neuronal networks

Blue Brain team finds 'Multi-dimensional universe' in brain networks

For most people, it is a stretch of the imagination to understand the world in four dimensions but a new study has discovered structures in the brain with up to eleven dimensions – ground-breaking work that is beginning to reveal the brain’s deepest architectural secrets.

Using algebraic topology in a way that it has never been used before in Neuroscience, a team from the Blue Brain Project has uncovered a universe of multi-dimensional geometrical structures and spaces within the networks of the brain.

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Learning is physical. Learning means the modification, growth, and pruning of our neurons, connections-called synapses- and neuronal networks, through experience…we are cultivating our own neuronal networks.
—  Dr. James Zull, Biochem professor and author of  The Art of Changing the Brain – Enriching Teaching by Exploring the Biology of Learning.
How to measure the relevance of a voice you hear on the internet:

A series of thoughts you can implement to cope with criticism or hatred.

Step 1: if whatever this person is complaining about vanished, what would they do with themselves that is useful to society? Would they likely move on to complaining vehemently about something else? Or would they suddenly have time for their abandoned engineering careers, their medical degree, or perhaps their terrible art?

If the answer is “nothing”, then disregard them

Step 2: is this person actually trying to improve whatever situation it is they’re complaining about? Are they providing strategies, speaking in a way the welcomes equal and frank discussion, allows for ideas other than their own? Are they providing resources which a person can use to reproduce their opinions for themselves, or to assist in fixing the situation? Are citations being made? Is information being given in an even-handed way? If not, then they are not there to improve anything. They point out the discrepancies to mock them, not to heal them.

Step 3: Does the person honestly have a single ounce of care for the people with whom they clash? The best way to root out a professional duelist is to watch how easily he goes for his revolver - which is to say, attacking as a natural beginning is not constructive. It indicates a lack of care or concern for anyone but themselves. It means their opinion is entirely self-serving, and all other arguments they may make that incorporate other people or their situations (Using veterans to lambast a presidential administration for example) is only utilized as a pawn for their own selfish reasons. If no strategies, resources, alternatives are offered, and all arguments are framed in terms of abusive, dismissive language or exaggerated situations…they are there just to brawl…disregard.

Step 4: if the person uses nothing but inflammatory language, mockery, or sarcasm, they have but one thing in mind - which is to hurt the feelings of one group to entertain another. All their points are henceforth invalidated because they refused to obey the rules of decorum.

Step 5: if they tell you, in ANY capacity, that how you feel about something, how your soul reacts, is wrong…if they try to correct that with negative judgements or inflammatory language…they aren’t actually interested in your opinion. It contradicts theirs. They will not listen. They operate with the arrogance that allows them the freedom to question you, but not the humility to receive similar. They literally have a neuronal network weighted against your words and will never hear you. Don’t bother trying.

Step 6: if what they say makes you feel like ripping off one of their arms so that you can use the jagged bone to scoop out their eyes so that you can piss into their open skull…disregard them.

My advice in all cases is the same:

Leave it alone for a time. Walk away. Let your mind come up with all its clever rejoinders. Tell others. Vent your frustrations. Most importantly - breathe. Center yourself. Focus all that anger and hurt into a fine, thin sheet of steel, hammer and temper it in your focus, sharpen it on your energy level. But never wield it unless you’re willing to cross swords, fight for blood, be injured, divide your mind between the fray and the strategy.

Don’t tax yourself with responding to these people unless you know for a fact, you can outlast them. They have nothing else to live for. This is all there is for them. So their all goes into it.

If anything can compromise you or harm you…leave it.

Unless you know that someone else is being harmed, and then the decision is up to you. You can step in the way, deflect the rage, distract. Or you can walk away. Both have consequences.

But think on this: they’re relying on your strength to provide them with entertainment. They’re relying on weakness to let them keep shouting from their soapboxes. Either way you act, they are waiting for it and will get something from that if they can.

