(Image caption: In this artist’s representation of the adult subependymal neurogenic niche (viewed from underneath the ependyma), electrical signals generated by the ChAT+ neuron give rise to newborn migrating neuroblasts, seen moving over the underside of ependymal cells. Credit: Illustration by O’Reilly Science Art.)

Neuron Tells Stem Cells to Grow New Neurons

Duke researchers have found a new type of neuron in the adult brain that is capable of telling stem cells to make more new neurons. Though the experiments are in their early stages, the finding opens the tantalizing possibility that the brain may be able to repair itself from within.

Neuroscientists have suspected for some time that the brain has some capacity to direct the manufacturing of new neurons, but it was difficult to determine where these instructions are coming from, explains Chay Kuo, M.D. Ph.D., an assistant professor of cell biology, neurobiology and pediatrics.

In a study with mice, his team found a previously unknown population of neurons within the subventricular zone (SVZ) neurogenic niche of the adult brain, adjacent to the striatum. These neurons expressed the choline acetyltransferase (ChAT) enzyme, which is required to make the neurotransmitter acetylcholine. With optogenetic tools that allowed the team to tune the firing frequency of these ChAT+ neurons up and down with laser light, they were able to see clear changes in neural stem cell proliferation in the brain.

The findings appeared as an advance online publication June 1 in the journal Nature Neuroscience.

The mature ChAT+ neuron population is just one part of an undescribed neural circuit that apparently talks to stem cells and tells them to increase new neuron production, Kuo said. Researchers don’t know all the parts of the circuit yet, nor the code it’s using, but by controlling ChAT+ neurons’ signals Kuo and his Duke colleagues have established that these neurons are necessary and sufficient to control the production of new neurons from the SVZ niche.

"We have been working to determine how neurogenesis is sustained in the adult brain. It is very unexpected and exciting to uncover this hidden gateway, a neural circuit that can directly instruct the stem cells to make more immature neurons," said Kuo, who is also the George W. Brumley, Jr. M.D. assistant professor of developmental biology and a member of the Duke Institute for Brain Sciences. "It has been this fascinating treasure hunt that appeared to dead-end on multiple occasions!"

Kuo said this project was initiated more than five years ago when lead author Patricia Paez-Gonzalez, a postdoctoral fellow, came across neuronal processes contacting neural stem cells while studying how the SVZ niche was assembled.

The young neurons produced by these signals were destined for the olfactory bulb in rodents, as the mouse has a large amount of its brain devoted to process the sense of smell and needs these new neurons to support learning. But in humans, with a much less impressive olfactory bulb, Kuo said it’s possible new neurons are produced for other brain regions. One such region may be the striatum, which mediates motor and cognitive controls between the cortex and the complex basal ganglia.

"The brain gives up prime real estate around the lateral ventricles for the SVZ niche housing these stem cells," Kuo said. "Is it some kind of factory taking orders?" Postdoctoral fellow Brent Asrican made a key observation that orders from the novel ChAT+ neurons were heard clearly by SVZ stem cells.

Studies of stroke injury in rodents have noted SVZ cells apparently migrating into the neighboring striatum. And just last month in the journal Cell, a Swedish team observed newly made control neurons called interneurons in the human striatum for the first time. They reported that interestingly in Huntington’s disease patients, this area seems to lack the newborn interneurons.

"This is a very important and relevant cell population that is controlling those stem cells," said Sally Temple, director of the Neural Stem Cell Institute of Rensselaer, NY, who was not involved in this research. "It’s really interesting to see how innervations are coming into play now in the subventricular zone."

Kuo’s team found this system by following cholinergic signaling, but other groups are arriving in the same niche by following dopaminergic and serotonergic signals, Temple said. “It’s a really hot area because it’s a beautiful stem cell niche to study. It’s this gorgeous niche where you can observe cell-to-cell interactions.”

These emerging threads have Kuo hopeful researchers will eventually be able to find the way to “engage certain circuits of the brain to lead to a hardware upgrade. Wouldn’t it be nice if you could upgrade the brain hardware to keep up with the new software?” He said perhaps there will be a way to combine behavioral therapy and stem cell treatments after a brain injury to rebuild some of the damage.

