3D Reconstructions of Neurons Reveal More Branching in Sedentary Rats

Left: A neuron from the brain of a rat that exercised for two hours each day. Right: A neuron from the brain of a sedentary rat.

Left: A neuron from the brain of a rat that exercised for two hours each day.
Right: A neuron from the brain of a sedentary rat. Scientists saw greater branching in inactive versus active rats. (Image courtesy of Dr. Patrick Mueller)

Scientists discovered that inactivity makes brain cells grow, but not in a good way. In a study published in the Journal of Comparative Neurology, researchers found more neuronal branching in sedentary rats compared to active rats. The growth occurred in a region of the brain that controls blood pressure, leading the scientists to hypothesize that these changes may be part of the reason inactivity is linked to an increased risk of heart disease.

Using Neurolucida to reconstruct neurons in 3D, the scientists at Dr. Patrick Mueller’s lab at Wayne State University School of Medicine, in Detroit, saw structural differences between the brains of active and inactive rats.

Focusing on the rostral ventrolateral medulla (RVLM) – an area that controls several critical biological processes that rats as well as humans do unconsciously, like swallowing, breathing, and regulating blood pressure, the scientists saw longer dendrites, more dendritic branching, and more intersections with other neurons in sedentary rats.

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Researchers Restore Neuron Branching in Model of Mutant NHE6 Gene

Mice with the  NHE6 gene mutation show less dendritic branching. Using Neurolucida, researchers traced a GFP-labeled neuron reconstructed with confocal z stacks in a wild type mouse (left) and a mouse with a mutant NHE6 gene (right).

Mice with the NHE6 gene mutation show less dendritic branching. Using Neurolucida, researchers traced a GFP-labeled neuron reconstructed with confocal z stacks in a wild type mouse (left) and a mouse with a mutant NHE6 gene (right). Image courtesy of first author Qing Ouyang, PhD, Alpert Medical School, Brown University.

Children with the neurogenetic disorder Christianson Syndrome experience delays in language and learning; they may also have seizures, and display symptoms of autism. Scientists say these disorders are a result of stunted brain cell growth, which occurs because of a mutation in the gene that produces the protein NHE6—a protein also mutant in several forms of autism.

Neurons in human brains with the mutant gene don’t branch as robustly or form connections as well as neurons in normal brains. But researchers at Brown University may have found a way to restore the ability of these cells to grow properly.

In their study, published in the journal Neuron, senior author Dr. Eric Morrow and his team describe a signaling pathway for neuronal growth involving NHE6. Using a mouse model with an NHE6 gene mutation, they found that reduced levels of NHE6 combined with increased acidity in a cell’s endosome, results in a depletion of the receptor protein TrkB, a key player in the growth and branching of axons and dendrites.

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Neurons in the Basal Forebrain are Exquisitely Organized

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A micrograph of the nucleus basalis of Meynert, a group of neurons in the basal forebrain that produces most of the acetylcholine supplied to the cerebral cortex.
Image from Wikimedia Commons

The loss of cholinergic neurons is one of the earliest pathological events of Alzheimer’s disease. Cholinergic neurons in the basal forebrain supply the cerebral cortex with acetylcholine, an important neurotransmitter that plays a role in learning, memory, and attention. Details about the function and organization of basal forebrain (BF) neurons are not well understood, but Dr. Laszlo Zaborszky has recently uncovered new information about the structure of this complex area of the brain.

In a paper published in Cerebral Cortex, Dr. Zaborszky and his team report that they discovered exquisite organization in the basal forebrain of rats; the extent of overlap between basal forebrain neuronal populations correlates with the connectivity strength between their cortical targets. This means that basal forebrain neurons that overlap extensively project to frontal and posterior cortical areas that are strongly connected. Connectivity strength between cortical areas is defined by the number of neurons in a defined posterior cortical area that project to a defined area in the frontal cortex. Continue reading “Neurons in the Basal Forebrain are Exquisitely Organized” »

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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MBF customer Dr. Thomas Südhof wins Nobel Prize

The Nobel Prize in Physiology or Medicine was awarded to Drs. Thomas Südhof, James Rothman, and Randy Schekman for discovering the principles of how molecules are transported within cells and in between cells and how they are delivered to the right place at the right time. Disruptions in this precise system are implicated in numerous neurological and immunological disorders.sudoflab

Dr. Sudhof uncovered how neurotransmitters are released into a synaptic cleft precisely when they need to be. His research explained the molecular machinery that responds to an influx of calcium and signals the release of neurotransmitters.

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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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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

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

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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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