Because they are leeches. And as we have established in the steps of thought…have nothing constructive to add.

This goes for me too. I am old and set in my ways. I have certain notions about the world. I try to be flexible but I have my own thoughts. If I am ever all of these in one place with regards to an issue…

Please chastise me. I bite…but I will work hard not to.

Psychotherapy works by going deep into the brain and its neurons and changing their structure by turning on the right genes. Psychiatrist Dr. Susan Vaughan has argued that the talking cure works by ‘talking to neurons,’ and that an effective psychotherapist or psychoanalyst is a 'microsurgeon of the mind’ who helps patients make needed alterations in neuronal networks.
—  Norman Doidge, author of The Brain That Changes Itself
Scientists discover new mechanism of how brain networks form

Scientists have discovered that networks of inhibitory brain cells or neurons develop through a mechanism opposite to the one followed by excitatory networks. Excitatory neurons sculpt and refine maps of the external world throughout development and experience, while inhibitory neurons form maps that become broader with maturation. This discovery adds a new piece to the puzzle of how the brain organizes and processes information. Knowing how the normal brain works is an important step toward understanding the nature of neurological conditions and opens the possibility of finding treatments in the future. The results appear in Nature Neuroscience.

“The brain represents the external world as specific maps of activity created by networks of neurons,” said senior author Dr. Benjamin Arenkiel, associate professor of molecular and human genetics and of neuroscience at Baylor College of Medicine, who studies neural maps in the olfactory system of the laboratory mouse. “Most of these maps have been studied in the excitatory circuits of the brain because excitatory neurons in the cortex outnumber inhibitory neurons.”

The studies of excitatory maps have revealed that they begin as a diffuse and overlapping network of cells. “With time,” said Arenkiel, “experience sculpts this diffuse pattern of activity into better defined areas, such that individual mouse whiskers, for instance, are represented by discrete segments of the brain cortex. This progression from a diffuse to a refined pattern occurs in many areas of the brain.”

In addition to excitatory networks, the brain has inhibitory networks that also respond to external stimuli and regulate the activity of neural networks. How the inhibitory networks develop, however, has remained a mystery.

In this study, Arenkiel and colleagues studied the development of maps of inhibitory neurons in the olfactory system of the mouse.

Studying inhibitory brain networks of the mouse sense of smell

“Unlike sight, hearing or other senses, the sense of smell in the mouse detects discrete scents from a large array of molecules,” said Arenkiel, who is also a McNair Scholar at Baylor.

Mice can detect a vast number of scents thanks in part to a complex network of inhibitory neurons. Inhibitory neurons are the most abundant type of cells in the mouse brain area dedicated to process scent. To support this network, newly born inhibitory neurons are continually added and integrated into the circuits.

Arenkiel and colleagues followed the paths of these newly added neurons in time to determine how inhibitory circuits develop. First, they genetically labeled the cells so they would glow when the neurons were active. Then, they offered individual scents to the mice and visually recorded through a microscope the areas or networks of the brain that glowed for each scent the live, anesthetized animal smelled. The scientists repeated the experiment several times to determine how the networks changed as the animal learned to identify each scent.

Surprising result

The scientists expected that inhibitory networks would mature in a way similar to that of excitatory networks. That is, the more the animal experienced a scent, the better defined the networks of activity would become. Surprisingly, the scientists discovered that the inhibitory brain circuits of the mouse sense of smell develop in a manner opposite to the excitatory circuits. Instead of becoming narrowly defined areas, the inhibitory circuits become broader. Thanks to this new finding scientists now better understand how the brain organizes and processes information.

