Neuroscientists pinpoint location of fear memory in amygdala

Jan. 27, 2013 ? A rustle of undergrowth in the outback: it's a sound that might make an animal or person stop sharply and be still, in the anticipation of a predator. That "freezing" is part of the fear response, a reaction to a stimulus in the environment and part of the brain's determination of whether to be afraid of it.

A neuroscience group at Cold Spring Harbor Laboratory (CSHL) led by Assistant Professor Bo Li Ph.D., together with collaborator Professor Z. Josh Huang Ph.D., have just released the results of a new study that examines the how fear responses are learned, controlled, and memorized. They show that a particular class of neurons in a subdivision of the amygdala plays an active role in these processes.

Locating fear memory in the amygdala

Previous research had indicated that structures inside the amygdalae, a pair of almond-shaped formations that sit deep within the brain and are known to be involved in emotion and reward-based behavior, may be part of the circuit that controls fear learning and memory. In particular, a region called the central amygdala, or CeA, was thought to be a passive relay for the signals relayed within this circuit.

Li's lab became interested when they observed that neurons in a region of the central amygdala called the lateral subdivision, or CeL, "lit up" in a particular strain of mice while studying this circuit.

"Neuroscientists believed that changes in the strength of the connections onto neurons in the central amygdala must occur for fear memory to be encoded," Li says, "but nobody had been able to actually show this."

This led the team to further probe into the role of these neurons in fear responses and furthermore to ask the question: If the central amygdala stores fear memory, how is that memory trace read out and translated into fear responses?

To examine the behavior of mice undergoing a fear test the team first trained them to respond in a Pavlovian manner to an auditory cue. The mice began to "freeze," a very common fear response, whenever they heard one of the sounds they had been trained to fear.

To study the particular neurons involved, and to understand them in relation to the fear-inducing auditory cue, the CSHL team used a variety of methods. One of these involved delivering a gene that encodes for a light-sensitive protein into the particular neurons Li's group wanted to look at.

By implanting a very thin fiber-optic cable directly into the area containing the photosensitive neurons, the team was able to shine colored laser light with pinpoint accuracy onto the cells, and in this manner activate them. This is a technique known as optogenetics. Any changes in the behavior of the mice in response to the laser were then monitored.

A subset of neurons in the central amygdala controls fear expression

The ability to probe genetically defined groups of neurons was vital because there are two sets of neurons important in fear-learning and memory processes. The difference between them, the team learned, was in their release of message-carrying neurotransmitters into the spaces called synapses between neurons. In one subset of neurons, neurotransmitter release was enhanced; in another it was diminished. If measurements had been taken across the total cell population in the central amygdala, neurotransmitter levels from these two distinct sets of neurons would have been averaged out, and thus would not have been detected.

Li's group found that fear conditioning induced experience-dependent changes in the release of neurotransmitters in excitatory synapses that connect with inhibitory neurons -- neurons that suppress the activity of other neurons -- in the central amygdala. These changes in the strength of neuronal connections are known as synaptic plasticity.

Particularly important in this process, the team discovered, were somatostatin-positive (SOM+) neurons. Somatostatin is a hormone that affects neurotransmitter release. Li and colleagues found that fear-memory formation was impaired when they prevent the activation of SOM+ neurons.

SOM+ neurons are necessary for recall of fear memories, the team also found. Indeed, the activity of these neurons alone proved sufficient to drive fear responses. Thus, instead of being a passive relay for the signals driving fear learning and responses in mice, the team's work demonstrates that the central amygdala is an active component, and is driven by input from the lateral amygdala, to which it is connected.

"We find that the fear memory in the central amygdala can modify the circuit in a way that translates into action -- or what we call the fear response," explains Li.

In the future Li's group will try to obtain a better understanding of how these processes may be altered in post-traumatic stress disorder (PTSD) and other disorders involving abnormal fear learning. One important goal is to develop pharmacological interventions for such disorders.

Li says more research is needed, but is hopeful that with the discovery of specific cellular markers and techniques such as optogenetics, a breakthrough can be made.

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Story Source:

The above story is reprinted from materials provided by Cold Spring Harbor Laboratory.

Note: Materials may be edited for content and length. For further information, please contact the source cited above.

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Journal Reference:

1. Haohong Li, Mario A Penzo, Hiroki Taniguchi, Charles D Kopec, Z Josh Huang, Bo Li. Experience-dependent modification of a central amygdala fear circuit. Nature Neuroscience, 2013; DOI: 10.1038/nn.3322

Note: If no author is given, the source is cited instead.

Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of ScienceDaily or its staff.

