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Two studies led by UT Southwestern researchers shed new light on how the brain encodes time and place into memories. The findings, published recently in PNAS and Science, not only add to the body of fundamental research on memory, but could eventually provide the basis for new treatments to combat memory loss from conditions such as traumatic brain injury or Alzheimer’s disease.
About a decade ago, a group of neurons known as “time cells” was discovered in rats. These cells appear to play a unique role in recording when events take place, allowing the brain to correctly mark the order of what happens in an episodic memory.
Located in the brain’s hippocampus, these cells show a characteristic activity pattern while the animals are encoding and recalling events, explains Bradley Lega, M.D., associate professor of neurological surgery at UTSW and senior author of the PNAS study. By firing in a reproducible sequence, they allow the brain to organize when events happen, Lega says. The timing of their firing is controlled by 5 Hz brain waves, called theta oscillations, in a process known as precession.
Lega investigated whether humans also have time cells by using a memory task that makes strong demands on time-related information. Lega and his colleagues recruited volunteers from the Epilepsy Monitoring Unit at UT Southwestern’s Peter O’Donnell Jr. Brain Institute, where epilepsy patients stay for several days before surgery to remove damaged parts of their brains that spark seizures. Electrodes implanted in these patients’ brains help their surgeons precisely identify the seizure foci and also provide valuable information on the brain’s inner workings, Lega says.
While recording electrical activity from the hippocampus in 27 volunteers’ brains, the researchers had them do “free recall” tasks that involved reading a list of 12 words for 30 seconds, doing a short math problem to distract them from rehearsing the lists, and then recalling as many words from the list as possible for the next 30 seconds. This task requires associating each word with a segment of time (the list it was on), which allowed Lega and his team to look for time cells. What the team found was exciting: Not only did they identify a robust population of time cells, but the firing of these cells predicted how well individuals were able to link words together in time (a phenomenon called temporal clustering). Finally, these cells appear to exhibit phase precession in humans, as predicted.
“For years scientists have proposed that time cells are like the glue that holds together memories of events in our lives,” according to Lega. “This finding specifically supports that idea in an elegant way.”
In the second study in Science, Brad Pfeiffer, Ph.D., assistant professor of neuroscience, led a team investigating place cells — a population of hippocampal cells in both animals and humans that records where events occur. Researchers have long known that as animals travel a path they’ve been on before, neurons encoding different locations along the path will fire in sequence much like time cells fire in the order of temporal events, Pfeiffer explains. In addition, while rats are actively exploring an environment, place cells are further organized into “mini-sequences” that represent a virtual sweep of locations ahead of the rat. These radar-like sweeps happen roughly 8-10 times per second and are thought to be a brain mechanism for predicting immediately upcoming events or outcomes.
Prior to this study, it was known that when rats stopped running, place cells would often reactivate in long sequences that appeared to replay the rat’s prior experience in the reverse. While these “reverse replay” events were known to be important for memory formation, it was unclear how the hippocampus was able to produce such sequences. Indeed, considerable work had indicated that experience should strengthen forward, “look ahead” sequences but weaken reverse replay events.
To determine how these backward and forward memories work together, Pfeiffer and his colleagues placed electrodes in the hippocampi of rats, then allowed them to explore two different places: a square arena and a long, straight track. To encourage them to move through these spaces, they placed wells with chocolate milk at various places. They then analyzed the animals’ place cell activity to see how it corresponded to their locations.
Particular neurons fired as the rats wandered through these spaces, encoding information on place. These same neurons fired in the same sequence as the rats retraced their paths, and periodically fired in reverse as they completed different legs of their journeys. However, taking a closer look at the data, the researchers found something new: As the rats moved through these spaces, their neurons not only exhibited forward, predictive mini-sequences, but also backward, retrospective mini-sequences. The forward and backward sequences alternated with each other, each taking only a few dozen milliseconds to complete.
“While these animals were moving forward, their brains were constantly switching between expecting what would happen next and recalling what just happened, all within fraction-of-a-second timeframes,” Pfeiffer says.