Arenkiel and colleagues think that the inhibitory networks work hand-in-hand with the excitatory networks. They propose that the interaction between excitatory and inhibitory networks could be compared to a network of roads (excitatory networks) whose traffic is regulated by a network of traffic lights (inhibitory networks). The scientists suggest that the formation of useful neural maps depends on inhibitory networks driving the refinement of excitatory networks, and that this new information will be essential towards developing new approaches for repairing brain tissue.

walkinredinstead challenge day two: #RedInstead

I didn’t want to post a selfie for this. It didn’t feel significant enough. My haircut, my eyes, the lines of my face, the shape of my nose, these are all the last things you need to know about me if you want to know autism. There is no autistic look, no physical trait, no outfit we all wear to be seen. Autism is our brain, the dense tissue of cells, fibers and liquid - the ugliest organ, one might say, a light shadow of pink and a lot of slime, nothing remarkable. Yet it holds all our thoughts and dreams, all our fears and hopes, all our memories, and our identities. All of the the things that make us, us.

Autism is our brain and it can’t be seen or heard or touched. But many things can be. Many things are so very obvious. My faked, exaggerated facial expressions and awkward raptor hands. My intonations, too high, too low, voice too loud, too expressive. My fingers, always moving, always going through rounds and rounds of repetitive motions. My shakes and flinches in reaction to bad sounds and unexpected touches. My words, often “smart” and sophisticated, sometimes carefully prepared, and repeated again and again. And my happy flappy hands when I feel the joy channel through me like a lighting strike. Those are things you can notice: if I allow you to. Or if I’m too tired to hide them.

I hide them because I have been taught to. Not by so-called therapists, thank god, but by people around me. They did not give me stickers for saying please and thank you. They did not take away my toys for not making eye contact. They just bullied and shamed me for years until I picked it up myself.

Every time a kid at school laughed at me for taking so long to tie my shoelaces, or ridiculed me for talking about science fiction, or tricked me into an embarrassing situation because they could - I learned. Every time a teacher blamed me for not being able to get up early in the morning, or accused me of deliberately being rude, or told my parents they should “beat me once or twice” to fix my problems - I remembered.

And I trained myself to pretend. I became an outstanding actor. I rehearsed every word, every expression, every step of every scenario, until I forgot why I was doing it. I painstakingly copied everyone I interacted with, from their smile to the way they moved their hands when talking, until I forgot what it was like to be myself. I thought I was broken, and I was repairing myself. Only it didn’t make me feel better. It only made me feel more broken.

I am autistic. It is in my brain, in that complicated network of neurons we call ourselves. But around me I have a shell. A cover, maybe, like the camouflage suits that solders wear. I made it for myself, one thread at a time, because I had to. Autism is there, underneath, but the outside world sees the cover. I know now I am not broken. I know now I am wired that way. I do not wish to have that cover anymore, yet I can’t get rid of it. I try to. I learn to live as an autistic person, not as a broken neurotypical, and I am shedding that cover, slowly, one thread at a time.

This is why we need acceptance, not awareness. Awareness would just put a new word in the mouth of my bullies to shout at my back. Awareness would just give a reason to my teachers not to help me and a cause to write down on my “expelled” papers. Awareness would just make me feel like I am a tragedy, a burden, a fate worse than death and… how is that any difference from what I felt for so many years?

Acceptance tells me that my struggles are real, and can be made less with support and accommodations. Acceptance tells me that the way I move, the way I talk, the way I am is okay, a part of natural human variation, and not something to be ashamed of. Acceptance tells me I am not alone, and there are people like me out there. Acceptance tells me my life can be beautiful, amazing, fulfilling, and just as happy as a neurotypical life, no matter how much help I need or how much I can do. Acceptance tells me - it is not all bad. There is a place in this world for you.

So today, do not support Autism Speaks, do not support Light It Up Blue, and do no support autism awareness. Awareness is the last thing we need right now! What we need is for people to understand us and to stop trying to fix us. Maybe we aren’t the ones who are broken. Maybe society is. Maybe it’s time to fix society. And then, there will be a place for us, just the way we are.

