This colorful graph shows a peak of abnormal epileptic brain activity in
a brain’s hippocampus in which an inhibitory protein called InSyn1 has
been depleted. To test whether this protein was indeed applying ‘brakes’
to brain activity, Duke researchers depleted it in individual neurons,
causing surrounding brain tissue to become overexcited. Credit:
Akiyoshi Uezu, Dan Kanak and Scott Soderling)
In 1959, a scientist named Edward Gray showed that the miniscule gaps
between neurons where chemical messages are sent, called synapses, come
in two main varieties, which researchers later dubbed “excitatory” and
Inhibitory synapses act as the brakes in the brain, preventing it
from becoming overexcited. Researchers thought they were less
sophisticated than their excitatory counterparts because relatively few
proteins were known to exist at these structures. But a new study by
Duke University scientists, published Sept. 9 in Science, overturns that assumption, uncovering 140 proteins that have never been mapped to inhibitory synapses.
“It’s like these proteins were locked away in a safe for over 50
years, and we believe that our study has cracked open the safe,” said
the study’s senior investigator Scott Soderling, an associate professor
of cell biology and neurobiology at Duke. “And there’s a lot of gems.”
In particular, 27 of these proteins have already been implicated by
genome-wide association studies as having a role in autism, intellectual
disability and epilepsy, Soderling said, suggesting that their
mechanisms at the synapse could provide new avenues to the understanding
and treatment of these disorders.
Synapses are common targets of drugs used to treat brain diseases,
but they are also changed by drugs of abuse. About 40 proteins were
already known to cluster on the inhibitory synapses, which are important
not only for preventing overexcitement, which can trigger seizures, but
also sculpting patterns of brain signals.
“The inhibitory synapse is just as important as the excitatory
synapse, but we didn’t have a good way of purifying the proteins that
were there, so we didn’t understand how it worked,” Soderling said.
In the new study, postdoctoral researcher Akiyoshi Uezu in
Soderling’s group used a relatively recent labeling technique called
BioID, which uses a bacterial enzyme to fish for any nearby proteins and
bind to them irreversibly inside a living mouse. The captured proteins
are then recovered from the tissue and identified using established
methods for characterizing proteins.
The afternoon Soderling and Uezu realized the technique was pulling
new proteins from the inhibitory synapse “we both almost fell out of our
chairs,” Soderling said. “We saw this huge list of these really
exciting proteins that no one had ever seen before.”
Two of the proteins had no known function, and unlike other
proteins, their gene sequences provided no clues. The researchers dubbed
those Inhibitory Synapse 1 (InSyn1) and Inhibitory Synapse 2 (InSyn2).
Depleting InSyn1 levels in individual neurons caused surrounding brain
tissue to become overexcited, suggesting that the protein is crucial for
the normal function of inhibitory synapses.
Most exciting to Soderling was that previous genetics studies had
shown several of the proteins cause an inherited form of epilepsy. The
specific role of the proteins was unknown, however.
“Finding them at the inhibitory synapse really gives us important
insights,” Soderling said. “The hypothesis now is that these mutations
are impairing the ability of neurons to inhibit activity. That’s
something that we’re actively studying.”
In addition, neurons have other structures with incomplete parts
lists of proteins. Soderling’s team is collaborating with other
researchers who are interested in probing these other spots using BioID,
which had been originally developed for cells in the petri dish.
Soderling will post a protocol on his lab’s webpage so that others can
learn how to implement this method in mice.
Lastly, the team plans to explore the role of inhibitory synapses in
the formation of long-term memory, which is enabled by synapses
changing the strength of their connections over time. How inhibitory
connections operate in memory is much less understood than in excitatory
synapses, Soderling said.
Gemma needs to fire them all, why is she employing people who trash talk louis like that
Gemma doesn’t run The Debrief, she works there, she doesn’t employ anyone.
CC: everyone else in my inbox; talking shit about any of the family members is a really effective way to get yourself blocked. I hate what they wrote too, and I hate that it’s associated with the band through Gemma’s link to the publication, but I fail to see how you could, in any way, think this was her fault?
