gabae

Eavesdropping on brain cell chatter

Everything we do — all of our movements, thoughts and feelings – are the result of neurons talking with one another, and recent studies have suggested that some of the conversations might not be all that private. Brain cells known as astrocytes may be listening in on, or even participating in, some of those discussions. But a new mouse study suggests that astrocytes might only be tuning in part of the time — specifically, when the neurons get really excited about something. This research, published in Neuron, was supported by the National Institute of Neurological Disorders and Stroke (NINDS), part of the National Institutes of Health.

For a long time, researchers thought that the star-shaped astrocytes (the name comes from the Greek word for star) were simply support cells for the neurons.

It turns out that these cells have a number of important jobs, including providing nutrients and signaling molecules to neurons, regulating blood flow, and removing brain chemicals called neurotransmitters from the synapse. The synapse is the point of information transfer between two neurons. At this connection point, neurotransmitters are released from one neuron to affect the electrical properties of the other. Long arms of astrocytes are located next to synapses, where they can keep tabs on the conversations going on between neurons.

In recent years, it has been shown that astrocytes may also play a role in neuronal communication. When neurons release neurotransmitters, levels of calcium change within astrocytes. Calcium is critical for many processes, including release of molecules from the cell, and activation of a host of proteins within the cell. The role of this astrocytic calcium signaling for brain function remains a mystery.

In this study, Baljit S. Khakh, Ph.D., of the University of California, Los Angeles and his colleagues wanted to know when astrocytes responded to neuron activity with changes in their internal calcium levels. Using calcium indicator dyes, the researchers were able to image, for the first time, changes in calcium levels in the entire astrocyte. Previously, it was only possible to look at certain areas of the cell at one time, which provided an incomplete picture of what was happening.

Dr. Khakh said one of the most important outcomes of this work was in the methods that were used. “What our use of these calcium indicators shows is that we can image calcium throughout the entire astrocyte. This provides a new set of tools for the research community to use and to extend these findings,” he said.

“There has been intense interest in understanding how astrocytes facilitate communication between neurons, but it is only recently that studies with this level of precision have been possible,” said Edmund Talley, Ph.D., program director at NINDS. “Dr. Khakh’s study is an example of an exciting basic, or fundamental, research project that could have an important contribution to the shifting field of astrocyte biology,” he added.

For these experiments, researchers focused on the mossy fiber pathway, which connects two areas of the hippocampus, the structure involved in learning and memory. “This pathway has a unique architecture and although it has been very well studied, the role of astrocytes in this circuit has not been previously explored. This study provides one of the first really detailed understandings of astrocytes within this particular circuit,” said Dr. Khakh.

Dr. Khakh’s team activated neurons (getting them to release neurotransmitter by a variety of techniques) and then looked for a response in the neighboring astrocyte. As calcium levels rose, the astrocyte would light up quickly. They discovered that two neurotransmitters, glutamate and GABA, triggered the astrocytes to release calcium from their internal stores. Importantly, the researchers discovered that calcium levels increased through the entire astrocyte only if there was a large burst of neurotransmitter being released.

“We found that astrocytes in the mossy fiber pathway do not listen to the constant, millisecond by millisecond synaptic chatter that neurons engage in. Instead, they listen when neurons get excessively excited during bursts of activation,” said Dr. Khakh.

These findings suggest that astrocytes in the mossy fiber system may act as a switch that reacts to large amounts of neuronal activity by raising their levels of calcium. These calcium increases occur over multiple seconds, a relatively long time period compared to that seen in neurons. The spatial extent of the astrocyte calcium increases was also relatively large in comparison to the size of the synapse.

“Astrocytes may be sitting there quietly and when there is excessive activation in the neuronal circuit, they immediately respond with an increase in calcium which we could detect. And the next big question becomes, what they do with that calcium?” said Dr. Khakh.

Dr. Khakh’s results in the mossy fiber system differ from those others have described in other brain regions. This raises the intriguing possibility that astrocytes are not all the same and may serve various roles throughout the brain.

“It would be really interesting and important to find that astrocytes function differently in different areas of the brain, in a circuit-specific manner. This study gives a hint that this might be true,” said Dr. Talley.

GABA!

The next neurotransmitter I will talk about is GABA (gamma-aminobutyric acid). GABA is the primary inhibitory neurotransmitter in the brain, but depending on the receptor type, it can be inhibitory or excitatory. We mainly talk about it’s actions as an inhibitory neurotransmitter, but it’s important to note that it can act as an excitatory one as well, depending on the receptor that it acts upon.

