Hippocampal Neurons Change After Melatonin Injection

Representative dendrites of dentate gyrus neurons of Siberian hamsters injected with melatonin (stained with Cresyl violet). Ikeno et al found hamsters injected with melatonin displayed decreased spine density on neurons in the dentate gyrus.

Representative dendrites of dentate gyrus neurons of Siberian hamsters injected with melatonin (stained with Cresyl violet). Ikeno et al found hamsters injected with melatonin displayed decreased spine density on neurons in the dentate gyrus. Image courtesy of Tomoko Ikeno, Ph.D.

Night falls and a powerful hormone called melatonin kicks in. The gears of the circadian clock are turning as you get ready for bed and soon drift off to dreamland. But all is not quiet in the brain. In response to the circadian rhythm, neurons are transforming.

A new study published in the journal Hippocampus found that melatonin prompts dendrites to grow longer in one part of the brain, while in another part the hormone causes dendritic spine loss.

In their study, scientists at Ohio State University injected Siberian hamsters with a dose of melatonin in the afternoon, several hours before a natural increase in the hormone would normally occur. Four hours after the injection, they used Neurolucida to examine sections of their brains, reconstructing neurons in two areas of the hippocampus – the CA1 and dentate gyrus. They then used the software to calculate the number of branch points and length of dendrites in their reconstructions. What they saw was longer, more complex dendrites in the CA1 region of the hippocampus of hamsters that received melatonin versus those that received a placebo. Then they analyzed spine density, finding that hamsters that received melatonin had decreased spine density in the dentate gyrus than the control group.

“By using Neurolucida, we found that melatonin treatment induced rapid remodeling of hippocampal neurons and induced a nighttime state of the hippocampal neuronal morphology,” said Dr. Tomoko Ikeno, who worked with Dr. Randy Nelson on the study.

The “nighttime state” she refers to is characterized by the presence of certain hormones produced during the dark hours of night. In their analysis, the researchers saw elevated levels of Period1 and Bmal1 after melatonin injection. These hormones are expressed by genes associated with the circadian clock, and their presence offers evidence that “melatonin functions as a nighttime signal to coordinate the diurnal rhythm” and that this rhythm compels hippocampal neurons to change structurally, according to the paper.

Ikeno, T. and Nelson, R. J. (2014), Acute melatonin treatment alters dendritic morphology and circadian clock gene expression in the hippocampus of Siberian Hamsters. Hippocampus. doi: 10.1002/hipo.22358

 

Dendritic Spine Loss Reported in Schizophrenia and Bipolar Disorder

Golgi-stained human brain tissue from the dorsolateral prefrontal cortex.

Golgi-stained human brain tissue from the dorsolateral prefrontal cortex.

Schizophrenia and bipolar disorder are very different mental illnesses, but researchers are discovering evidence that the two disorders have some common pathologies. According to a recent study, a shared characteristic appears to be dendritic spine loss.

The researchers used Neurolucida to study pyramidal cells in human brain tissue from individuals with schizophrenia (n=14), individuals with bipolar disorder (n=9) and unaffected control participants (n=19). The pyramidal cells were located in the dorsolateral prefrontal cortex – a region that plays a key role in working memory. Bipolar patients showed significantly reduced spine density (10.5 percent) compared to control. Schizophrenic patients also showed lower spine density (6.5 percent), but this number just missed significance when compared to control patients. Individuals with both illnesses showed a lower number of spines per dendrite, as well as reduced dendritic length compared to controls.

To obtain these results, researchers analyzed 15 Golgi-stained pyramidal cells in each tissue sample. They used Neurolucida to reconstruct the longest dendrite on the pyramidal cells and to mark spines. After the researchers finished reconstructing the cells, Neurolucida provided them with important data about the dendrites and spines.

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Two 2014 Nobel Prize Laureates Used Neurolucida in their Groundbreaking Research

May-Britt and Edvard Moser

Drs. May-Britt and Edvard Moser Image from GEIR MOGEN / NTNU

Drs. May-Britt and Edvard Moser were awarded the 2014 Nobel Prize in Physiology or Medicine for discovering the cells that form a network for spatial navigation in the brain, and we’re proud to say they are MBF Bioscience customers and used Neurolucida in their research.

