Posts Tagged ‘Ruth Williams’

by Ruth Williams

By activating a particular pattern of nerve endings in the brain’s olfactory bulb, researchers can make mice smell a non-existent odor, according to a paper published June 18 in Science. Manipulating these activity patterns reveals which aspects are important for odor recognition.

“This study is a beautiful example of the use of synthetic stimuli . . . to probe the workings of the brain in a way that is just not possible currently with natural stimuli,” neuroscientist Venkatesh Murthy of Harvard University who was not involved with the study writes in an email to The Scientist.

A fundamental goal of neuroscience is to understand how a stimulus—a sight, sound, taste, touch, or smell—is interpreted, or perceived, by the brain. While a large number of studies have shown the various ways in which such stimuli activate brain cells, very little is understood about what these activations actually contribute to perception.

In the case of smell, for example, it is well-known that odorous molecules traveling up the nose bind to receptors on cells that then transmit signals along their axons to bundles of nerve endings—glomeruli—in a brain area called the olfactory bulb. A single molecule can cause a whole array of different glomeruli to fire in quick succession, explains neurobiologist Kevin Franks of Duke University who also did not participate in the research. And because these activity patterns “have many different spatial and temporal features,” he says, “it is difficult to know which of those features is actually most relevant [for perception].”

To find out, neuroscientist Dmitry Rinberg of New York University and colleagues bypassed the nose entirely. “The clever part of their approach is to gain direct control of these neurons with light, rather than by sending odors up the animal’s nose,” Caltech neurobiologist Markus Meister, who was not involved in the work, writes in an email to The Scientist.

The team used mice genetically engineered to produce light-sensitive ion channels in their olfactory bulb cells. They then used precisely focused lasers to activate a specific pattern of glomeruli in the region of the bulb closest to the top of the animal’s head, through a surgically implanted window in the skull. The mice were trained to associate this activation pattern with a reward—water, delivered via a lick-tube. The same mice did not associate random activation patterns with the reward, suggesting they had learned to distinguish the reward-associated pattern, or synthetic smell, from others.

Although the activation patterns were not based on any particular odors, they were designed to be as life-like as possible. For example, the glomeruli were activated one after the other within the space of 300 milliseconds from the time at which the mouse sniffed—detected by a sensor. “But, I’ll be honest with you, I have no idea if it stinks [or] it is pleasant” for the mouse, Rinberg says.

Once the mice were thoroughly trained, the team made methodical alterations to the activity pattern—changing the order in which the glomeruli were activated, switching out individual activation sites for alternatives, and changing the timing of the activation relative to the sniff. They tried “hundreds of different combinations,” Rinberg says. He likened it to altering the notes in a tune. “If you change the notes, or the timing of the notes, does the song remain the same?” he asks. That is, would the mice still be able to recognize the induced scent?

From these experiments, a general picture emerged: alterations to the earliest-activated regions caused the most significant impairment to the animal’s ability to recognize the scent. “What they showed is that, even though an odor will [induce] a very complex pattern of activity, really it is just the earliest inputs, the first few glomeruli that are activated that are really important for perception,” says Franks.

Rinberg says he thinks these early glomeruli most likely represent the receptors to which an odorant binds most strongly.

With these insights into the importance of glomeruli firing times for scent recognition, “the obvious next question,” says Franks, is to go deeper into the brain to where the olfactory bulb neurons project and ask, “ How does the cortex make sense of this?”

E. Chong et al., “Manipulating synthetic optogenetic odors reveals the coding logic of olfactory perception,” Science, 368:eaba2357, 2020.–BMhsu532UL56qwtB0yErPYlgoFTIZWsNouvTV9pnT1ikTw6CvyIPyun3rPGdciV29we7ugRVWYc1uuBDh5CN_F-0FzA&utm_content=89854591&utm_source=hs_email

by Ruth Williams

The brains of people in vegetative, partially conscious, or fully conscious states have differing profiles of activity as revealed by functional magnetic resonance imaging (fMRI), according to a report today (February 6) in Science Advances. The results of the study indicate that, compared with patients lacking consciousness, the brains of healthy individuals exhibit highly dynamic and complex connectivity.