Pfeiffer and his team are currently studying what inputs these cells are receiving from other parts of the brain that cause them to act in these forward or reverse patterns. In theory, he says, it might be possible to hijack this system to help the brain recall where an event happened with more fidelity. Similarly, adds Lega, stimulation techniques might eventually be able to mimic the precise patterning of time cells to help people more accurately remember temporal sequences of events. Further studies with “In the past few decades, there’s been an explosion in new findings about memory,” he adds. “The distance between fundamental discoveries in animals and how they can help people is becoming much shorter now.”
A collaborative research team, including Los Alamos National Laboratory, University of Stuttgart (Germany), University of New Mexico, and Sandia National Laboratories, has developed a proton conductor for fuel cells based on polystyrene phosphonic acids that maintain high protonic conductivity up to 200 C without water. They describe the material advance in a paper published this week in Nature Materials. Hydrogen produced from renewable, nuclear, or fossil fuels with carbon capture, utilization, and storage can help to decarbonize industries and provide environmental, energy resilience and flexibility across multiple sectors in the economy. Towards that, fuel cells are a promising technology that converts hydrogen into electricity through an electrochemical process, emitting only water.
“While the commercialization of highly efficient fuel-cell electric vehicles has successfully begun,” said Yu Seung Kim, project leader at Los Alamos, “further technological innovations are needed for the next-generation fuel cell platform evolving towards heavy-duty vehicle applications. One of the technical challenges of current fuel cells is the heat rejection from the exothermic electrochemical reactions of fuel cells.
“We had been struggling to improve the performance of high-temperature membrane fuel cells after we had developed an ion-pair coordinated membrane in 2016,” said Kim. “The ion-pair polymers are good for membrane use, but the high content of phosphoric acid dopants caused electrode poisoning and acid flooding when we used the polymer as an electrode binder.”
In current fuel cells, the heat rejection requirement is met by operating the fuel cell at a high cell voltage. To achieve an efficient fuel-cell powered engine, the operating temperature of fuel cell stacks must increase at least to the engine coolant temperature (100 C).
“We believed that phosphonated polymers would be a good alternative, but previous materials could not be implemented because of undesirable anhydride formation at fuel cell operating temperatures. So we have focused on preparing phosphonated polymers that do not undergo the anhydride formation. Kerres’ team at the University of Stuttgart was able to prepare such materials by introducing fluorine moiety into the polymer. It is exciting that we have now both membrane and ionomeric binder for high-temperature fuel cells,” said Kim.
Ten years ago, Atanasov and Kerres developed a new synthesis for a phosphonated poly(pentafluorostyrene) which consisted of the steps i) polymerization of pentafluorostyrene via radical emulsion polymerization and ii) phosphonation of this polymer by a nucleophilic phosphonation reaction. Surprisingly, this polymer showed a good proton conductivity being higher than Nafion in the temperature range >100°C, and an unexpected excellent chemical and thermal stability of >300°C.
Atanasov and Kerres shared their development with Kim at Los Alamos, whose team in turn developed high-temperature fuel cells to use with the phosphonated polymers. With the integration of membrane electrode assembly with LANL’s ion-pair coordinated membrane (Lee et al. Nature Energy, 1, 16120, 2016), the fuel cells employing the phosphonated polymer exhibited an excellent power density (1.13 W cm-2 under H2/O2 conditions with > 500 h stability at 160 C).
What’s next? “Reaching over 1 W cm-2 power density is a critical milestone that tells us this technology may successfully go to commercialization” said Kim. Currently, the technology is pursuing commercialization through the Department of Energy’s ARPA-E and the Hydrogen and Fuel Cell Technologies Office within the Energy Efficiency and Renewable Energy Office (EERE).
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The peer-reviewed work in the Lancet medical journal confirms the vaccine is ‘safe and protects’.
Margaret Keenan, who turns 91 next week, becomes the first person in the world to get the jab as part of a mass vaccination programme, calling it the “best early birthday present”.
American regulators are yet to approve the vaccine, despite the UK pushing ahead with mass rollout.
What is your relationship with pleasure like?
Do you experience and enjoy pleasure when you’re in the mood for it?
Do you have an addictive relationship with it?
Do you have an on-again, off-again relationship with it?
Does your relationship with pleasure feel healthy, supportive, and fun?
Is your relationship with pleasure simple or complex?
