ventral tegmental area

The Genes and Neural Circuits Behind Autism’s Impaired Sociability

Researchers at Beth Israel Deaconess Medical Center (BIDMC) have gained new insight into the genetic and neuronal circuit mechanisms that may contribute to impaired sociability in some forms of Autism Spectrum Disorder. Led by Matthew P. Anderson, MD, PhD, Director of Neuropathology at BIDMC, the scientists determined how a gene linked to one common form of autism works in a specific population of brain cells to impair sociability. The research, published in the journal Nature, reveals the neurobiological control of sociability and could represent important first steps toward interventions for patients with autism.

Anderson and colleagues focused on the gene UBE3A, multiple copies of which causes a form of autism in humans (called isodicentric chromosome 15q). Conversely, the lack of this same gene in humans leads to a developmental disorder called Angelman’s syndrome, characterized by increased sociability. In previous work, Anderson’s team demonstrated that mice engineered with extra copies of the UBE3A gene show impaired sociability, as well as heightened repetitive self-grooming and reduced vocalizations with other mice.

“In this study, we wanted to determine where in the brain this social behavior deficit arises and where and how increases of the UBE3A gene repress it,” said Anderson, who is also an Associate Professor in the Program in Neuroscience at Harvard Medical School and Director of Autism BrainNET Boston Node. “We had tools in hand that we built ourselves. We not only introduced the gene into specific brain regions of the mouse, but we could also direct it to specific cell types to test which ones played a role in regulating sociability.”

When Anderson and colleagues compared the brains of the mice engineered to model autism to those of normal – or wild type (WT) – mice, they observed that the increased UBE3A gene copies interacted with nearly 600 other genes. After analyzing and comparing protein interactions between the UBE3A regulated gene and genes altered in human autism, the researchers noticed that increased doses of UBE3A repressed Cerebellin genes.

Cerebellin is a family of genes that physically interact with other autism genes to form glutamatergic synapses, the junctions where neurons communicate with each other via the neurotransmitter glutamate. The researchers chose to focus on one of them, Cerebellin 1 (CBLN1), as the potential mediator of UBE3A’s effects. When they deleted CBLN1 in glutamate neurons, they recreated the same impaired sociability produced by increased UBE3A.
“Selecting Cerebellin 1 out of hundreds of other potential targets was something of a leap of faith,” Anderson said. “When we deleted the gene and were able to reconstitute the social deficits, that was the moment we realized we’d hit the right target. Cerebellin 1 was the gene repressed by UBE3A that seemed to mediate its effects.”

In another series of experiments, Anderson and colleagues demonstrated an even more definitive link between UBE3A and CBLN1. Seizures are a common symptom among people with autism including this genetic form. Seizures themselves when sufficiently severe, also impaired sociability. Anderson’s team suspected this seizure-induced impairment of sociability was the result of repressing the Cerebellin genes. Indeed, the researchers found that deleting UBE3A, upstream from Cerebellin genes, prevented the seizure-induced social impairments and blocked seizures ability to repress CBLN1.

“If you take away UBE3A, seizures can’t repress sociability or Cerebellin,” said Anderson. “The flip side is, if you have just a little extra UBE3A – as a subset of people with autism do – and you combine that with less severe seizures - you can get a full-blown loss of social interactions.”

The researchers next conducted a variety of brain mapping experiments to locate where in the brain these crucial seizure-gene interactions take place.

“We mapped this seat of sociability to a surprising location,“ Anderson explained. Most scientists would have thought they take place in the cortex – the area of the brain where sensory processing and motor commands take place – but, in fact, these interactions take place in the brain stem, in the reward system.”

Then the researchers used their engineered mouse model to confirm the precise location, the ventral tegmental area (VTA), part of the midbrain that plays a role in the reward system and addiction. Anderson and colleagues used chemogenetics – an approach that makes use of modified receptors introduced into neurons that responds to drugs, but not to naturally-occurring neurotransmitters – to switch this specific group of neurons on or off. Turning these neurons on could magnify sociability and rescue seizure and UBE3A-induced sociability deficits.

“We were able to abolish sociability by inhibiting these neurons and we could magnify and prolong sociability by turning them on,” said Anderson. “So we have a toggle switch for sociability. It has a therapeutic flavor; someday, we might be able to translate this into a treatment that will helps patients.”

Playboy - VI

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Genre: Fluff

Word Count: 1671


You had a business lecture that same morning, so when you woke up with 10 minutes to spare, you frantically ran around your room to gather your things, thoughts of the previous night disappearing from your mind.

You grabbed your notebooks and stuffed them into your backpack. You remembered you had work, so you fetched your uniform from your closet and shoved it in with your things before heading out the door.

You rushed into the lecture hall and found your seat just before your professor walked in. You were relieved that he hadn’t caught you, your business professor was incredibly tough on attendance.

When the afternoon rolled around, you walked into your psychology lecture hall and took your seat next to Ella. She was already busy revising her notes and you decided not to bother her. When you finally found the motivation to pay attention, you realised the lecture was about the psychology of love. You cringed and asked the universe why it was doing this to you.