“This new study provides a substantial advance in characterizing the ‘fingerprints’ of consciousness in the brain” Anil Seth, a neuroscientist at the University of Sussex, UK, who was not involved in the project, writes in an email to The Scientist. “It opens new doors to determining conscious states—or their absence—in a range of different conditions.”

A person can lose consciousness temporarily, such as during sleep or anesthesia, or more permanently as is the case with certain brain injuries. But while unconsciousness manifests behaviorally as a failure to respond to stimuli, such behavior is not necessarily the result of unconsciousness.

Some seemingly unresponsive patients, for example, can display brain activities similar to those of fully conscious individuals when asked to imagine performing a physical task such as playing tennis. Such a mental response in the absence of physical feedback is a condition known as cognitive-motor dissociation.

Researchers are therefore attempting to build a better picture of what is happening in the human brain during consciousness and unconsciousness. In some studies, electroencephalography (EEG) recordings of the brain’s electrical activities during sleep, under anesthesia, or after brain injury have revealed patterns of brain waves associated with consciousness. But, says Jacobo Sitt of the Institute of Brain and Spinal Cord in Paris, such measurements do not provide good spatial information about brain activity. With fMRI, on the other hand, “we know where the activity is coming from.”

Sitt and colleagues performed fMRI brain scans on a total of 47 healthy individuals and 78 patients who either had unresponsive wakefulness syndrome (UWS)—a vegetative state in which the patient’s eyes open, but they never exhibit voluntary movement—or were in a minimally conscious state (MCS)—having more complex behaviors, such as the ability to follow an object with their eyes, but remaining unable to communicate thoughts or feelings. The scans were performed by an international team of collaborators at three different facilities in Paris, New York, and Liège, Belgium.

Data from the fMRI scans, which generated roughly 400 images in approximately 20 minutes for each patient, was computationally analyzed for identifiable patterns of activity. Four patterns were reproducibly detected within the data from each facility. And, for two of these patterns, the likelihood of their occurrence in a given individual’s scan depended on diagnosis.

Healthy individuals, for example, were more likely than patients to display pattern 1—characterized by high spatial complexity and interregional connectivity indicating brain-wide coordination. Patients with UWS, on the other hand, rarely displayed pattern 1, most often displaying pattern 4—characterized by low complexity and reduced interregional connectivity. Generally speaking, MCS patients fell somewhere between. The occurrence of patterns 2 and 3 were equally likely across all groups.

The team went on to analyze a second set of 11 patients at a facility in Ontario, Canada. Again the four distinct patterns were detected within the fMRI images. Six of these patients had UWS and predominantly displayed pattern 4, while the remaining five, who had cognitive-motor dissociation, had higher rates of pattern 1, supporting previous evidence for consciousness in these patients.

With such a mix of patients, facilities, scanners, and researchers, the study “had every possibility of failing,” says neuroscientist Tristan Bekinschtein of the University of Cambridge, UK, who did not participate in the research. However, the results were “brutally consistent,” he says.

Having identifiable signatures of consciousness and unconsciousness might ultimately help doctors and families make difficult decisions about continuing life support for vegetative patients, says anesthesiology researcher Anthony Hudetz of the University of Michigan who was not involved with the work. It might also provide insight into whether particular rehabilitation methods or other treatments are working.

“All that hinges on a better understanding of what goes on in the brains of these patients versus healthy or aware [people],” Hudetz says. To that end, this paper “makes a major step forward.”

A. Demertzi et al., “Human consciousness is supported by dynamic complex patterns of brain signal coordination,” Sci Adv, 5: eaat7603, 2019.