Here’s one of more interesting questions to ask yourself:
Do you trust pleasure?
And here’s another meaningful question:
What kind of relationship would you like to have with pleasure?
Pleasure is just pleasure. In its simplest form, it is pure enjoyment. There is nothing else wrapped into it – no distraction, no addiction, no escapism, no guilt, no shame, no fear, no negative consequences.
This past summer I loved eating delicious peaches – so sweet, juicy, and flavorful. I’d often buy 2-3 boxes at a time because I would eat so many of them. Even when I ate five of them in a day, there were no negative consequences that I could discern. They were simply delicious, and I enjoyed the energy they gave me too. This is a a very uncomplicated form of pleasure, and it’s easy to have a healthy relationship with it.
Last month my wife and I did a 30-day challenge of kissing each other for at least one minute each day. It hardly took any time, it was among the easiest “challenges” ever, and it was pure pleasure for us both. It was a nice daily reminder to kiss just because we enjoy it. It feels good to share tender kisses, playful kisses, and passionate kisses alike. Just one minute of kissing is very emotionally satisfying.
But of course there are other forms of pleasure that can become problematic because they’re wrapped up with some negative qualities like addiction or abuse. Choosing a healthy and pleasurable experience isn’t the same as choosing an unhealthy one.
We can project a lot of neediness onto pleasure. We can want it to play a bigger role for us, such as saving us from our problems or providing a substitute for real human relationships. But projecting such neediness onto pleasure isn’t likely to lead to a healthy relationship with pleasure.
Some people wrap so much angst into various forms of pleasure that they try to fix this by swearing off pleasure altogether. They try to get control over it through abstinence. It isn’t necessary to go this far though, just as it isn’t necessary to swear off all human relationships just because you’ve endured some rough ones. It’s not the pleasure that’s the problem. It’s the neediness and projection you bring to it. Pleasure is fine. It’s your relationship with pleasure that needs some improvement.
Consider instead that you can change your relationship with pleasure by relating to it in a much purer and simpler way. Pleasure isn’t an escape. It isn’t a solution. It isn’t an achievement. It isn’t a source of fear, shame, or guilt.
Pleasure is simply a gift. You open it. You receive it. You enjoy it. You appreciate it. And that’s it.
Don’t make it complicated.
Pleasure is fearless, guiltless, and shameless. If you feel fear, shame, or guilt, it isn’t the pleasure itself that made you feel that way. Enjoyment is just enjoyment.
In 2016 when Rachelle and I spent 30 days in a row going to Disneyland, it was a monthlong deep dive into fun. I found the experience transformational in ways I didn’t expect. I like that Disneyland’s ethos gave us permission to engage with fun in such an immersive way for 10-16 hours per day. That experience was beneficial on multiple levels – good for our relationship, nice to spend so much time outdoors, great for incubating business ideas, 10-12 miles of daily walking, and it led to the launch of Conscious Growth Club about six months later. I was hesitant to do it, but it was one of the best deep dives ever.
You can healthfully engage with many simple forms of pleasure, such as by enjoying a juicy peach or a delightful kiss with a willing (and uninfected!) partner. You don’t have to descend into a complex and perilous relationship with pleasure.
When you engage with different forms of pleasure, pay attention to the relationship. Is it still clean, pure, and simple? Are you still engaging to experience pleasure? Or have made the relationship complicated? Do you feel addicted or compelled to engage? Are some negative consequences occurring such as guilt about wasting time, damage to your health, or feeling ashamed that you violated your values?
If you notice that your relationship with some form of pleasure has grown complicated in undesirable ways, you can transition out of that relationship and reinvest in other forms of pleasure that are simpler and purer.
If you clean up this relationship with pleasure, you can sustainably experience a wide variety of healthy forms of pleasure, which can enrich your life tremendously without dragging you down.
Here’s a good way to frame this from a spiritual perspective:
I invite and intend a lifelong relationship with pleasure that is pure, clean, and healthy – and free of any fear, shame, or guilt.
When you do feel fear, shame, or guilt, trace it back to its source. Figure out where those feelings are coming from. Notice that they aren’t coming from the pleasure itself. They’re coming from somewhere else, like the meaning you’re attaching to the experience or the negative side effects of the particular form of pleasure that you’ve chosen. So then you have an invitation to clean up this relationship. Cleanse it. Elevate it. Purify it.