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anonymous asked:

will you write a drabble based on the premiere episode please? :D

I kind of assumed you meant about Omelia, so I went that route. Hope you like it sweets!

When you fall in love with someone, your brain undergoes certain changes. First, there’s the initial rush; the release of dopamine and norepinephrine through the same centers involved in addictions. It accounts for the first wave, the lust and intoxication, the magnetism between trauma surgeon and neurosurgeon, the reason they couldn’t get enough of each other’s taste, of their scent and touch. It was the reason for the intensity and need.

But the thing about excitatory neurotransmitters, of the constant firing of neurons, is that it can’t be sustained for long. That’s why they call it the honeymoon phase, because it always comes to an end. There is always that inevitable fall back into reality, and one of two thing could happen. The love fades, and you move on with your life, or there’s a release of another chemical – sometimes nicknamed the love hormone – oxytocin.

Amelia had felt that initial attraction a few times before, but while she loved before, she wondered at times if maybe her brain had grown barren, a drought of oxytocin. Maybe the parts of her brain needed to sustain that feeling were broken, malfunctioning. For as much as she adored Ryan, as much as she loved James, this was a new sensation; an undying one despite all her best efforts. She was in love with Owen Hunt. 

What is happening?

That question was hardly a new one now. Every time they got in a room together, every time she had but a fleeting thought of the redhead in trauma one, those neurons would fire, blood would rush to her ventral tegmental area, to her nucleus accumbens, and hypothalamus. And suddenly all that mattered in the world was him.

The only problem was she could never tell if these responses were the same in him. If only she could shove him into an MRI and make him listen to her voice, show him pictures of her face, maybe she could see how he felt in return. Because every time she thought she had it sorted out, a new wrench would be thrown into her plan. They were just friends, weren’t they? But there were those looks, those comments, those kisses, that told her otherwise. Except then they would fade and everything would be normal again – until it wasn’t.

What is happening?

Eyes trailed after the former chief from across the trauma bay as he made his way past the nurse’s station and down the hall. Days had passed since their kiss on the porch. Days of awkward smiles and bashful stares but all that was spoken between them was a consult on a potential traumatic brain injury that had turned out to be nothing more than a small bump. It was driving her crazy, this chemical overload, and without release, she might go mad entirely.

Without any conscious thought, a tablet was dropped on the nearest counter and sneakers padded after him, each step increasing in speed until she caught up to him at the door of the attending’s lounge. Slipping inside, without intention, her body blocked the door to prevent exit.

“Hey,” Amelia breathed, offering a smile before realizing she had no idea what exactly she was doing.

He turned to face her, expression mimicking her own and nodded. “Hey.”

Hands behind her back, she fidgeted, forgetting that most people would follow that up with something – more talking, or at least some kind of movement to justify chasing him inside. Instead, she just stared, keeping that same stiff grin plastered to her face.

He froze, concerned. “Can I help you with something?”

“No, I– Um–” Get it together, Shepherd. You’re a world-class neurosurgeon and now you’re standing here like a total dork. Say something. “I just–” There it was, those chemicals interfering with rational thought again. For a neurosurgeon knowing exactly what was happening, she certainly didn’t do very well to handle it. She stepped further in, reaching for an apple off the counter and holding it up. “Apple.” Oh god. Now I sound like I’m in preschool. Yes, Amelia. Apple. Very good. Can you spell ‘apple’ for us?

He nodded again, turning back toward the fridge in search of his own meal. This – this was exactly why it was so confusing. Days before, he had stuttered like her. He had leaned in and kissed her and given her that look. And now he was standing here, pretending like nothing happened.

Azure orbs locked on his every movement and try as she might, the words were lost upon her tongue to find any graceful way of approaching the subject. “Damn it, Owen!”

He straightened himself out, adjusting to properly face her. Baby blues narrowed, lips parting for a second before speaking. “I’m sorry? Did I do something?”

“Yes. No. I mean–” Amelia pouted, folding her arms across her chest. “You kissed me.”

“You seemed to enjoy it.”

“I– That’s not the point. Don’t play dumb. You kissed me and then you left and we never–”

“You were pulled away. I thought it might be weird to spend the night on your porch.”

She shifted her weight, giving him another look to say that’s not what she meant.

Owen exhaled, taking a step toward her. “Amelia…”

“I am– I’m not good at this. I’m not the one who unmixes messages. I’m the one who mixes them.”

“What?”

“What’s happening here? What is this…thing we’re doing? Because sometimes we’re friends and sometimes we’re making out and sometimes… I don’t do well with pretending to feel one way when I actually–”

He was quiet for a moment, bringing his gaze up to lock with hers. There it was, that look in her eye; the one that echoed his own with the fear she so often hid. Owen took a breath, reaching to take her hand in his. Running his finger along the back of her hand, a few beats passed before he allowed himself to respond. “I like you Amelia. I really, really like you. And I don’t know what this is, but I know–” He paused, collecting his thoughts. “I know I want more of it. More of you. I just wasn’t sure if you–”

“I do. I mean, I want that, too. More of you. Whatever that means.”

“It means doing more of this,” he smiled, leaning down to press his lips against hers.