Source: http://feeds.sciencedaily.com/~r/sciencedaily/top_news/~3/lxzF37HaE7w/130128104739.htm

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One-step test for mitochondrial diseases

Jan. 28, 2013 ? More powerful gene-sequencing tools have increasingly been uncovering disease secrets in DNA within the cell nucleus. Now a research team is expanding those rapid next-generation sequencing tests to analyze a separate source of DNA -- within the genes inside mitochondria, cellular power plants that, when abnormal, contribute to complex, multisystem diseases.

The study team, headed by a specialist in mitochondrial medicine at The Children's Hospital of Philadelphia (CHOP), adapted next-generation sequencing to simultaneously analyze the whole exome (all the protein-coding DNA) of nuclear genes and the mitochondrial genome. "A first step in developing treatments for a disease is to understand its precise cause," said Marni J. Falk, M.D., the director and attending physician in the Mitochondrial-Genetic Disease Clinic at Children's Hospital. "We have developed a one-step, off-the-shelf tool that analyzes both nuclear and mitochondrial DNA to help evaluate the genetic cause of suspected mitochondrial disease."

Falk and colleagues describe their customized, comprehensive test, which they call the "1:1000 Mito-Plus Whole-Exome" kit, in the journal Discovery Medicine, published Dec. 26, 2012. Her co-corresponding author, biostatistician Xiaowu Gai, Ph.D., now of the Loyola University Stritch School of Medicine, collaborated on developing the test while at Children's Hospital.

While each mitochondrial disease is very rare in the population, hundreds of causes of mitochondrial diseases are known. Some originate in mutations in DNA specific to the mitochondria, tiny structures located outside the cell nucleus, while many other mitochondrial diseases are based in nuclear DNA genes that affect mitochondrial function. The role of mitochondria in human disease has been recognized only since the 1980s, based on pioneering research by Douglas C. Wallace, Ph.D., now at Children's Hospital, and a co-author of the current study.

Many mitochondrial diseases remain poorly understood. One complicating factor is heteroplasmy -- a mixture of mutated and normal mitochondrial genomes within the same cells or tissues. In contrast to conventional gene sequencing, which can detect only heteroplasmic mutations that reach levels of at least 30 to 50 percent, the customized kit has the sensitivity to detect mitochondrial genome mutations present at levels as low as 8 percent. To achieve their results, the study team adapted an existing whole-exome sequencing kit from Agilent Technologies, expanding it to encompass the mitochondrial genome.

The availability of the new kit, said Falk, if used for either clinical or research purposes, may shorten the "diagnostic odyssey" experienced by many patients and families seeking the cause of debilitating and puzzling symptoms. "Many families travel from one specialist to another for years, searching for the cause of their rare disease," she says. Specific treatments are not always available, but identifying their disease cause may be the first step toward discovering treatments.

A second recent study by Falk and colleagues reviews progress in diagnosing mitochondrial disease, through their experience at a single center over a rapidly changing three-year period before whole-exome sequencing was generally available. The retrospective review in Neurotherapeutics, published Dec. 27, 2012, covers 152 child and adult patients evaluated at CHOP's Mitochondrial-Genetics Diagnostic Clinic from 2008 to 2011.

"Before 2005, very few individuals could receive definitive molecular diagnoses for mitochondrial diseases, because of limitations in both knowledge and technology," said Falk. "Since that time, the clinical ability to sequence whole mitochondrial DNA genomes has significantly improved the diagnosis of many mitochondrial disorders."

During the study period covered in the review article, the clinic at CHOP confirmed definite mitochondrial disease in 16 percent of patients and excluded primary mitochondrial disease in 9 percent. While many diagnostic challenges clearly remain, Falk says the advent of massively parallel nuclear exome sequencing is revealing increasingly more of the genes in nuclear DNA that affect mitochondrial function, and the precise genetic disorder in a given patient, even if it is novel or uncommon. She added that molecular genetics is yielding a more nuanced understanding of the cellular pathways underlying symptoms in many mitochondrial disorders. "Those pathways offer potential new targets for treating these disorders," said Falk.

Funding for both studies came from the National Institutes of Health, grant DK082446. The Discovery Medicine study also was funded through a Foerderer Award for Excellence from The Children's Hospital of Philadelphia Research Institute. Co-authors of the Discovery Medicine study included Eric A. Pierce, M.D., Ph.D., and Mark Consugar, M.S., of the Massachusetts Eye and Ear Infirmary; research and development staff from Agilent under the guidance of Emily LeProust, Ph.D.; and other collaborators from CHOP.

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Story Source:

The above story is reprinted from materials provided by Children's Hospital of Philadelphia, via Newswise.