#AutismAcceptance
#RedInstead

Balancing Time and Space in the Brain: A New Model Holds Promise for Predicting Brain Dynamics

For as long as scientists have been listening in on the activity of the brain, they have been trying to understand the source of its noisy, apparently random, activity. In the past 20 years, “balanced network theory” has emerged to explain this apparent randomness through a balance of excitation and inhibition in recurrently coupled networks of neurons. A team of scientists has extended the balanced model to provide deep and testable predictions linking brain circuits to brain activity.

Lead investigators at the University of Pittsburgh say the new model accurately explains experimental findings about the highly variable responses of neurons in the brains of living animals. On Oct. 31, their paper, “The spatial structure of correlated neuronal variability,” was published online by the journal Nature Neuroscience.

The new model provides a much richer understanding of how activity is coordinated between neurons in neural circuits. The model could be used in the future to discover neural “signatures” that predict brain activity associated with learning or disease, say the investigators.

“Normally, brain activity appears highly random and variable most of the time, which looks like a weird way to compute,” said Brent Doiron, associate professor of mathematics at Pitt, senior author on the paper, and a member of the University of Pittsburgh Brain Institute (UPBI). “To understand the mechanics of neural computation, you need to know how the dynamics of a neuronal network depends on the network’s architecture, and this latest research brings us significantly closer to achieving this goal.”

Earlier versions of the balanced network theory captured how the timing and frequency of inputs—excitatory and inhibitory—shaped the emergence of variability in neural behavior, but these models used shortcuts that were biologically unrealistic, according to Doiron.

“The original balanced model ignored the spatial dependence of wiring in the brain, but it has long been known that neuron pairs that are near one another have a higher likelihood of connecting than pairs that are separated by larger distances. Earlier models produced unrealistic behavior—either completely random activity that was unlike the brain or completely synchronized neural behavior, such as you would see in a deep seizure. You could produce nothing in between.”

In the context of this balance, neurons are in a constant state of tension. According to co-author Matthew Smith, assistant professor of ophthalmology at Pitt and a member of UPBI, “It’s like balancing on one foot on your toes. If there are small overcorrections, the result is big fluctuations in neural firing, or communication.”

The new model accounts for temporal and spatial characteristics of neural networks and the correlations in the activity between neurons—whether firing in one neuron is correlated with firing in another. The model is such a substantial improvement that the scientists could use it to predict the behavior of living neurons examined in the area of the brain that processes the visual world.

After developing the model, the scientists examined data from the living visual cortex and found that their model accurately predicted the behavior of neurons based on how far apart they were. The activity of nearby neuron pairs was strongly correlated. At an intermediate distance, pairs of neurons were anticorrelated (When one responded more, the other responded less.), and at greater distances still they were independent.

“This model will help us to better understand how the brain computes information because it’s a big step forward in describing how network structure determines network variability,” said Doiron. “Any serious theory of brain computation must take into account the noise in the code. A shift in neuronal variability accompanies important cognitive functions, such as attention and learning, as well as being a signature of devastating pathologies like Parkinson’s disease and epilepsy.”

While the scientists examined the visual cortex, they believe their model could be used to predict activity in other parts of the brain, such as areas that process auditory or olfactory cues, for example. And they believe that the model generalizes to the brains of all mammals. In fact, the team found that a neural signature predicted by their model appeared in the visual cortex of living mice studied by another team of investigators.

“A hallmark of the computational approach that Doiron and Smith are taking is that its goal is to infer general principles of brain function that can be broadly applied to many scenarios. Remarkably, we still don’t have things like the laws of gravity for understanding the brain, but this is an important step for providing good theories in neuroscience that will allow us to make sense of the explosion of new experimental data that can now be collected,” said Nathan Urban, associate director of UPBI.