“I like that.”

“And maybe we go out sometimes. I have this concert thing…” he started.

“A concert thing?”

“Ed Sheeran. Two tickets Friday night. I was thinking maybe we could go together if you’re not on-call?”

“I’m not. And I do love Ed Sheeran.” Amelia flashed her cheshire grin. “And the company wouldn’t be so bad, either.”

He chuckled. “The show starts at eight. I’ll pick you up at six, so we can grab a bite first?”

“Yeah, I’d like that. It’ll be nice to have food that isn’t dinosaur chicken nuggets.”

“Damn, there go my plans for the restaurant.”

“Shut up,” she laughed, stepping up onto her toes to steal a kiss. “I’ll see you at six.” 

“See you at six,” he repeated, mimicking her actions with a peck of his own.

“I should go,” she stated, but didn’t bother to even look toward the door.

“Back to work,” he agreed, but it was a moment before either of them budged.

Planting another kiss upon his lips, it took all the energy she had to break the magnetism between them. “Back to work,” she repeated, muttering ‘that way’ under her breath. Maybe that dopamine and norepinephrine response wasn’t lost completely to oxytocin – but whatever this was, she never wanted it to stop.

Hormones that are released during hunger affect decision making

When hungry, the hormone ghrelin is produced in the stomach. In a new study conducted on rats at Sahlgrenska Academy, University of Gothenburg, the hormone has been shown to have a negative effect on decision making capabilities and impulse control.

“For the first time, we have been able to show that increasing ghrelin to levels that are seen prior to meals or during fasting, causes the brain to act impulsively and also affects the ability to make rational decisions,” says Karolina Skibicka, docent at Sahlgrenska Academy, University of Gothenburg.

Impulsivity

Impulsivity is complex, but can be broken down into impulsive action (inability to resist a motoric response) and impulsive choice (inability to delay gratification).

Many have experienced the difficulty of resisting getting a sandwich or something else, even if we know that dinner will be served soon, and the same is true for the rats used in the study.

The rats can be trained to be rewarded (with sugar) when they execute an action such as pressing a lever (“go”) - or instead they can be rewarded only when they resist pressing the lever (“no-go”) when an appropriate learned signal is given. They learn this by repeatedly being given a signal, for example, a flash of light or a buzzing sound that tells them which action should be executed for them to receive their reward.

Were given ghrelin

An inability to resist pressing the lever, when the “no-go” signal is given, is a sign of impulsivity. Researchers found that rats given ghrelin directly into the brain, which mimics how the stomach would notify us of a need to eat, were more likely to press the lever instead of waiting, despite it causing them loose their reward.

The ability to delay gratification in order to get a greater reward later is a comparable measure of impulsive choice (decision). It can be illustrated by options such as those between getting a single cookie now or several cookies if you wait a few minutes, or overeating high-calorie foods for immediate feeling of pleasure while disregarding the long term benefits of eating less or eating healthy.

The person who chooses immediate gratification even though waiting provides a greater reward, is characterized as being more impulsive and that implies a poorer ability to make rational decisions.

Reduced the impulsive behavior 

Researchers at Sahlgrenska Academy found that higher levels of ghrelin prevented the rats from being able to wait for the greater reward. They further evaluated where in the brain ghrelin acts to affect impulsivity.

“Our results showed that restricting ghrelin effects to the ventral tegmental area, the part of the brain that is a crucial component of the reward system, was sufficient to make the rats more impulsive. Importantly, when we blocked ghrelin, the impulsive behavior was greatly reduced,” says Karolina Skibicka.
Even a short period of fasting, a more natural way of increasing the release of ghrelin, increased impulsive behavior.

Long-term changes

Impulsivity is a distinctive feature of many neuropsychiatric disorders and behavior disorders such as ADHD, obsessive compulsive disorder (OCD), autism spectrum disorder (ASD), drug abuse and eating disorders.

The study also showed that increased levels of ghrelin even caused long-term genetic changes in the brain circuits that are linked to impulsivity and decision making. A ghrelin injection into the brain that resulted in impulsive behavior in rats, caused the same type of changes in dopamine related genes and enzymes as can be seen in ADHD and OCD.

“Our results indicate that the ghrelin receptors in the brain can be a possible target for future treatment of psychiatric disorders that are characterized by problems with impulsivity and even eating disorders,” says Karolina Skibicka.

“Our study is conducted on rats, they are an excellent model of impulsive behaviors present in humans, but of course our results should be confirmed in a clinical setting”, says Karolina Skibicka.

The article The Stomach-Derived Hormone Ghrelin Increases Impulsive Behavior was published in the journal, Neuropsychopharmacology in April.

We know we should put the cigarettes away or make use of that gym membership but in the moment, we just don’t do it. There is a cluster of neurons in our brain critical for motivation, though. What if you could hack them to motivate yourself?

These neurons are located in the middle of the brain, in a region called the ventral tegmental area. A paper published Thursday in the journal Neuron suggests that we can activate the region with a little bit of training.

Could You Hack Your Brain To Get More Motivated?

Illustration: Gary Waters/Getty Images/Ikon Images