Note: Materials may be edited for content and length. For further information, please contact the source cited above.

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Journal References:

1. Elizabeth McCormick, Emily Place, Marni J. Falk. Molecular Genetic Testing for Mitochondrial Disease: From One Generation to the Next. Neurotherapeutics, 2012; DOI: 10.1007/s13311-012-0174-1
2. Marni J Falk et al. Mitochondrial Disease Genetic Diagnostics: Optimized Whole-Exome Analysis for All MitoCarta Nuclear Genes and the Mitochondrial Genome. Discovery Medicine, 2013

Note: If no author is given, the source is cited instead.

Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of ScienceDaily or its staff.

Source: http://feeds.sciencedaily.com/~r/sciencedaily/most_popular/~3/1fk6Vf99Vs4/130128163336.htm

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Physical stores hold own against online sales - Stuff

FACE TO FACE: Scorpio Books owner Dave Cameron says customers still prefer to buy books at the Riccarton store rather than online

Many quake-displaced Christchurch retailers turned to online sales, took their first foray into Facebook or at the very least beefed up their company websites as a way to keep their businesses alive after the February 2011 quake.

But many also found online selling was no silver bullet.

A new survey of 11,000 people in 11 countries by PricewaterhouseCoopers reveals why.

The report debunks what it calls the 10 myths of multichannel retailing, which include beliefs that social media will soon be an indispensable retail channel, online retail is cannibalising sales in other channels, and physical stores will become simply showrooms in the future.

In fact, social media is not likely to become an important retail channel any time soon, the survey shows.

Seven out of 10 respondents said they never shopped through social media platforms, although nearly 40 per cent of respondents were following their favourite brands or retailers online, up from 33 per cent last year, as brand lovers were using social media as a "warmup" for future online or physical store shopping excursions.

Nick Paulsen, owner of clothing boutique Clash, said the business used social media mainly to develop the brand and personality of the business but it did not equate to sales.

Clash's Facebook page has 1249 "likes" and is focused on personality and style, music and trends.

"Sometimes we post pics [of new products] but we are not putting price points on there.

"I really want to develop a high level of customer service.

"I believe interaction between customers and retail staff members is so important.

A Facebook community took time to grow and was not a quick fix, Paulsen said.

Social media had limited impact on sales so far. "It's not as reactive as people think."

According to the report, other myths are that physical stores will become mainly showrooms in the future, and online sales are cannibalising sales in other channels.

In fact, respondents said although they researched online, they still preferred to buy products at a physical store.

And shoppers were spending more with their favourite multichannel retailers, not just shifting some purchases to a different brand.

For example, 23 per cent of respondents surveyed said they researched consumer electronics online and then went to a store to buy the product, compared with only 2 per cent who did it the other way around.

Clash does not sell items online.

"To me, online shopping is a real trend.

"I believe people want that interaction with a staff member on the shop floor.

"Online shopping doesn't give you that."

Christchurch bookstore Scorpio is holding its own against online competitors.

Scorpio Books co-owner David Cameron said most sales still came from traditional sales at its physical stores.

Scorpio Books has a website and online sales capacity but online sales were only a small part of the business, Cameron said.

"We do have a Facebook page and we put some quirky stuff up there and we get some favourable responses.

"But it is still not a great marketing tool.

"Despite all the hype about new technology, there is still strong demand for a range of titles that people can come and inspect at their leisure."

Cameron said he expected the trend of online sales would continue to grow but for now online sales were a "relatively tiny" part of overall sales.

After the February 2011 earthquake he had thought the company might have to push online sales but once the business established itself in Riccarton, it had not been necessary.

"The bricks-and-mortar sales have kept up with what we were doing in town, which was a good surprise."

Savoir Lingerie and Swimwear owner Kirsten Billcliff does not place much faith in selling online or using social media to drive sales.

Billcliff said the Merivale swimwear and lingerie boutique used its website to provide customers with information but did not offer online sales because it wanted to maintain relationships with customers.

"We do have Twitter and Facebook. Twitter I barely use at all, and Facebook I use . . . as a medium to keep customers up to date with the latest arrivals in stock," Billcliff said.

"It's about having a relationship with a retailer.

"And specifically, lingerie - it is one of those particular purchases that can't effectively be done online.

"A lot of women are left fairly dissatisfied with online purchases."

Facebook was great for things like getting information out quickly but the business did not "push it".

"We work on the basis our customers are busy, intelligent people. We don't consider our business the be-all and end-all in anybody's life.

"People don't need to spend more time sat at a computer."