Researchers create organic nanowire synaptic transistors that emulate the working principles of biological synapses

A team of researchers with the Pohang University of Science and Technology in Korea has created organic nanowire synaptic transistors that emulate the working principles of biological synapses. As they describe in their paper published in the journal Science Advances, the artificial synapses they have created use much smaller amounts of power than other devices developed thus far and rival that of their biological counterparts.          

Scientists are taking multiple paths towards building next generation computers—some are fixated on finding a material to replace silicon, others are working towards building a quantum machine, while still others are busy trying to build something much more like the human mind. A hybrid system of sorts that has organic artificial parts meant to mimic those found in the brain. In this new effort, the team in Korea has reached a new milestone in creating an artificial synapse—one that has very nearly the same power requirements as those inside our skulls.

Up till now, artificial synapses have consumed far more power than human synapses, which researchers have calculated is on the order of 10 femtojoules each time a single one fires. The new synapse created by the team requires just 1.23 femtojoules per event—far lower than anything achieved thus far, and on par with their natural rival. Though it might seem the artificial creations are using less power, they do not perform the same functions just yet, so natural biology is still ahead. Plus there is the issue of transferring information from one neuron to another. The “wires” used by the human body are still much thinner than the metal kind still being used by scientists—still, researchers are gaining.

As part of this latest effort, the team placed 144 of their artificial synapses on a 4 inch wafer and connected them together in a two dimensional mesh with wires that were just 200 to 300 nanometers on average. The idea was to test the possibility of causing the synapses to fire (open or close) based on information coming from a wire, or being sent from other artificial neurons. Each synapse mimicked the natural kind in shape as well—they were long and thin and were made of two types of organic material that allowed for holding or releasing ions.

The new artificial synapses are one more step on the road towards a computer that works in ways very similar to the human brain, and most believe if we ever get there, the machines we create will be far more powerful than anything nature has ever produced.

Image: Schematic of biological neuronal network and an ONW ST that emulates a biological synapse.

Credit: Science Advances (2016)

Insect Nervous System Copied To Boost Computing Power

by Charles Q. Choi

Brains are the most powerful computers known. Now microchips built to mimic insects’ nervous systems have been shown to successfully tackle technical computing problems like object recognition and data mining, researchers say.

Attempts to recreate how the brain works are nothing new. Computing principles underlying how the organ operates have inspired computer programs known as neural networks, which have been used for decades to analyze data. The artificial neurons that make up these programs imitate the brain’s neurons, with each one capable of sending, receiving and processing information.

However, real biological neural networks rely on electrical impulses known as spikes. Simulating networks of spiking neurons with software is computationally intensive, setting limits on how long these simulations can run and how large they can get.

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🤓🐙🐶 #DidYouKnow octopuses have half a billion neurons throughout their bodies? This network of neurons make them about as smart as a dog! 🐙🦀 📽: Nature Video

Want to watch more OctoVideos?! Visit Instagram.com/Octonation and join the club 🐙😍❤️

Our minds consist of an intricate network of neurones more complex than the entire known universe itself. Our souls, a higher intangible existence within our perishable physical manifestation. The garden of possibilities unfathomable, infinite doors of knowledge beyond the grasp of time and it’s comprehension. And yet to think, we spend our entire lives ignorant of what is within us, happily distracted and amused by our frivolous desires.
When questioned by God (swt) upon our arrival; what have you achieved during the passage of your journey? What will be our answer.

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An image recognition network dreams about every object it knows. Part ½: animals

Video from Ville-Matias Heikkilä uses deep-dream like technique to reveal collected neural dataset on various animals (and not puppyslugs)- the video here displays 500 of them:

Network used: VGG CNN-S (pretrained with Imagenet)

There are 1000 output neurons in the network, one for each image recognition category. In this video, the output of each of these neurons is separately amplified using backpropagation (i.e. deep dreaming).

More Here

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Think back to a really vivid memory. Got it? Now try to remember what you had for lunch three weeks ago. That second memory probably isn’t as strong—but why not? Why do we remember some things, and not others? And why do memories eventually fade?