In 2006, the Norwegian husband and wife team published a paper in the journal Science entitled “Conjunctive Representation of Position, Direction, and Velocity in Entorhinal Cortex” – a pivotal step in a line of research initiated in 1971 by co-laureate Dr. John O’Keefe (The Hippocampus as a Spatial Map). In their study, the scientists used Neurolucida to create 3D reconstructions of a complex network of neurons that make it possible for rats, and other animals, including humans, to navigate the world around them.

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Anorexia Accelerates the Development of the Rat Hippocampus

spine_edited

This image stack was used in the study to analyze spine density. Image courtesy of Tara Chowdhury, Ph.D. first author of the study.

To find out how anorexia nervosa changes the brain, scientists at New York University are studying a rat model of the disease called activity-based anorexia (ABA). Previously, they discovered that ABA rats develop unusually robust dendritic branching of neurons in part of the hippocampus. Their new study takes those findings a step further, illuminating more differences between the brains of healthy versus ABA rats, and offering evidence that ABA rats may be developing too early, closing a critical period of development too soon.

But before making any conclusions about ABA brains, the researchers made some interesting discoveries about normal brain development. Using Neurolucida to analyze CA1 pyramidal cells in the stratum radiatum layer of the ventral hippocampus, they found that after puberty, around postnatal day 51, dendrites go through a growth spurt, more than doubling the number of branches seen seven days earlier. This growth spurt is followed by a decrease, or a pruning, which the researchers say is part of the normal maturation process.

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Scientists Use Neurolucida to Create 3D Reconstructions of Placental Villous Trees

(a,b) Comparison of the microscopic aspects of a thin (4–6 μm) histological section of a human placenta after staining with hematoxylin/eosin (a) with the microscopic aspects of a whole-mount isolated villous tree after staining with hematoxylin (b). The scale bars in a and b are 250 μm. (a) Various cross- and longitudinal sections of villi can be recognized. The stromal architecture inside the sectioned villi is visible. The cross-sections of branches belong to an unknown number of villous trees. (b) A single villous tree is visible, and branches are not sectioned. The hierarchical positions of nodes (branching points) and the branching topology can be recognized.

(a,b) Comparison of the microscopic aspects of a thin (4–6 μm) histological section of a human placenta after staining with hematoxylin/eosin.

When neuroscientists started studying neurons in 3D, it revolutionized brain science. Now, for the first time, scientists are using this same technology to study the human placenta, and they’ve made some fascinating new discoveries about its structure.

Using Neurolucida to create 3D reconstructions of villous trees – three-dimensional structures in the placenta that facilitate gas and nutrient exchange between the fetus and mother – researchers in Munich, Germany uncovered a wealth of information about their architecture.

For the first time, they analyzed the complexity of villous tree branches and branching, determined the number and location of nodes (branching points), and measured branch angles, discovering a surprising correlation between the branching angle of terminal branchesand the fetoplacental weight ratio (BW/PW) – a calculation commonly used to measure fetal health in prenatal medicine.

“The results show that 3D analysis with Neurolucida reaches beyond the horizons of 2D histology, the current gold standard in placenta morphology/pathology,” said Dr. Hans-Georg Frank, an author of the study. Continue reading “Scientists Use Neurolucida to Create 3D Reconstructions of Placental Villous Trees” »

New Neurons Erase Memories

Dentate gyrus

Neurogenesis occurs in the dentate gyrus, pictured here, from birth through adulthood.

A baby laughs at an elephant at the zoo. A toddler runs across a beach. Small children make memories all the time, but how many will they recall as the years pass? Maybe none at all. The phenomenon is called “infantile amnesia,” and scientists may have pinpointed a reason for why it occurs – neurogenesis.

Researchers at the Hospital for Sick Children in Toronto say that when new brain cells integrate into existing circuitry, they remodel the structure of networks already in place, wiping out the information previously stored there. This process is prevalent in infancy and early childhood because this is the time when new brain cells are being generated faster and more frequently than at any other time in a human being’s life. Humans and other mammals spawn new neurons throughout their lifespans, although the rate of neurogenesis decreases significantly with age.

In their paper, published in Science, the researchers explain how recent studies have focused on how new brain cells can lead to new memories, but the Toronto team speculated that neurogenesis could also wipe away memories. To test their hypothesis, they conducted a series of studies on populations of newborn and adult mice. Neuron development in mice occurs in much the same way as in humans, with rapid cell genesis in infancy that tapers off with age.

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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

File:Nucleus basalis of Meynert - intermed mag.jpg

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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