By Ruth Williams

The sun’s ultraviolet (UV) radiation is a major cause of skin cancer, but it offers some health benefits too, such as boosting production of essential vitamin D and improving mood. A recent report in Cell adds enhanced learning and memory to UV’s unexpected benefits.

Researchers have discovered that, in mice, exposure to UV light activates a molecular pathway that increases production of the brain chemical glutamate, heightening the animals’ ability to learn and remember.

“The subject is of strong interest, because it provides additional support for the recently proposed theory of ultraviolet light’s regulation of the brain and central neuroendocrine system,” dermatologist Andrzej Slominski of the University of Alabama who was not involved in the research writes in an email to The Scientist.

“It’s an interesting and timely paper investigating the skin-brain connection,” notes skin scientist Martin Steinhoff of University College Dublin’s Center for Biomedical Engineering who also did not participate in the research. “The authors make an interesting observation linking moderate UV exposure to . . . [production of] the molecule urocanic acid. They hypothesize that this molecule enters the brain, activates glutaminergic neurons through glutamate release, and that memory and learning are increased.”

While the work is “fascinating, very meticulous, and extremely detailed,” says dermatologist David Fisher of Massachusetts General Hospital and Harvard Medical School, “it does not imply that UV is actually good for you. . . . Across the board, for humanity, UV really is dangerous.”

Wei Xiong of the University of Science and Technology of China who led the research did not set out to investigate the effects of UV light on the brain or the skin-brain connection. He stumbled upon his initial finding “almost accidentally,” he explains in an email to The Scientist. Xiong and his colleagues were using a mass spectrometry technique they had recently developed for analyzing the molecular contents of single neurons, when their results revealed the unexpected presence of urocanic acid—a little-known molecule produced in the skin in response to UV light.

“It was a surprise because we checked through all the literature and found no reports of the existence of this small molecule in the central nervous system,” writes Xiong.

With little information to go on, Xiong and his colleagues decided to see whether UV light could also boost levels of urocanic acid in the brain. They exposed shaved mice to a low-dose of UVB—responsible for sunburn in humans—for 2 hours, then performed mass spectrometry on the animals’ individual brain cells. Sure enough, levels of urocanic acid increased in neurons of the animals exposed to the light, but not in those of control animals.

Urocanic acid can absorb UV rays and, as a result, may be able to protect skin against the sun’s harmful effects. But in the liver and other peripheral tissues, the acid is also known to be an intermediate molecule generated in the metabolic pathway that converts histidine to glutamate. Given glutamate’s role in the brain as an excitatory neurotransmitter, Xiong and his colleagues were interested to test whether the observed UV-dependent increase in urocanic acid in neurons might be coupled with increased glutamate production. It was.

Next, the team showed that UV light enhanced electrical transmission between glutaminergic neurons in brain slices taken from animals exposed to UV, but not in those from control animals. This UV-induced effect was prevented when the researchers inhibited activity of the enzyme urocanase, which converts urocanic acid to glutamate, indicating that the acid was indeed the mediator of the UV-induced boost in glutaminergic activity.

Lastly, the team showed that mice exposed to UV performed better in motor learning and recognition memory tasks than their unexposed counterparts. And, as before, treating the animals with a urocanase inhibitor prevented the UV-induced improvements in learning and memory. Administering urocanic acid directly to animals not exposed to ultraviolet light also spurred similar learning and memory improvements to those achieved with UV exposure.

Whether the results obtained in mice, which are nocturnal and rarely see the sun, will hold true in humans is yet to be determined. But, Fisher says, if the results do hold, the finding that urocanic acid alone can enhance learning and memory might suggest “a way to utilize this information to benefit people without exposing them to the damaging effects of UV.”

H. Zhu et al., “Moderate UV exposure enhances learning and memory by promoting a novel glutamate biosynthetic pathway in the brain,” Cell, doi: 10.1016/j.cell.2018.04.014, 2018.