Let’s look at how memories form in the first place. When you experience something – like dialing a phone number – the experience is converted into a pulse of electrical energy that zips along a network of neurons. Information first lands in short term memory where it’s available for anywhere from a few seconds to a couple of minutes. It’s then transferred to long-term memory through areas such as the hippocampus and finally to several storage regions  across the brain. Neurons throughout the brain communicate at dedicated sites called synapses using specialized neurotransmitters. If two neurons communicate repeatedly a remarkable thing happens – the efficiency of communication between them increases. This process, called long-term potentiation, is considered to be a mechanism by which memories are stored long-term.

But why do memories fade? Check out the TED-Ed Lesson How memories form and how we lose them - Catharine Young

Animation by Patrick Smith

Can the brain feel it? The world’s smallest extracellular needle-electrodes

A research team in the Department of Electrical and Electronic Information Engineering and the Electronics-Inspired Interdisciplinary Research Institute (EIIRIS) at Toyohashi University of Technology developed 5-μm-diameter needle-electrodes on 1 mm × 1 mm block modules. This tiny needle may help solve the mysteries of the brain and facilitate the development of a brain-machine interface. The research results were reported in Scientific Reports
on Oct 25, 2016.

(Image caption: Extracellular needle-electrode with a diameter of 5 μm mounted on a connector)

The neuron networks in the human brain are extremely complex. Microfabricated silicon needle-electrode devices were expected to be an innovation that would be able to record and analyze the electrical activities of the microscale neuronal circuits in the brain.

However, smaller needle technologies (e.g., needle diameter < 10 μm) are necessary to reduce damage to brain tissue. In addition to the needle geometry, the device substrate should be minimized not only to reduce the total amount of damage to tissue but also to enhance the accessibility of the
electrode in the brain. Thus, these electrode technologies will realize new experimental neurophysiological concepts.

A research team in the Department of Electrical and Electronic Information Engineering and the EIIRIS at Toyohashi University of Technology developed 5-
μm-diameter needle-electrodes on 1 mm × 1 mm block modules.

The individual microneedles are fabricated on the block modules, which are small enough to use in the narrow spaces present in brain tissue; as demonstrated in the recording using mouse cerebrum cortices. In addition, the block module remarkably improves the design variability in the packaging, offering numerous in vivo recording applications.

“We demonstrated the high design variability in the packaging of our electrode device, and in vivo neuronal recordings were performed by simply placing the device on a mouse’s brain. We were very surprised that high quality signals of a single unit were stably recorded over a long period using the 5-μm-diameter needle,” explained the first author, Assistant Professor Hirohito Sawahata, and co-author, researcher Shota Yamagiwa.

The leader of the research team, Associate Professor Takeshi Kawano said: “Our silicon needle technology offers low invasive neuronal recordings and provides novel methodologies for electrophysiology; therefore, it has the potential to enhance experimental neuroscience.” He added, “We expect the development of applications to solve the mysteries of the brain and the development of brain–machine interfaces.”

Supporting the damaged brain

A new study shows that embryonic nerve cells can functionally integrate into local neural networks when transplanted into damaged areas of the visual cortex of adult mice.

(Image caption: Neuronal transplants (blue) connect with host neurons (yellow) in the adult mouse brain in a highly specific manner, rebuilding neural networks lost upon injury. Credit: Sofia Grade, LMU/Helmholtz Zentrum München)

