Time Cells Discovered in the Brain

How does our brain know that “thisfollows “that”? Two people meet, fall in love and live happily ever after—or sometimes not. The sequencing of events that takes place in our head—with one thing coming after another—may have something to do with so-called time cells recently discovered in the human hippocampus. The research provides evidence for how our brain knows the start and end of memories despite time gaps in the middle. As these studies continue, the work could lead to strategies for memory restoration or enhancement.

The research has focused on “episodic memory,” the ability to remember the “what, where and when” of a past experience, such as the recollection of what you did when you woke up today. It is part of an ongoing effort to identify how the organ creates such memories. A team led by Leila Reddy, a neuroscience researcher at the French National Center for Scientific Research, sought to understand how human neurons in the hippocampus represent temporal information during a sequence of learning steps to demystify the functioning of time cells in the brain. In a study published this summer in the Journal of Neuroscience, Reddy and her colleagues found that, to organize distinct moments of experience, human time cells fire at successive moments during each task. The study provided further confirmation that time cells reside in the hippocampus, a key memory processing center. They switch on as events unfold, providing a record of the flow of time in an experience. “These neurons could play an important role in how memories are represented in the brain,” Reddy says. “Understanding the mechanisms for encoding time and memory will be an important area of research.”

Hippocampi, one in each brain hemisphere

Matthew Self, a co-author of the study and a senior researcher in the department of vision and cognition at the Netherlands Institute for Neuroscience, emphasizes the importance of these hippocampal time cells’ role in encoding experiences into memory. “When we recall a memory, we are able to remember not only what happened to us but also where we were and when it happened to us,” he says. “We think that time cells may be the underlying basis for encoding when something happened.”

While researchers have known about the existence of time cells in rodent brains for decades, they were first identified in the human brain late last year by researchers at the University of Texas Southwestern Medical Center and their colleagues. To better understand these cells, Reddy and her team examined the hippocampal activity of patients with epilepsy who had electrodes implanted in their brain to evaluate a possible treatment for their condition. The subjects agreed to participate in two different experiments after their surgery.

During the surgery, the electrodes are inserted through small holes of around two millimeters in the skull. These holes are sealed until the patients recover from the surgery and are monitored for up to two weeks with the electrodes in place in an epilepsy monitoring unit, or EMU,” Self says. “We record the hippocampal neuronal activity while the patients are performing tasks in the EMU for a period of about one week after the surgery.”

In the first experiment, the study participants were presented with a sequence of five to seven pictures of different people or scenes in a predetermined order that was repeated multiple times. A given image, say of a flower, was shown for 1.5 seconds, followed by a half-second pause and then another image—a dog, for instance. In a random 20 percent of the image intervals throughout the sessions, the parade of pictures stopped, and participants had to decide which of two images was the next correct one in the sequence before continuing. The researchers discovered that, over the course of 60 repetitions of the entire sequence, all of the time-sensitive neurons fired at specific moments in intervals between quizzes, no matter which image was shown.

Source: https://www.scientificamerican.com/

How To Starve Cancer Tumors and Beef Up The Immune Cells

Tumors are hogs, gobbling nutrients to fuel their runaway growth, and for decades researchers have tried to develop drugs that cut off their food supply. A study out today shows that an updated version of a failed cancer drug can not only prevent tumor cells from using an essential nutrient, but also spur immune cells to attack the growths.

T lymphocyte cells attacking a cancer cell, computer illustration. T lymphocytes are a type of white blood cell that recognise a specific site (antigen) on the surface of cancer cells or pathogens and bind to it. Some T lymphocytes then signal for other immune system cells to eliminate the cell. The genetic changes that cause a cell to become cancerous lead to the presentation of tumour antigens on the cell’s surface.

It’s a pretty striking paper,” says cancer biologist Ralph DeBerardinis of the University of Texas Southwestern Medical Center in Dallas, who wasn’t connected to the study. “With a single drug, you can in effect starve the tumor and beef up the immune cells.”

Cancer cells eat to obtain molecules vital for survival and replication, but their gluttony also turns their surroundings into an acidic, oxygen-deprived moat that stymies immune cells trying to eliminate them. One of the nutrients many tumors need in abundance is the amino acid glutamine, which provides the building blocks for fabricating molecules such as DNA, proteins, and lipids. “Glutamine is incredibly important for cellular metabolism,” says immunologist Jonathan Powell of the Johns Hopkins School of Medicine in Baltimore, Maryland.

Starting in the 1950s, researchers tried to turn tumors’ glutamine dependence against them, developing drugs to block its metabolism. A bacteria-derived compound called DON, for instance, kills tumors by inhibiting several enzymes that allow cancer cells to use glutamine. In clinical trials, however, the drug provoked severe nausea and vomiting, and it was never approved.

Now, Powell and colleagues have crafted a new version of DON that may be easier to stomach. It carries two chemical groups that keep it inert until it reaches the tumor’s neighborhood. There, enzymes that normally loiter around tumors remove these molecular handcuffs, unleashing the drug on the cancerous cells. With this approach, “the vast majority of the active drug is where we want,” Powell says.

To test their new compound, he and colleagues injected four types of cancer cells into mice, inducing tumors. They then dosed some of the animals with their next-generation DON. The drug worked against all four kinds of tumors, the scientists report today in Science. In untreated mice, for example, colon cancer tumors had grown more than five times larger after about 3 weeks. But in rodents that received DON, the tumors shrank and almost disappeared. The researchers found that the drug wasn’t just throttling glutamine metabolism. It was also disrupting other aspects of the cellsbiochemistry, such as their ability to use the sugar glucose.

Source: https://www.sciencemag.org/

CRISPR Reverses Duchenne Muscular Dystrophy Mutation

CRISPR-Cas9 has, for the first time, been tested by systemic delivery in a large animal—and the results are striking. Working in a dog model of Duchenne muscular dystrophy (DMD), the gene editing not only restored the expression of the protein dystrophin, it also improved muscle histology in the dogs.

Our technology was developed using human cells and mice to correct the same type of mutation as in these dogs. It was critical for us to test gene editing in a large animal because it harbors a mutation analogous to the most common mutation in DMD patients,” said Eric Olson, Ph.D., professor and chair of molecular biology at the University of Texas Southwestern Medical Center and lead author. The researchers wrote that this is “an essential step toward clinical translation of gene editing as a therapeutic strategy for DMD.”

Indeed, Dame Kay E. Davies, Ph.D., professor of anatomy and director of the MRC Functional Genomics Unit at the University of Oxford and a pioneer in the field of DMD research, echoes this sentiment explains, “This is a very exciting paper as it shows that gene editing can be reasonably affective in a large animal model of DMD.”

The paper, “Gene editing restores dystrophin expression in a canine model of Duchenne muscular dystrophy,” appears in the last issue of Science.

Source: https://www.genengnews.com/