throughout their childhood and into adulthood, including learning and behavioral disorders such as ADHD.

“Treatment options are clearly urgently required to prevent the brain damage and associated memory deficits that follow extremely premature birth,” say the authors of a study published last month in the Journal of Neuroscience.

Treatment options are limited, the authors say, because current small animal models fall short in their mimicry of the extremely premature human brain. However, the researchers from the University of Otago in New Zealand have come up with a new animal model for human extreme prematurity, which they say more closely resembles the pathological and behavioral deficits seen among this population.

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Scientists Assess Kidney Damage with Stereo Investigator, Determine Ultrasound Prevents Organ Injury

Using the virtual tissue function of Stereo Investigator a series of photos of each section was captured using the 5X objective and automatically stitched together to form a montage of the entire section of kidney that clearly represents the degree of injury.  Kidneys are from mice treated either with vehicle (0.3 M sodium bicarbonate) or a single injection of folic acid (250 mg/kg, ip) in sodium bicarbonate, and mice were euthanized after 14 days. Injection of folic acid has been used as one model of chronic kidney disease. The degree of fibrosis in the kidney, revealed here by Masson’s trichrome stain (blue: collagen deposition), was determined using the area fraction fractionator probe in Stereo Investigator.

Using the Virtual Tissue module with Stereo Investigator, a series of photos of each kidney section was captured using the 5X objective and then automatically stitched together to form a montage of the entire section of kidney that clearly represents the degree of injury.  Kidneys are from mice treated either with vehicle (0.3 M sodium bicarbonate) or a single injection of folic acid (250 mg/kg, ip) in sodium bicarbonate. The mice were euthanized after 14 days. Injection of folic acid has been used as one model of chronic kidney disease. The degree of fibrosis in the kidney, revealed here by Masson’s trichrome stain (blue: collagen deposition), was determined using the area fraction fractionator probe in Stereo Investigator.

When it comes to health, kidneys are critical. From regulating blood composition to maintaining calcium levels, the pair of bean-shaped organs perform several essential tasks. Needless to say, interruption to kidney function can be disastrous.

Working with scientists in South Korea, researchers at the University of Virginia found a surprisingly simple treatment for renal ischemia-reperfusion injury (IRI) in mice, which is a model of acute kidney injury (AKI) in humans.

The researchers found that mice exposed to ultrasound prior to IRI “had preserved kidney structure and function accompanied by a reduction in tissue inflammation,” they report in their paper published this month in the Journal of the American Society of Nephrology.

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Boston University Scientists Use AutoNeuron and AutoSynapse to Compare Neurons in the Visual and Prefrontal Cortices

MBF_Figure

Use of Neurolucida to assess the detailed morphology – including spines and synapses – of a layer 3 pyramidal neuron from the anterior cingulate cortex of a rhesus monkey. A) 40x confocal image of a layer 3 pyramidal neuron that was filled with biocytin during whole-cell patch-clamp recordings and subsequently processed with Alexa-Streptavidin-488. B) Basilar dendritic segment (indicated by the box in A), scanned in 2 channels: green= the neuron; red= VGat. C) Dendritic reconstruction indicated in light blue. Spine subtypes identified by the AutoSpine module (magenta= mushroom; yellow= thin; red= stubby). D) VGat-positive appositions (indicated by white dots) against the dendritic shaft and spines identified with AutoSynapse. Scale bars: A= 20 µm; B= 2 µm

The ball comes flying and you swing the bat. A car pulls out and you hit the brakes. As we go about our daily routines, we process everything we see in a region in the back of our brains known as the visual cortex. But when we sit down to plan a kitchen remodel, or next summer’s vacation, an area in the front of the brain gets activated, the prefrontal cortex, a region involved in higher level thinking.

Recent research has offered insight into the structure and function of neurons in these two distinct brain regions. Scientists at the Luebke Lab at Boston University set out to find out more about their morphology, and if their structural differences affect their behavior. Their study, published in the Journal of Neuroscience offers evidence that pyramidal neurons in the primary visual cortex (V1) and dorsolateral granular prefrontal cortex (dlPFC) of the rhesus monkey display “marked electrophysiological and structural differences.”

“We chose to examine these two areas because they represent distinct ends of the spectrum of neocortical complexity and specialization, from primary sensory processing by V1 to mediation of high-order cognitive processes by dlPFC,” the authors say in their paper.

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

CA1_to_subiculum4

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

Waselus_SpineImage_Pseudocolor

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

calcium_signaling_neurlucida_neuron

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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