When it comes to recovering from insult, the adult human brain has very little ability to compensate for nerve-cell loss. Biomedical researchers and clinicians are therefore exploring the possibility of using transplanted nerve cells to replace neurons that have been irreparably damaged as a result of trauma or disease. Previous studies have suggested there is potential to remedy at least some of the clinical symptoms resulting from acquired brain disease through the transplantation of fetal nerve cells into damaged neuronal networks. However, it is not clear whether transplanted intact neurons can be sufficiently integrated to result in restored function of the lesioned network. Now researchers based at LMU Munich, the Max Planck Institute for Neurobiology in Martinsried and the Helmholtz Zentrum München have demonstrated that, in mice, transplanted embryonic nerve cells can indeed be incorporated into an existing network in such a way that they correctly carry out the tasks performed by the damaged cells originally found in that position. Such work is of importance in the potential treatment of all acquired brain disease including neurodegenerative illnesses such as Alzheimer‘s or Parkinson’s disease, as well as strokes and trauma, given each disease state leads to the large-scale, irreversible loss of nerve cells and the acquisition of a what is usually a lifelong neurological deficit for the affected person.

In the study published in Nature, researchers of the Ludwig Maximilians University Munich, the Max Planck Institute of Neurobiology, and the Helmholtz Zentrum München have specifically asked whether transplanted embryonic nerve cells can functionally integrate into the visual cortex of adult mice. “This region of the brain is ideal for such experiments,” says Magdalena Götz, joint leader of the study together with Mark Hübener. Hübener is a specialist in the structure and function of the mouse visual cortex in Professor Tobias Bonhoeffer’s Department (Synapses – Circuits – Plasticity) at the MPI for Neurobiology. As Hübener explains, “we know so much about the functions of the nerve cells in this region and the connections between them that we can readily assess whether the implanted nerve cells actually perform the tasks normally carried out by the network.” In their experiments, the team transplanted embryonic nerve cells from the cerebral cortex into lesioned areas of the visual cortex of adult mice. Over the course of the following weeks and months, they monitored the behavior of the implanted, immature neurons by means of two-photon microscopy to ascertain whether they differentiated into so-called pyramidal cells, a cell type normally found in the area of interest. “The very fact that the cells survived and continued to develop was very encouraging,” Hübener remarks. “But things got really exciting when we took a closer look at the electrical activity of the transplanted cells.” In their joint study, PhD student Susanne Falkner and Postdoc Sofia Grade were able to show that the new cells formed the synaptic connections that neurons in their position in the network would normally make, and that they responded to visual stimuli.

The team then went on to characterize, for the first time, the broader pattern of connections made by the transplanted neurons. Astonishingly, they found that pyramidal cells derived from the transplanted immature neurons formed functional connections with the appropriate nerve cells all over the brain. In other words, they received precisely the same inputs as their predecessors in the network. In addition, they were able to process that information and pass it on to the downstream neurons which had also differentiated in the correct manner. “These findings demonstrate that the implanted nerve cells have integrated with high precision into a neuronal network into which, under normal conditions, new nerve cells would never have been incorporated,” explains Götz, whose work at the Helmholtz Zentrum and at LMU focuses on finding ways to replace lost neurons in the central nervous system. The new study reveals that immature neurons are capable of correctly responding to differentiation signals in the adult mammalian brain and can close functional gaps in an existing neural network.

How Traumatic Memories Hide In The Brain, And How To Retrieve Them

Some stressful experiences – such as chronic childhood abuse – are so overwhelming and traumatic, the memories hide like a shadow in the brain.

At first, hidden memories that can’t be consciously accessed may protect the individual from the emotional pain of recalling the event. But eventually those suppressed memories can cause debilitating psychological problems, such as anxiety, depression, post-traumatic stress disorder or dissociative disorders.

A process known as state-dependent learning is believed to contribute to the formation of memories that are inaccessible to normal consciousness. Thus, memories formed in a particular mood, arousal or drug-induced state can best be retrieved when the brain is back in that state.

In a new study with mice, Northwestern Medicine scientists have discovered for the first time the mechanism by which state-dependent learning renders stressful fear-related memories consciously inaccessible.

