Yearly Archives: 2017

An international research team has identified a new type of neuron which might play a vital role in humans’ ability to navigate their environments. The discovery is an important step towards understanding how the brain codes navigation behaviour at larger scales and could potentially open up new treatment strategies for people with impaired topographical orientation such as Alzheimer’s patients.

The study was published in Nature Communications.

The ability to make fine-grained assessments of location is seated in the hippocampus, located in the temporal lobe. Research shows that the precise mechanism for navigation includes hippocampal place cells, which increase or decrease in electrical activity depending on one's location.

Building on current research, the researchers investigated how large scale navigational knowledge is coded within the brain and whether this process indeed occurs in different structures within the temporal lobe.

They did this by training rats to perform a visually guided task in a figure-8 maze consisting of two loops that overlap in the middle lane. During the experiment, the researchers measured electrical activity in the brain by using a novel instrument which allowed the researchers to simultaneously record groups of neurons from four different areas. They recorded from the perirhinal cortex, hippocampus and two sensory areas. Recordings from the perirhinal cortex revealed sustained activity patterns. The level of electrical activity clearly rose and fell depending on the segment the rats were in and persisted throughout that entire segment.

The results were surprising, the researchers said, because the perirhinal cortex is currently thought to be associated with object recognition. They hypothesize that this represents a new type of neuron that helps the brain distinguish between different areas or ‘neighborhoods’ in the external environment.

The team's results offer a first glimpse into how the brain is able to code navigation behaviour at larger scales and could be especially relevant for people with an impaired capacity for topographical orientation.

In addition to offering new insights into brain mechanisms for spatial navigation at different scales, the results may guide patients with Alzheimer's or other diseases in using other spatial strategies than the ones most severely affected, the researchers say. The findings point to the perirhinal cortex as a target for treatment. Finally, research on neural replacement devices and assistive robots may benefit from this study.

Paper: “Perirhinal firing patterns are sustained across large spatial segments of the task environment”
Reprinted from materials provided by Universiteit van Amsterdam.

Although Parkinson’s disease is often associated with motor symptoms such as stiffness, poor balance and trembling, the first symptoms are often sensory and include a reduced sense of touch and smell. In a study on mice, researchers have now been able to identify neural circuits and mechanisms behind this loss of sensory perception. The study, which was published in Neuron, may open avenues to methods of earlier diagnosis.

In this study, researchers used a light puff of air to stimulate either the right or left whiskers of mice, some of which had an especially low number of dopamine cells, while using a new optogenetic tool called an optopatcher. Applying this technique, which enables the activity of neurons to be recorded during manipulation with light, they were able to see which neurons in the basal ganglia were active and when they transmitted signals.

The researchers report that the neurons in mice with very low levels of dopamine did not properly signal in response to whisker stimulation and could not accurately tell the difference between right and left. However, after being treated with a common Parkinson’s drug called L-DOPA, this ability was regained.

The researchers say they hope that the discovery will open the way for methods of earlier diagnosis.

Paper: “Dopamine Depletion Impairs Bilateral Sensory Processing in the Striatum in a Pathway-Dependent Manner”

Reprinted from materials provided by the Karolinska Institutet.

Tau proteins are involved in more than twenty neurodegenerative diseases, including various forms of dementia. These proteins clump together in patients’ brains to form neuronal tangles: protein aggregation that eventually coincides with the death of brain cells. Researchers have now discovered how tau disrupts the functioning of nerve cells, even before it starts forming tangles.

The study was published in Nature Communications.

In healthy circumstances, tau proteins are connected to the cytoskeleton of nerve cells, where they support the cells’ structural stability. In the nerve cells of patients, however, tau is dislodged from the cytoskeleton and ultimately tangles together to form protein accumulations that disrupt the nerve cell’s functioning.

But even before these protein accumulations are formed, the dislodged tau impedes the communication between nerve cells. The researchers say that they found that across fruit flies, rats, and human patients, dislodged tau ends up at nerve cell synapses, where it hooks into vesicles and inhibits communication between different nerve cells.