Let your relationship with pleasure be a clean, pure, and healthy gift.
Trials are being planned in the UK to see if combining Covid vaccines might give the best protection.
Researchers at Karolinska Institutet in Sweden have come one step closer toward understanding why some people become seriously ill or die from a common bacterium that leaves most people unharmed. In a study published in The Lancet Microbe, the researchers linked RNA mutations within the bacterium Neisseria meningitidis to invasive meningococcal disease, marking the first time a non-coding RNA in a bacterium has been linked to disease progression.
The researchers have also designed and validated a PCR test that can detect these mutations.
“We found that non-coding RNA mutations within the bacterium N. meningitidis are almost twice as likely to be associated with serious meningococcal disease, an uncommon but serious infection that can lead to death,” says Edmund Loh, corresponding author and assistant professor at the Department of Microbiology, Tumor and Cell Biology at Karolinska Institutet. “This is also the first time a non-coding RNA in a bacterium has been associated with the development of a disease in humans.”
N. meningitidis is a bacterium that is often found in the nose of 10 to 15 percent of the human population. In general, the bacteria do not cause any disease. However, when it does, people can become very ill rapidly and die within a few hours if left untreated.
The research work began in 2017 after a strain of the N. meningitidis bacterium was isolated from a Swedish teenager who succumbed to meningococcal meningitis. When compared with another strain of the same bacterium isolated from an asymptomatic individual, the researchers discovered mutation in a regulatory non-coding RNA molecule, known as RNA thermosensor, or RNAT, within the strain from the deceased teenager.
This finding prompted the researchers to embark on a quest to collect and investigate more than 7,000 RNAT configurations of N. meningitidis from around Europe. In total, the researchers discovered five new variants of RNATs that could be linked to illness, that is they were more likely to appear in individuals who had become ill from the bacterium.
These variants shared a common trait in that they produced more and bigger capsules that insulated the bacterium and thus helped it evade the body’s immune system.
“This is the first time we have been able to associate an RNAT’s effect on meningitis disease progression,” says the paper’s first author Jens Karlsson, PhD student at the same department. “This supports further research into this and other non-coding RNAs’ potential involvement in the development of bacterial diseases.”
As part of the study, the researchers also developed a quick PCR test that is capable of distinguishing these RNAT mutations.
“In the future, this PCR test may be coupled with a simple nose swab at a clinic, and in doing so, facilitate a speedy identification of these mutations, and subsequent treatment,” Edmund Loh concludes.
The study was funded by the Swedish Foundation for Strategic Research, the Knut and Alice Wallenberg Foundation and the Swedish Research Council.
Facts about RNAs:
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In a new study published today in the Proceedings of the National Academy of Sciences, a research team co-led by the University of Minnesota, examined the risks to human well-being and prosperity stemming from ongoing environmental degradation.
“There are many ways that nature provides benefits to people — from the production of material goods to non-material benefits, and the benefits of natural ecology that regulate environmental conditions,” said Kate Brauman, lead author and a lead scientist at the U of M Institute on the Environment (IonE). “We are in a much better position to identify the problems in the way we are managing nature, and that gives us a path forward to manage it better.”
The study looked at a variety of peer-reviewed papers addressing wide-ranging elements of trends in nature and associated impacts on people. The study found that: global declines in most of nature’s contributions to people over the past 50 years, such as natural regulations of water pollutants; negative impacts on people’s well-being are already occurring, including reductions in crop yields from declining pollinator populations and soil productivity and increased exposure to flooding and storms as coastal ecosystems are degraded; and understanding and tracking nature’s contributions to people provides critical feedback that can improve our ability to manage earth systems effectively, equitably and sustainably.
“This paper highlights the value of nature’s contributions to our well-being,” said co-author Steve Polasky, an IonE fellow and a professor in the College of Biological Sciences. “By making these values more visible, we hope that actions are taken to protect nature, so that nature can continue to provide benefits for future generations.”
The work of this study builds from the Intergovernmental Science-Policy Platform on Biodiversity and Ecosystem Services (IPBES) Global Assessment.
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