Since the earthquakes, customers were doing a lot more pre-purchase research on Savoir's website before coming into the store, because it was harder to get around town since the earthquakes.

Billcliff had improved Savoir's website gallery so customers could have a look online and then come into the store.

However, other Christchurch retailers are reporting strong growth in online sales, include gift and homewares retailer Redcurrent, fashion retailer Lynn Woods and larger companies such as outdoor gear retailer Kathmandu, department store chain Smiths City and clothing retailer Hallenstein Glasson.

And for Christchurch confectionery business The Fudge Cottage, online sales are growing and are likely to be a major part of the business's revenue stream before too long.

The Fudge Cottage managing director Kevin Burns said that after the business was forced to leave its central Arts Centre premises and move to the Bishopdale Mall, the business had become a bit isolated from its central-city customers.

To "fill the gap" created by less foot traffic in between special occasions and seasonal events, and to reconnect with former customers, Burns invested in a responsive, shopper-friendly website designed by Christchurch web design company LeftClick.

Internet orders are already about 10 per cent of total sales, and the business is looking to grow that.

It has a wide network of customers overseas and elsewhere in New Zealand and it has just had its first direct order from Australia.

MULTICHANNEL RETAILING MYTHS OF MULTICHANNEL RETAILING:

? Social media will soon become an indispensable retail channel. On its own, social media isn't likely to become an important retail channel any time soon.

? Physical stores will become mainly showrooms in the future. Many multichannel shoppers research online, but more still prefer to buy at a physical store.

? The tablet will soon overtake the PC as the preferred online shopping device. Shoppers are still overwhelmingly using their PCs to shop online.

? As the world gets smaller, global consumers are becoming more alike. A wide range of local differences in consumer behaviours exists.

? China is the future model of online retail. China is leading in some key trends, but its multichannel and online model is unique.

? Domestic retailers will always have a "home field" advantage over global retailers.. Foreign retailers are making inroads into consumers' lists of favourite multichannel retailers.

? Global online players such as Amazon and eBay will always have a scale advantage over local online players. Many domestic pure players are holding their own.

? Retailers are better positioned than brands because they are closest to the customer. Consumers are shopping directly from manufacturers and many no longer distinguish between retailers and favourite brands.

? Online retail is cannibalising sales in other channels. Consumers are actually spending more with their favourite multichannel retailers, not just shifting some purchases to a different channel.

? Low price is the main driver of customer spending at favourite retailers.Customers value quality, innovative brands over price.

Source: PricewaterhouseCoopers

- ? Fairfax NZ News

Source: http://www.stuff.co.nz/business/8229759/Physical-stores-hold-own-against-online-sales

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Addiction and fear - Alcohol - Addiction Blog

Many people who deal with addiction have a difficult time in managing their fears when they are in recovery. Remember that alcohol and drugs will do nothing in the long run in fixing your problems. It will just make things worse. Managing your fear and anxieties as well as seeking addiction and depression help will take some hard work. ? In fact, addiction and psychological treatment are complementary. Be patient, persistent and stay committed in trying to solve your problem.

Here are a few tips on how an addict can manage their fears and cope with anxiety self help while they are trying to get better.

1. Take it ?One Day At A Time?

Instead of worrying about how you will get through the rest of the week or coming month, try to focus on today. Each day can provide us with different opportunities to learn new things and that includes learning how to deal with your problems. Focus on the present and stop trying to predict what may happen next week. Next week will take care of itself.

2. Manage negative thoughts

A good way to manage your worry is to challenge your negative thinking with positive statements and realistic thinking. When encountering thoughts that make your fearful or anxious, challenge those thoughts by asking yourself questions that will maintain objectivity and common sense.

3. Learn from fearful experiences

In every fear related situation you experience, begin to learn what works, what doesn?t work, and what you need to improve on in managing your fears and anxieties. This will give you the confidence to manage your anxiety the next time around.

4. Take it easy and go at your own pace

Be smart in how you deal with your fears and anxieties. Do not try to tackle everything all at once. When facing a current or upcoming task that overwhelms you with a lot of anxiety, break the task into a series of smaller steps. Completing these smaller tasks one at a time will make the stress more manageable and increases your chances of success. Remember to take things one step at a time and do no more than what you can handle.

5. Use the help that is available

If you have trouble, talk to a member of the clergy, a professional clinical counselor, psychiatrist or psychologist to help deal with fears and anxieties. They will be able to provide you with additional advice and insights on how to cope with your current problem. By talking to a professional, you help yourself in the long run ly learning techniques and behaviors to continue throughout your life. The important thing is to get the proper help by seeing a mental healthprofessional.