There are two main receptor subtypes for GABA, which are known as GABA-A and GABA-B receptors.  GABA-A receptors are ligand-gated chloride channels.  Hopefully, without further explanation, from my past entries, this makes sense.  If you need a refresher, this means that when GABA interacts with these GABA-A receptors, they undergo a conformational change that opens their “pore” to allow chloride (Cl-) ions to flow through.  Since Cl- is negative, it can hyperpolarize the cell (make it more negative) and make it less likely to fire, in the simplest explanation. 

GABA-B receptors are more complex, as they are those G-protein coupled receptors.  Downstream effects can be to open Cl- channels or K+ channels (since there is more potassium inside the cell, K+ might flow out or even if it does not move, shunt an excitatory signal if it arrives while the channels are open), amongst other things.

Inhibitory actions can be very complex on their own and really help to fine-tune the rest of the brain’s activity.  The image above shows a presynaptic cell below and a postsynaptic neuron above it, as GABA is involved in the hypothalamus/feeding behavior- found in this paper (Richards & Berthoud, 2006).

(ALSO, check out the brand new studio version:
https://gabakulka.bandcamp.com/track/bad-wolf )

I am the Bad Wolf. I create myself. I take the words and I scatter them, in time and space. 

Wiecie, że na trasie gramy nowe piosenki. Trafią dopiero na następną płytę, w przyszłym roku, teraz możecie usłyszeć je wyłącznie na naszych koncertach. Ale ponieważ dziś przypada 50-ta rocznica serialu Doctor Who, który był jedną z inspiracji dla tego utworu, postanowiłam się podzielić nagraniem z koncertu - jutro zniknie i albo uzbroicie się w cierpliwość, albo skorzystacie z możliwości podróży w czasie. To typowy bootleg, nagrany bez żadnej produkcji z konsolety, podczas naszego występu w Gnieźnie. I’m sorry, I’m oh so sorry.
Ściskam!


Gaba Kulka - wokal, piano

Wojtek Traczyk - wokal, kontrabas

Wacław Zimpel - klarnet

Robert Rasz - perkusja

youtube

What’s the best way to document your travels? Through dance of course, which is exactly what Dartmouth College undergrad Jake Gaba did when he danced his way across China.

No sedative necessary: Scientists discover new “sleep node” in the brain

A sleep-promoting circuit located deep in the primitive brainstem has revealed how we fall into deep sleep. Discovered by researchers at Harvard School of Medicine and the University at Buffalo School of Medicine and Biomedical Sciences, this is only the second “sleep node” identified in the mammalian brain whose activity appears to be both necessary and sufficient to produce deep sleep.

Published online in August in Nature Neuroscience, the study demonstrates that fully half of all of the brain’s sleep-promoting activity originates from the parafacial zone (PZ) in the brainstem. The brainstem is a primordial part of the brain that regulates basic functions necessary for survival, such as breathing, blood pressure, heart rate and body temperature.

“The close association of a sleep center with other regions that are critical for life highlights the evolutionary importance of sleep in the brain,” says Caroline E. Bass, assistant professor of Pharmacology and Toxicology in the UB School of Medicine and Biomedical Sciences and a co-author on the paper.

The researchers found that a specific type of neuron in the PZ that makes the neurotransmitter gamma-aminobutyric acid (GABA) is responsible for deep sleep. They used a set of innovative tools to precisely control these neurons remotely, in essence giving them the ability to turn the neurons on and off at will.

 “These new molecular approaches allow unprecedented control over brain function at the cellular level,” says Christelle Ancelet, postdoctoral fellow at Harvard School of Medicine. “Before these tools were developed, we often used ‘electrical stimulation’ to activate a region, but the problem is that doing so stimulates everything the electrode touches and even surrounding areas it didn’t. It was a sledgehammer approach, when what we needed was a scalpel.”

“To get the precision required for these experiments, we introduced a virus into the PZ that expressed a ‘designer’ receptor on GABA neurons only but didn’t otherwise alter brain function,” explains Patrick Fuller, assistant professor at Harvard and senior author on the paper. “When we turned on the GABA neurons in the PZ, the animals quickly fell into a deep sleep without the use of sedatives or sleep aids.”

