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