Photo credit: stuant63

Source: http://alcohol.addictionblog.org/addiction-and-fear-5-ways-to-address-fear-in-addiction-recovery/

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All This, and Heaven Too

Friends, lovers and foes are established amidst a tragic plane crash. Set on an island somewhere in the middle of the Pacific ocean, the survivors must band together and create a bond much stronger than anything they have ever known. ((closed for now))

Owner:

Game Masters:

This topic is an Out Of Character part of the roleplay, ?All This, and Heaven Too?. Anything posted here will also show up there.

Topic Tags:

Forum for completely Out of Character (OOC) discussion, based around whatever is happening In Character (IC). Discuss plans, storylines, and events; Recruit for your roleplaying game, or find a GM for your playergroup.

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Hello any creepers :) if any of you have questions about the plot or the setting itself, please post here!! I'm excited to finish the plots and characters so you can all have a splendid time!

Also, if this generates more interest, I will be adding more characters and plots :)

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Dodge to Add Bigger Engine for 2013 Dart ... - Automotive Blogs

Despite being miles ahead of the Dodge Caliber it replaced, the 2013 Dodge Dart still hasn?t gotten the respect it deserves. Having sold 25,303 units from July 2012 through December, it pales in comparison to the 2012 Honda Civic?s 217,000 over the whole year?and up until the Civic received its upgrades for 2013, the Dart was the better car.

Alas, it?s not does as well as Chrysler would have liked, so the brand is switching up strategies with it. For 2013, Dodge will be launching a new 2.4-liter four-cylinder engine that?ll be higher up the ladder than the current turbocharged 1.4-liter MultiAir engine. As a result, the small turbo engine will be reeled in, with Dodge cutting a shift for it on the production line to make room for the bigger mill.

It is expected that the 2.4 will eventually find a place paired with the new nine-speed automatic transmission that Chrysler announced for use in the Dodge Dart, Jeep Liberty replacement, and next-generation Chrysler 200 sedan. It may not come immediately, though, as the newest vehicles will be the biggest priority.

To keep the 2013 Dodge Dart fresh as it enters into its first full model year, the automaker is also introducing a Mopar edition at next month?s Chicago Auto Show. Mopar, short for Motor Parts, is Chrysler?s factory-backed division that?ll help you deck out your Chrysler product any which way you like.

?This vehicle is the perfect canvas for personalization and customization,? said Pietro Gorlier, President and CEO of Mopar, Chrysler Group LLC?s service, parts and customer-care brand, in a statement about the car. ?We couldn?t wait to get our hands on it and give it the Mopar treatment.?

While we?ve not yet seen it, we know that it?ll follow along the same lines as the Dodge Challenger, Charger, and Chrysler 300 Mopar editions that have come before it. Chrysler has shown that it will come with blue leather seats. Because the red leather seats it sells in other cars just isn?t outlandish enough.

Overall, when we drove the 2013 Dodge Dart, we were impressed with its level of sophistication and quality materials, but were let down by its loud, coarse 1.4-liter engine and jolting six-speed dual-clutch automatic, feeling it was a bit pokey and unrefined. We hope the upgrades Chrysler is planning fix the problems it has.

Sources: Detroit Free Press, Chrysler

Source: http://blogs.automotive.com/chrysler-to-produce-bigger-engine-for-2013-dodge-dart-downplay-turbo-engine-and-introduce-mopar-edition-125745.html

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A Thought I Had Today

Do you ever feel like the space between point A and point B seems too far apart?

I happened across this picture and started thinking about our choices in life.

We find ourselves staring down the long hallway of options.

Sometimes we run down the hall without interruption.

Other times we stumble on the carpet and find ourselves rolling

around aimlessly with no sense of direction or balance!

We can look up and see the EXIT sign halfway in between where we stand

and where we want to be.

This is when we must decide.

Are we going to quietly place one foot in front of the other while we reflect on our situation

OR

are we going to unabashedly, noisily, and boldly take the

Emergency EXIT

all the way to a new beginning?

What do you do when you find yourself ambling along with the same ol? situation?

Are you steadfast, never changing direction

OR

Are you constantly seeking a different destination?

?

?

?

?

?Call 404-788-2581 to schedule your next home inspection service. Visit our website at http://www.ihihomeinspections.com

??? Make sure that you get a thorough home inspection in Atlanta, GA from the home inspector Atlanta, GA, David Lelak of IHI Home Inspections, serving Atlanta and all of North Georgia. Call us today at 404-788-2581 for a thorough home inspection in Atlanta. We won?t let you buy the money pit.?

?

Source: http://activerain.com/blogsview/3598551/a-thought-i-had-today

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