Researchers at University of California, San Diego School of Medicine have identified a control mechanism for an area of the brain that processes sensory and emotive information that humans experience as “disappointment.”
The discovery of what may effectively be a neurochemical antidote for feeling let-down is reported Sept. 18 in the online edition of Science.
“The idea that some people see the world as a glass half empty has a chemical basis in the brain,” said senior author Roberto Malinow, MD, PhD, professor in the Department of Neurosciences and neurobiology section of the Division of Biological Sciences. “What we have found is a process that may dampen the brain’s sensitivity to negative life events.”
Because people struggling with depression are believed to register negative experiences more strongly than others, the study’s findings have implications for understanding not just why some people have a brain chemistry that predisposes them to depression but also how to treat it.
Specifically, in experiments with rodents, UC San Diego researchers discovered that neurons feeding into a small region above the thalamus known as the lateral habenula (LHb) secrete both a common excitatory neurotransmitter, glutamate, and its opposite, the inhibitory neurotransmitter GABA.
Excitatory neurotransmitters promote neuronal firing while inhibitory ones suppress it, and although glutamate and GABA are among two of the most common neurotransmitters in the mammalian brain, neurons are usually specialists, producing one but not both kinds of chemical messengers.
Indeed, prior to the study, there were only two other systems in the brain where neurons had been observed to co-release excitatory and inhibitory neurotransmitters – in a particular connection in the hippocampus and in the brainstem during development of the brain’s auditory map.
“Our study is one of the first to rigorously document that inhibition can co-exist with excitation in a brain pathway,” said lead author Steven Shabel, a postdoctoral researcher with Department of Neurosciences and neurobiology section of the Division of Biological Sciences. “In our case, that pathway is believed to signal disappointment.”
The LHb is a small node-like structure in the epithalamus region of the brain that is critical for processing a variety of inputs from the basal ganglia, hypothalamus and cerebral cortex and transmitting encoded responses (output) to the brainstem, an ancient part of the brain that mammals share with reptiles.
Experiments with primates have shown that activity in the LHb increases markedly when monkeys are expecting but don’t get a sip of fruit juice or other reward, hence the idea that this region is part of a so-called disappointment pathway.
Proper functioning of the LHb, however, is believed to be important in much more than just disappointment and has been implicated in regulating pain responses and a variety of motivational behaviors. It has also been linked to psychosis.
Depression, in particular, has been linked to hyperactivity of the LHb, but until this study, researchers had little empirical evidence as to how this overstimulation is prevented in healthy individuals given the apparent lack of inhibitory neurons in this region of the brain.
"The take-home of this study is that inhibition in this pathway is coming from an unusual co-release of neurotransmitters into the habenula," Shabel said. Researchers do not know why this region of the brain is controlled in this manner, but one hypothesis is that it allows for a more subtle control of signaling than having two neurons directly counter-acting each other.
Researchers were also able to show that neurons of rodents with aspects of human depression produced less GABA, relative to glutamate. When these animals were given an antidepressant to raise their brain’s serotonin levels, their relative GABA levels increased.
"Our study suggests that one of the ways in which serotonin alleviates depression is by rebalancing the brain’s processing of negative life events vis-à-vis the balance of glutamate and GABA in the habenula," Shabel said. "We may now have a precise neurochemical explanation for why antidepressants make some people more resilient to negative experiences."
Pictured: Basal ganglia neurons (green) feed into the brain and release glutamate (red) and GABA (blue) and sometimes a mix of both neurotransmitters (white).
I’m a ‘V’ kind of guy — Vicks, Vaseline, and Viagra!
That moment when you realize that you’re only on slide 7/35 for a new embryology lecture, and it’s already almost 11pm -_-
There is a very steep learning curve to medicine; the level of knowledge and reasoning expected of you increases exponentially as you progress. One year your tutors will be happy if you can name one answer, the next year people will expect you to name them all in order of incidence.
It can feel like an uphill struggle, and you will find yourself learning (and then forgetting) so many things over and over again. But rest assured, eventually things begin to stick!
Embryology: when the uterus decides to take up origami as its hobby for 9 months.
I’ve recently become fascinated by why tuition costs have risen so much in the last 30 years. I mean…it’s insane, and it doesn’t result in a better education. It turns out, for the most part, that it’s marketing. Universities spending money so that they look better than other universities so they get more and better students so that they can make more money (largely via student loans.)
Student loans mean well, and they’re vital. But the education industry has been economically incentivized by their easy access to raise prices and get more students paying more. Schools that don’t spend lots of money on luxury dorms and top notch sports programs don’t grow…kids don’t go to them because, effectively, it’s the same price for 18 year olds because the loans are available.
We should start a university that costs $3000 per year, but you have to sleep on a cot with six other people in the room. Like Hogwarts.