The next step, the researchers say, is to see if, in animal models, they can find ways to keep tau from hooking onto vesicles and, by extension, prevent nerve cell death.

Paper: "Tau association with synaptic vesicles causes presynaptic dysfunction”
Reprinted from materials provided by: VIB – Flanders Interuniversity Institute for Biotechnology

By studying cells from patients with motor neuron disease, also known as amyotrophic lateral sclerosis (ALS), researchers have revealed a detailed picture of how motor neurons — nerve cells in the brain and spinal cord that control our muscles and allow us to move, talk and breathe — decline and die.

The research, published in Cell Reports, also shows that healthy neuron-supporting cells called astrocytes may play a role in the survival of motor neurons in this type of ALS, highlighting their potential role in combating neurodegenerative diseases.

The team took skin cells from healthy volunteers and patients with a genetic mutation that causes ALS, and turned them into stem cells capable of becoming many other cell types. Using specific chemical signals, they then ‘guided’ the stem cells into becoming motor neurons and astrocytes.

Using a range of cellular and molecular techniques, the team tracked motor neurons over time to see what went wrong in the patient-derived cells compared to those from healthy people. They found that an important protein known as TDP-43 leaks out of the nucleus where it belongs, causing a chain reaction that damaged several crucial parts of the cell’s ‘machinery’. Defining the sequence of molecular events that led to motor neuron death in an experiment using human-derived cells is an important step forward.

The team suspected that astrocytes from the patients’ cells might also be affected, becoming less efficient over time and eventually dying. To test this, they mixed different combinations of healthy and ALS patient-derived motor neurons and astrocytes, and followed their fate using highly sensitive imaging approaches. They found that healthy astrocytes kept sick motor neurons alive and functioning for longer, but sick astrocytes struggled to keep even healthy motor neurons alive.

Paper: “Progressive motor neuron pathology and the role of astrocytes in a human stem cell model of VCP-related ALS”
Reprinted from materials provided by the Francis Crick Institute.

By using induced pluripotent stem cells to create endothelial cells that line blood vessels in the brain for the first time for a neurodegenerative disease, researchers have learned why Huntington’s disease patients have defects in the blood-brain barrier that contribute to the symptoms of this fatal disorder. The study, which is the first induced pluripotent stem cell-based model of the blood-brain barrier for a neurodegenerative disease, was published in Cell Reports.

The blood-brain barrier protects the brain from harmful molecules and proteins. It has been established that in Huntington's and other neurodegenerative diseases there are defects in this barrier adding to HD symptoms. What was not known was whether these defects come from the cells that constitute the barrier or are secondary effects from other brain cells.

To answer that question, researchers reprogrammed cells from HD patients into induced pluripotent stem cells, then differentiated them into brain microvascular endothelial cells — those that form the internal lining of blood vessels and prevent leakage of blood proteins and immune cells.

The researchers discovered that blood vessels in the brains of HD patients become abnormal due to the presence of the mutated Huntingtin protein, the hallmark molecule linked to the disease. As a result, these blood vessels have a diminished capacity to form new blood vessels and are leaky compared to those derived from control patients.

The chronic production of the mutant Huntingtin protein in the blood vessel cells causes other genes within the cells to be abnormally expressed, which in turn disrupts their normal functions, such as creating new vessels, maintaining an appropriate barrier to outside molecules, and eliminating harmful substances that may enter the brain.

In addition, by conducting in-depth analyses of the altered gene expression patterns in these cells, the researchers identified a key signaling pathway known as the Wnt that helps explain why these defects occur. In the healthy brain, this pathway plays an important role in forming and preserving the blood-brain barrier. The researchers showed that most of the defects in HD patients' blood vessels can be prevented when the vessels are exposed to a compound (XAV939) that inhibits the activity of the Wnt pathway.

Paper: "Huntington’s Disease iPSC-Derived Brain Microvascular Endothelial Cells Reveal WNT-Mediated Angiogenic and Blood-Brain Barrier Deficits”
Reprinted from materials provided by the University of California, Irvine.