How these neurons interact in the brain with other sleep and wake-promoting brain regions still need to be studied, the researchers say, but eventually these findings may translate into new medications for treating sleep disorders, including insomnia, and the development of better and safer anesthetics.

“We are at a truly transformative point in neuroscience,” says Bass, “where the use of designer genes gives us unprecedented ability to control the brain. We can now answer fundamental questions of brain function, which have traditionally been beyond our reach, including the ‘why’ of sleep, one of the more enduring mysteries in the neurosciences.”


GABA (Gamma-Aminobutyric acid) is a neurotransmitter in the central nervous system of mammals. GABA’s role changes from excitatory to inhibitory as the brain develops into adulthood. Normally, when a neuron receives an impulse, it will make the signal stronger, an inhibiting neurotransmitter prevents the cell from receiving the impulse, and the signal as a whole is weakened. In mammals, GABA regulates the extent to which neurons in the central nervous system will be stimulated. It plays a role in regulating neuronal excitability throughout the nervous system. In humans, GABA is also directly responsible for the regulation of muscle tone. Even though chemically it is an amino acid, GABA is rarely referred to as such in the scientific or medical communities. The term ‘amino acid,’ used without a qualifier, refers to the alpha amino acids, which GABA is not. GABA is also not incorporated into proteins.

A Sleep Aid Without the Side Effects

Insomniacs desperate for some zzzs may one day have a safer way to get them. Scientists have developed a new sleep medication that has induced sleep in rodents and monkeys without apparently impairing cognition, a potentially dangerous side effect of common sleep aids. The discovery, which originated in work explaining narcolepsy, could lead to a new class of drugs that help people who don’t respond to other treatments.

Between 10% and 15% of Americans chronically struggle with getting to or staying asleep. Many of them turn to sleeping pills for relief, and most are prescribed drugs, such as zolpidem (Ambien) and eszopiclone (Lunesta), that slow down the brain by binding to receptors for GABA, a neurotransmitter that’s involved in mood, cognition, and muscle tone. But because the drugs target GABA indiscriminately, they can also impair cognition, causing amnesia, confusion, and other problems with learning and memory, along with a number of strange sleepwalking behaviors, including wandering, eating, and driving while asleep. This has led many researchers to seek out alternative mechanisms for inducing sleep.

Neuroscientist Jason Uslaner of Merck Research Laboratories in West Point, Pennsylvania, and colleagues decided to tap into the brain’s orexin system. Orexin (also known as hypocretin) is a protein that controls wakefulness and is missing in people with narcolepsy. Past studies successfully induced sleep by inhibiting orexin, but had not looked into its effects on cognition. The researchers developed a new orexin-inhibiting compound called DORA-22 and confirmed that it could induce sleep in rats and rhesus monkeys as effectively as the GABA-modulating drugs.

Then the researchers went about testing the drugs’ effects on the animals’ cognition. They measured the rats’ cognition and memory by assessing the rodents’ ability to recognize objects. They presented the rats with a new object—say, a cone or a sphere—that the rats then sniffed and explored. Then they took the object away for an hour. After that hour, the rats were exposed to a new object and the one they’d already gotten to know; if the rats remembered, they spent less time checking out the familiar object. With the primates, Uslaner’s team tested their ability to match colors on a touchscreen and to pay attention to and identify the origin of a flashing light. In all the cases, the researchers found the GABA-modulating sleeping pills caused both the rats and the primates to respond more slowly and less accurately. Monkeys taking the memory and attention tests, for example, were 20% less accurate on the highest dose of each of the GABA-modulating drugs. But DORA-22 had no such effect on cognition, the team reports today in Science Translational Medicine.

“We were very excited,” Uslaner says. “Folks who take sleep medications need to be able to perform cognitive tasks when they awake, and this [compound] could help them do so without impairment.”

Although DORA-22 has not yet been tested in humans, it holds tremendous promise for helping people suffering from sleep disorders, says Emmanuel Mignot, a sleep researcher with the Stanford University School of Medicine in Palo Alto, California. “This study is encouraging and exciting, because there’s good reason to believe it would work differently from what we’ve used in the past,” says Mignot, who helped discover the link between orexin (or its absence) and narcolepsy. “Not every drug works for everyone, so it’s really, really good news to have a potential new drug on the horizon.”

gabae replied to your postIs it really odd that we put our Christmas tree before December?