My parents asked me what I wanted for my upcoming birthday…this is what I came up with:
-A Harry Potter-style time turner
-A box of forever-kittens (puppies would also be acceptable)
-Calorie-free foods (preferably things made with chocolate and Olive Garden)
Or just lots of hugs and a family dinner. PSA for the friends, significant others, and family of med students: hug your med student regularly. Med school can be rough and lonely at times.
Olivia, my eldest daughter, caught measles when she was seven years old. As the illness took its usual course I can remember reading to her often in bed and not feeling particularly alarmed about it. Then one morning, when she was well on the road to recovery, I was sitting on her bed showing her how to fashion little animals out of coloured pipe-cleaners, and when it came to her turn to make one herself, I noticed that her fingers and her mind were not working together and she couldn’t do anything.
“Are you feeling all right?” I asked her.
“I feel all sleepy, ” she said.
In an hour, she was unconscious. In twelve hours she was dead.
The measles had turned into a terrible thing called measles encephalitis and there was nothing the doctors could do to save her.
That was twenty-four years ago in 1962, but even now, if a child with measles happens to develop the same deadly reaction from measles as Olivia did, there would still be nothing the doctors could do to help her.
On the other hand, there is today something that parents can do to make sure that this sort of tragedy does not happen to a child of theirs. They can insist that their child is immunised against measles. I was unable to do that for Olivia in 1962 because in those days a reliable measles vaccine had not been discovered. Today a good and safe vaccine is available to every family and all you have to do is to ask your doctor to administer it.
It is not yet generally accepted that measles can be a dangerous illness.
Believe me, it is. In my opinion parents who now refuse to have their children immunised are putting the lives of those children at risk.
In America, where measles immunisation is compulsory, measles like smallpox, has been virtually wiped out.
Here in Britain, because so many parents refuse, either out of obstinacy or ignorance or fear, to allow their children to be immunised, we still have a hundred thousand cases of measles every year.
Out of those, more than 10,000 will suffer side effects of one kind or another.
At least 10,000 will develop ear or chest infections.
About 20 will die.
LET THAT SINK IN.
Every year around 20 children will die in Britain from measles.
So what about the risks that your children will run from being immunised?
They are almost non-existent. Listen to this. In a district of around 300,000 people, there will be only one child every 250 years who will develop serious side effects from measles immunisation! That is about a million to one chance. I should think there would be more chance of your child choking to death on a chocolate bar than of becoming seriously ill from a measles immunisation.
So what on earth are you worrying about?
It really is almost a crime to allow your child to go unimmunised.
Roald Dahl, 1986
NINETEEN EIGHTY SIX.
roald dahl was calling out the anti-vaccination movement as self indulgent bullshit //thirty god damn years ago//.
And this is only in recent history. I can’t imagine the numbers if we had data all the way back to 1986.
And thanks to anti-vaxxers, measles is back in the United States.
Q:i think i wanted to be a surgeon for the wrong reasons: money, to please my family; but i think i'm staying for the right reasons. i started volunteering at my community hospital and as i was leaving the first day i passed by e.r and realized how incredibly low staffed they were with an overwhelming amount of patients. i think i genuinely want to help those people... is it wrong that i started down this path to please my parents?
Nope. I think it’s great you came around to the right reasons!!
I think it’s a bad thing to say on a journey if you’re doing it for the wrong reasons!! Medicine is not something you can do just for the money or to please your parents. It asks too much of you. You’d be miserable if you didn’t love it!
Lots of times we start things for the wrong reasons—maybe we accept a date with someone because we’re bored but that person turns out to be our future husband/wife. Maybe we move across the country thinking we can escape our problems, but maybe the new city teaches us to grow and accept them instead.
You can start something for the wrong reason and figure out midstream that there are a thousand better reasons to do it. Just stick with those better reasons and you’ll be happy. :)
None of us knew exactly what we were getting into when we started this journey; in fact, even when we qualify we will still have many hard truths to learn about medicine.
We all come into medicine with some preconceptions, and I don’t feel it fair to judge each other for them, especially considering how hard it is to choose wjo you want to be for tge rest of your life when you are young.
What matters is not what got you into medicine, but what keeps you there.
tHIS IS THE YEAR WOMEN FINALLY SAID “FUCK YOU” TO SEXISM
YOU GO , GIRL.
'not that you're the genius'
questioning her intelligence when he has that hair cut in 2014
BAAAAAAAM, for fuck’s sake!!
LET ME TELL YOU SOMETHING ABOUT MAYIM BIALIK.
FOR YEARS AS A KID AND TEEN, SHE BALANCED SCHOOL AND ACTING, NEVER ONCE LETTING HER GRADES DROP OR HER CAREER SUFFER.