The questions ahead are both upstream from the new ChAT+ neurons and downstream, Kuo says. Upstream, what brain signals tell ChAT+ neurons to start asking the stem cells for more young neurons? Downstream, what’s the logic governing the response of the stem cells to different frequencies of ChAT+ electrical activity?

There’s also the big issue of somehow being able to introduce new components into an existing neuronal circuit, a practice that parts of the brain might normally resist. “I think that some neural circuits welcome new members, and some don’t,” Kuo said.

How to Erase a Memory – And Restore It

Researchers at the University of California, San Diego School of Medicine have erased and reactivated memories in rats, profoundly altering the animals’ reaction to past events.

The study, published in the June 1 advanced online issue of the journal Nature, is the first to show the ability to selectively remove a memory and predictably reactivate it by stimulating nerves in the brain at frequencies that are known to weaken and strengthen the connections between nerve cells, called synapses.

“We can form a memory, erase that memory and we can reactivate it, at will, by applying a stimulus that selectively strengthens or weakens synaptic connections,” said Roberto Malinow, MD, PhD, professor of neurosciences and senior author of the study.

Scientists optically stimulated a group of nerves in a rat’s brain that had been genetically modified to make them sensitive to light, and simultaneously delivered an electrical shock to the animal’s foot. The rats soon learned to associate the optical nerve stimulation with pain and displayed fear behaviors when these nerves were stimulated.

Analyses showed chemical changes within the optically stimulated nerve synapses, indicative of synaptic strengthening.

In the next stage of the experiment, the research team demonstrated the ability to weaken this circuitry by stimulating the same nerves with a memory-erasing, low-frequency train of optical pulses. These rats subsequently no longer responded to the original nerve stimulation with fear, suggesting the pain-association memory had been erased.

In what may be the study’s most startlingly discovery, scientists found they could re-activate the lost memory by re-stimulating the same nerves with a memory-forming, high-frequency train of optical pulses. These re-conditioned rats once again responded to the original stimulation with fear, even though they had not had their feet re-shocked.

“We can cause an animal to have fear and then not have fear and then to have fear again by stimulating the nerves at frequencies that strengthen or weaken the synapses,” said Sadegh Nabavi, a postdoctoral researcher in the Malinow lab and the study’s lead author.

In terms of potential clinical applications, Malinow, who holds the Shiley Endowed Chair in Alzheimer’s Disease Research in Honor of Dr. Leon Thal, noted that the beta amyloid peptide that accumulates in the brains of people with Alzheimer’s disease weakens synaptic connections in much the same way that low-frequency stimulation erased memories in the rats. “Since our work shows we can reverse the processes that weaken synapses, we could potentially counteract some of the beta amyloid’s effects in Alzheimer’s patients,” he said.

Εngineer invents safe way to transfer energy to medical chips in the body

A Stanford electrical engineer has invented a way to wirelessly transfer power deep inside the body, and then use this power to run tiny electronic medical gadgets such as pacemakers, nerve stimulators or new sensors and devices yet to be developed.

The discoveries reported May 19 in the Proceedings of the National Academy of Sciences culminate years of efforts by Ada Poon, assistant professor of electrical engineering, to eliminate the bulky batteries and clumsy recharging systems that prevent medical devices from being more widely used.

The technology could provide a path toward a new type of medicine that allows physicians to treat diseases with electronics rather than drugs.

"We need to make these devices as small as possible to more easily implant them deep in the body and create new ways to treat illness and alleviate pain," said Poon.

Poon’s team built an electronic device smaller than a grain of rice that acts as a pacemaker. It can be powered or recharged wirelessly by holding a power source about the size of a credit card above the device, outside the body.

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Using thoughts to control airplanes

Pilots of the future could be able to control their aircraft by merely thinking commands. Scientists of the Technische Universität München and the TU Berlin have now demonstrated the feasibility of flying via brain control – with astonishing accuracy.