I’m not putting up a Christmas tree this year! D’:

what? why? D:

kayburg replied to your postIs it really odd that we put our Christmas tree before December?

lolll i thought it was early too, i’m surprised your tree doesnt dry out by christmas o_o unless you use a fake one. usually we buy the xmas tree like two weeks before cause we’re always late with these things LOL. but whatev, xmas trees are awesome

oho, I wish it was authentic, but alas it is fake lol ;;

I think my parents just want to get the decorating done with so that they don’t have to stress about it during December~ BUT THEY HAVE ME TO DECORATE IT SOOOO

Researchers find drug therapy that could eventually reverse memory decline in seniors

It may seem normal: As we age, we misplace car keys, or can’t remember a name we just learned or a meal we just ordered. But University of Florida researchers say memory trouble doesn’t have to be inevitable, and they’ve found a drug therapy that could potentially reverse this type of memory decline.

The drug can’t yet be used in humans, but the researchers are pursuing compounds that could someday help the population of aging adults who don’t have Alzheimer’s or other dementias but still have trouble remembering day-to-day items. Their findings will be published in today’s (March 5) issue of the Journal of Neuroscience.

The kind of memory responsible for holding information in the mind for short periods of time is called “working memory.” Working memory relies on a balance of chemicals in the brain. The UF study shows this chemical balance tips in older adults, and working memory declines. The reason? It could be because their brains are producing too much of a chemical that slows neural activity.

“Graduate student Cristina Banuelos’ work suggests that cells that normally provide the brake on neural activity are in overdrive in the aged prefrontal cortex,” said researcher Jennifer Bizon, Ph.D., an associate professor in the department of neuroscience and a member of UF’s Evelyn F. & William L. McKnight Brain Institute.

This chemical, an inhibitory brain neurotransmitter called GABA, is essential. Without it, brain cells can become too active, similar to what happens in the brains of people with schizophrenia and epilepsy. A normal level of GABA helps maintain the optimal levels of cell activation, said collaborator Barry Setlow, Ph.D., an associate professor in UF’s departments of psychiatry and neuroscience.

Working memory underlies many mental abilities and is sometimes referred to as the brain’s mental sketchpad, Bizon said. For example, Bizon said, you use your working memory in many everyday activities such as calculating your final bill at the end of dining at a restaurant. Most people can calculate a 15 percent tip and add it to the cost of their meal without pencil and paper. Central to this process is the ability to keep multiple pieces of information in mind for a short duration — such as remembering the cost of your dinner while calculating the amount needed for the tip.

“Almost all higher cognitive processes depend on this fundamental operation,” Bizon said.

To determine the culprit behind working memory decline, the researchers tested the memory of young and aged rats in a “Skinner box.” In the Skinner box, rats had to remember the location of a lever for short periods of up to 30 seconds. The scientists found that while both young and old rats could remember the location of the lever for brief periods of time, as those time periods lengthened, old rats had more difficulty remembering the location of the lever than young rats.

But not all older rats did poorly on the memory test, just as not all older adults have memory problems. The study shows the older brains of some people or rats with no memory problems might compensate for the overactive inhibitory system — they are able to produce fewer GABA receptors and therefore bind less of the inhibitory chemical.

Older rats with memory problems had more GABA receptors. The drug the researchers tested blocked GABA receptors, mimicking the lower number of those receptors that some older rats had naturally and restoring working memory in aged rats to the level of younger rats.

“Modern medicine has done a terrific job of keeping us alive for longer, and now we have to keep up and determine how to maximize the quality of life for seniors,” Bizon said. “A key aspect of that is going to be developing strategies and therapies that can maintain and improve cognitive health.”

GABA actions and ionic plasticity in epilepsy

Concepts of epilepsy, based on a simple change in neuronal excitation/inhibition balance, have subsided in face of recent insights into the large diversity and context-dependence of signaling mechanisms at the molecular, cellular and neuronal network level. GABAergic transmission exerts both seizure-suppressing and seizure-promoting actions. These two roles are prone to short-term and long-term alterations, evident both during epileptogenesis and during individual epileptiform events. The driving force of GABAergic currents is controlled by ion-regulatory molecules such as the neuronal K-Cl cotransporter KCC2 and cytosolic carbonic anhydrases. Accumulating evidence suggests that neuronal ion regulation is highly plastic, thereby contributing to the multiple roles ascribed to GABAergic signaling during epileptogenesis and epilepsy.

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