SHE GRADUATED HIGH SCHOOL AT THE TOP OF HER CLASS, AND WAS ACCEPTED TO HARVARD AND YALE BUT CHOSE TO GO TO UCLA BECAUSE SHE WANTED TO STAY CLOSE TO HER FAMILY.
SHE EARNED A BACHELORS IN NEUROSCIENCE, HEBREW STUDIES, AND JEWISH STUDIES ALL AT THE SAME TIME.
SHE THEN WENT ON TO GET HER DOCTORATE AND A Ph.D. IN NEUROSCIENCE, WHILE BALANCING AN ACTING CAREER AND MOTHERHOOD.
SHE HAS BEEN THE BUTT OF SO MANY FASHION JOKES AND ANTI-SEMETIC JOKES IN HOLLYWOOD. WHEN PEOPLE SAW HER AS AMY, THEY RIDICULED HER ONLINE.
BUT SHE STUCK WITH IT. BECAUSE SHE IS A BEAUTIFUL AND AMAZING PERSON AND IS HAVING NONE OF THIS “WOMEN CAN’T BE SUCCESSFUL AND SMART BULLSHIT.
SHE IS ALSO A NOW-SINGLE MOM OF TWO BOYS. AND STILL KEEPS HER CAREERS (YES THAT’S FUCKING PLURAL) ACTIVE.
BUT YET, PEOPLE STILL HAVE THE AUDACITY TO ASK HER STUPID FUCKING SEXIST QUESTIONS THAT THEY WOULD NEVER GIVE, SAY, JIM PARSONS OR JOHNNY GALECKI.
MAYIM BIALIK IS A FUCKING ICON.
50 things I learned about med school from med students
I’ve had the chance to talk to different medical student from different schools, both MD and DO, public and private schools, and all other parts of the spectrum.
These are based off things I was told! I haven’t started med school yet, so I can’t actually testify. But I figure with they went through it and had some good advice and things to say, hey why not?
This isn’t exactly as it’s gonna go down. You make your own experiences and will find your own way.
- This is hardest you will have ever done. So far.
- Even though it seems like you have no time, you really do. Now is the time to go to social events and make friends.
- Take pictures with everyone at your white coat ceremony.
- Anatomy has three types of people on the first day; the people who are way too fascinated, the ones who cry because they are cutting open a dead person, and the people who throw up into the slop bucket.
- Always flip the body slowly and with precision. Unless you want a formaldehyde and fat shower.
- You might fail your first test. Cry a lot then get over it.
1. push yourself to get up before the rest of the world - start with 7am, then 6am, then 5:30am. go to the nearest hill with a big coat and a scarf and watch the sun rise.
2. push yourself to fall asleep earlier - start with 11pm, then 10pm, then 9pm. wake up in the morning feeling re-energized and comfortable.
3. get into the habit of cooking yourself a beautiful breakfast. fry tomatoes and mushrooms in real butter and garlic, fry an egg, slice up a fresh avocado and squirt way too much lemon on it. sit and eat it and do nothing else.
4. stretch. start by reaching for the sky as hard as you can, then trying to touch your toes. roll your head. stretch your fingers. stretch everything.
5. buy a 1L water bottle. start with pushing yourself to drink the whole thing in a day, then try drinking it twice.
6. buy a beautiful diary and a beautiful black pen. write down everything you do, including dinner dates, appointments, assignments, coffees, what you need to do that day. no detail is too small.
7. strip your bed of your sheets and empty your underwear draw into the washing machine. put a massive scoop of scented fabric softener in there and wash. make your bed in full.
8. organise your room. fold all your clothes (and bag what you don’t want), clean your mirror, your laptop, vacuum the floor. light a beautiful candle.
9. have a luxurious shower with your favourite music playing. wash your hair, scrub your body, brush your teeth. lather your whole body in moisturiser, get familiar with the part between your toes, your inner thighs, the back of your neck.
10. push yourself to go for a walk. take your headphones, go to the beach and walk. smile at strangers walking the other way and be surprised how many smile back. bring your dog and observe the dog’s behaviour. realise you can learn from your dog.
11. message old friends with personal jokes. reminisce. suggest a catch up soon, even if you don’t follow through. push yourself to follow through.
13. think long and hard about what interests you. crime? sex? boarding school? long-forgotten romance etiquette? find a book about it and read it. there is a book about literally everything.
14. become the person you would ideally fall in love with. let cars merge into your lane when driving. pay double for parking tickets and leave a second one in the machine. stick your tongue out at babies. compliment people on their cute clothes. challenge yourself to not ridicule anyone for a whole day. then two. then a week. walk with a straight posture. look people in the eye. ask people about their story. talk to acquaintances so they become friends.
15. lie in the sunshine. daydream about the life you would lead if failure wasn’t a thing. open your eyes. take small steps to make it happen for you.