“The findings show there are multiple pathways to storage of fear-inducing memories, and we identified an important one for fear-related memories,” said principal investigator Dr. Jelena Radulovic, the Dunbar Professor in Bipolar Disease at Northwestern University Feinberg School of Medicine. “This could eventually lead to new treatments for patients with psychiatric disorders for whom conscious access to their traumatic memories is needed if they are to recover.”

It’s difficult for therapists to help these patients, Radulovic said, because the patients themselves can’t remember their traumatic experiences that are the root cause of their symptoms.

The best way to access the memories in this system is to return the brain to the same state of consciousness as when the memory was encoded, the study showed.

The study was published August 17 in Nature Neuroscience.

Changing the Brain’s Radio Frequencies

Two amino acids, glutamate and GABA, are the yin and yang of the brain, directing its emotional tides and controlling whether nerve cells are excited or inhibited (calm). Under normal conditions the system is balanced. But when we are hyper-aroused and vigilant, glutamate surges. Glutamate is also the primary chemical that helps store memories in our neuronal networks in a way that they are easy to remember.

GABA, on the other hand, calms us and helps us sleep, blocking the action of the excitable glutamate. The most commonly used tranquilizing drug, benzodiazepine, activates GABA receptors in our brains.

There are two kinds of GABA receptors. One kind, synaptic GABA receptors, works in tandem with glutamate receptors to balance the excitation of the brain in response to external events such as stress.

The other population, extra-synaptic GABA receptors, are independent agents. They ignore the peppy glutamate. Instead, their job is internally focused, adjusting brain waves and mental states according to the levels of internal chemicals, such as GABA, sex hormones and micro RNAs. Extra-synaptic GABA receptors change the brain’s state to make us aroused, sleepy, alert, sedated, inebriated or even psychotic. However, Northwestern scientists discovered another critical role; these receptors also help encode memories of a fear-inducing event and then store them away, hidden from consciousness.

“The brain functions in different states, much like a radio operates at AM and FM frequency bands,” Radulovic said. “It’s as if the brain is normally tuned to FM stations to access memories, but needs to be tuned to AM stations to access subconscious memories. If a traumatic event occurs when these extra-synaptic GABA receptors are activated, the memory of this event cannot be accessed unless these receptors are activated once again, essentially tuning the brain into the AM stations.”

Retrieving Stressful Memories in Mice

In the experiment, scientists infused the hippocampus of mice with gaboxadol, a drug that stimulates extra-synaptic GABA receptors. “It’s like we got them a little inebriated, just enough to change their brain state,” Radulovic said.

Then the mice were put in a box and given a brief, mild electric shock. When the mice were returned to the same box the next day, they moved about freely and weren’t afraid, indicating they didn’t recall the earlier shock in the space. However, when scientists put the mice back on the drug and returned them to the box, they froze, fearfully anticipating another shock.

“This establishes when the mice were returned to the same brain state created by the drug, they remembered the stressful experience of the shock,” Radulovic said.

The experiment showed when the extra-synaptic GABA receptors were activated with the drug, they changed the way the stressful event was encoded. In the drug-induced state, the brain used completely different molecular pathways and neuronal circuits to store the memory.

“It’s an entirely different system even at the genetic and molecular level than the one that encodes normal memories,” said lead study author Vladimir Jovasevic, who worked on the study when he was a postdoctoral fellow in Radulovic’s lab.

This different system is regulated by a small microRNA, miR-33, and may be the brain’s protective mechanism when an experience is overwhelmingly stressful.

The findings imply that in response to traumatic stress, some individuals, instead of activating the glutamate system to store memories, activate the extra-synaptic GABA system and form inaccessible traumatic memories.

Traumatic Memories Rerouted and Hidden Away

Memories are usually stored in distributed brain networks including the cortex, and can thus be readily accessed to consciously remember an event. But when the mice were in a different brain state induced by gaboxadol, the stressful event primarily activated subcortical memory regions of the brain. The drug rerouted the processing of stress-related memories within the brain circuits so that they couldn’t be consciously accessed.