I met you in the middle of the night. Not the literal night of course. You know, one of those times in your life when everything seems black and bleak and cold. The emotional middle of the night if you will. Anyways, that’s where you were when I met you. I remember it dawning on me that, even amongst the vast emptiness, you somehow radiated light. Radiated heat. Like one turn of the embers would ignite you in flames and scorch me from the inside out. I wondered why no one had bothered to poke and prod at the amber coals that resided within you. Ones that evidently still gave room for second life. Why no one had tried to help breathe this fire back into your being. To ignite it. To remind you that you could burn bright and beautifully again and always. I guess everyone was too scared of the darkness. Good thing I’ve always been one for a midnight walk.
This morning I had a half-asleep daydream about Laurent getting terribly injured – particularly his face, also in danger of losing a leg. Paschal had drugged him to the gills on poppy syrup or whatever pain medication they might have, so he was not thinking clearly at all. When Damen came in, he panicked and started crying, begging him not to send him away. That’s what always happened to pets who lost their looks, no matter how doted on they were before.
Damen, horrified, held him and told him he was not a PET to him, that he loved him more than anything in the world and always would, no matter what happened to his face or his body. Laurent kept trying to initiate sex, as if to prove he could still be useful; Damen wouldn’t let him because he was too badly hurt for that, and that just made him more upset. Finally Damen just held him while he cried himself to sleep.
When Laurent woke up he didn’t want to talk about it, but Damen kissed him slowly and gently all over his body and made sure he understood that he would always be beautiful to Damen, that he couldn’t even think about what he would do without Laurent. Laurent was just sarcastic about it all but Damen could feel him trembling, and could feel the moment when he relaxed and finally believed him.
Neither of them would let Paschal give him that medication again.
I had a really bizarre dream where I passed out in my high school and everybody thought I was murdered. Core Wheatley was in my class for some reason and when the police arrived, the first thing they did was straight up deck him and put handcuffs on his handles. Then when I came to, I went to the principal’s office where they were ‘interrogating the murderer’ and I slapped one of the police officers for being a fucking idiot and not checking my pulse to see that I wasn’t dead. When I went to the 'interrogation room’, all I hear is CLANG CLANG CLANG and some very loud crying. So I open the door and see a cop beating up Wheatley with his bare fists. The crying was coming from the cop, who just keeps punching Wheatley despite the fact that he’s literally just punching a ball of steel.
look i’m gonna get sappy right now !!! when i first saw fantastic beast, i never thought i’d love newt scamander as much as i do. once i walked out of the theater, i cried because the movie and he was so perfect ???? i waited a week to make him because i’ve seen so many wonderful newt’s who would definitely play him better than me and i would be too intimidated tbh. but when i made him, everyone was so welcoming and even other newt’s had followed me, usually people who have the same muse as me don’t follow so i was surprised ???? it’s only been four days and i already have more than 100 followers, that has NEVER happened before on any of my blogs, i just want to cry, i love you guys asdfgbnbgfds <3 and i’ve but i love everyone in this fandom so much and you guys are so special.
where cw’s the flash remakes the great brain robbery from justice league unlimited. and barry allen gets his brain switched with eobard thawne (or another member of the legion of doom - maybe merlyn? he could be at last i know who the flash is and he has no clue who barry is…or bring in lex luthor idk). and meets up with evil!leonard snart and actually finds an ally when leonard is intrigued by eobard’s personality switch
meanwhile, eobard is stuck in the pipeline with barry’s body and team flash is trying to find out where barry is because the legion of doom has a super secret hideout
Gray wolves were once thriving in Illinois until about the 1860s when they became completely extinct in the state due to hunting. However, in 2002, a rare sighting of a wolf in nothern Illinois was documented but the wolf was shot and killed. The man who had killed the wolf kept the skull as a prize but was later caught and changed with killing an andangered animal. In 2013 he was to pay a fine of $2,300 What was a rare sighting in 2002, is now a regular sighting in northern Illinois and wolves are starting to make their way a little more south. Joe Kath, of the endangered species manager at Illinois’ Department of Natural Resources, says they are now taking small steps to prepare for the wolf number rise. In the future, most likely not soon, they will need to decide if hunting will be necassary or if they will catch them and release them elsewhere, assuming the wolf numbers grow as expected. I really like wolves and I’m upset that I’ve never seen one in real life but I see coyotes and foxes on a regular basis. So apparently, this is why I’ve never seen a wolf in real life but I’m happy that some justice was brought to the lone wolf and that, in the future, Illinois will a normal habitiat to wolves again.