The pilot is wearing a white cap with myriad attached cables. His gaze is concentrated on the runway ahead of him. All of a sudden the control stick starts to move, as if by magic. The airplane banks and then approaches straight on towards the runway. The position of the plane is corrected time and again until the landing gear gently touches down. During the entire maneuver the pilot touches neither pedals nor controls.

This is not a scene from a science fiction movie, but rather the rendition of a test at the Institute for Flight System Dynamics of the Technische Universität München (TUM). Scientists working for Professor Florian Holzapfel are researching ways in which brain controlled flight might work in the EU-funded project “Brainflight”.

"A long-term vision of the project is to make flying accessible to more people," explains aerospace engineer Tim Fricke, who heads the project at TUM. "With brain control, flying, in itself, could become easier. This would reduce the work load of pilots and thereby increase safety. In addition, pilots would have more freedom of movement to manage other manual tasks in the cockpit." 

Surprising accuracy

The scientists have logged their first breakthrough: They succeeded in demonstrating that brain-controlled flight is indeed possible – with amazing precision. Seven subjects took part in the flight simulator tests. They had varying levels of flight experience, including one person without any practical cockpit experience whatsoever. The accuracy with which the test subjects stayed on course by merely thinking commands would have sufficed, in part, to fulfill the requirements of a flying license test. “One of the subjects was able to follow eight out of ten target headings with a deviation of only 10 degrees,” reports Fricke. Several of the subjects also managed the landing approach under poor visibility. One test pilot even landed within only few meters of the centerline.

The TU München scientists are now focusing in particular on the question of how the requirements for the control system and flight dynamics need to be altered to accommodate the new control method. Normally, pilots feel resistance in steering and must exert significant force when the loads induced on the aircraft become too large. This feedback is missing when using brain control. The researchers are thus looking for alternative methods of feedback to signal when the envelope is pushed too hard, for example.

Electrical potentials are converted into control commands

In order for humans and machines to communicate, brain waves of the pilots are measured using electroencephalography (EEG) electrodes connected to a cap. An algorithm developed by scientists from Team PhyPA (Physiological Parameters for Adaptation) of the Technische Universität Berlin allows the program to decipher electrical potentials and convert them into useful control commands.

Only the very clearly defined electrical brain impulses required for control are recognized by the brain-computer interface. “This is pure signal processing,” emphasizes Fricke. Mind reading is not possible.

A Mexican Scientist Just Invented a ‘Telekinesis’ Helmet

A researcher just made a remarkable breakthrough in the area of brain-computer interfaces—creating a rig that allows a user to operate machines with thought alone, almost literally granting a form of ‘telekinesis’ over attached devices.

Brain-computer interfaces are a rapidly expanding area of research and industry. Though the technology to read brainwaves from the head’s surface has been around for decades, scientists and engineers have only recently created numerous systems to read signals directly from the brain and translate them into commands that control computers.

In the future, these technologies could allow people with physical disabilities to control their environment through thought alone—the brain-computer interface effectively grants users a form of telekinesis. With an increasingly digital world, brain-computer interfaces (BCIs) could allow future generations to interact with technology telepathically. Many of the early BCI studies were promising, but the technology was difficult to use and mentally exhausting.

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Exceptional Evolutionary Divergence of Human Muscle and Brain Metabolomes Parallels Human Cognitive and Physical Uniqueness

Metabolite concentrations reflect the physiological states of tissues and cells. However, the role of metabolic changes in species evolution is currently unknown. Here, we present a study of metabolome evolution conducted in three brain regions and two non-neural tissues from humans, chimpanzees, macaque monkeys, and mice based on over 10,000 hydrophilic compounds. While chimpanzee, macaque, and mouse metabolomes diverge following the genetic distances among species, we detect remarkable acceleration of metabolome evolution in human prefrontal cortex and skeletal muscle affecting neural and energy metabolism pathways. These metabolic changes could not be attributed to environmental conditions and were confirmed against the expression of their corresponding enzymes. We further conducted muscle strength tests in humans, chimpanzees, and macaques. The results suggest that, while humans are characterized by superior cognition, their muscular performance might be markedly inferior to that of chimpanzees and macaque monkeys.

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