Masked Fears: Are Fears That Are Seemingly Overcome Only Hidden?

Masked Fears: Are Fears That Are Seemingly Overcome Only Hidden?

  8:34:00 AM    Science Lover

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Fear is a natural part of our emotional life and acts as a necessary protection mechanism. However, fears sometimes grow beyond proportions and become difficult to shed. Scientists from Freiburg, Basel and Bordeaux have used computer simulations to understand the processes within the brain during the formation and extinction of fears.

One group of nerve cells in the brain controls the fear 
behaviour (right). This can be suppressed by a second 
group of nerve cells (left) -- but the fear is only masked, 
and has not disappeared completely. (Credit: Carlos 
Toledo/Bernstein Center Freiburg)

In the current issue of the scientific journal PLoS Computational Biology, Ioannis Vlachos from the Bernstein Center Freiburg and colleagues propose for the first time an explanation for how fears that were seemingly overcome are in reality only hidden.

The reason for the persistency of fears is that, literally, their roots run deep: Far below the cerebral cortex lies the "amygdala," which plays a crucial role in fear processes. Fear is commonly investigated in mice by exposing them simultaneously to a neutral stimulus -- a certain sound, for example -- and an unpleasant one. This leads to the animals being frightened of the sound as well. Context plays an important role in this case: If the scaring sound is played repeatedly in a new context without anything bad happening, the mice shed their fear again. It returns immediately, however, if the sound is presented in the original, or even a completely novel context. Had the mice not unlearned to be frightened after all?

The fact that fears can be "masked" has been known for some time. Recently, two co-authors of the present study discovered that two groups of nerve cells within the amygdala are involved in this process. By creating a model of the amygdala's neuronal network, Ioannis Vlachos and colleagues were now able to find an explanation for how such a masking of fears is implemented in the brain: One group of cells is responsible for the fear response, the second for its suppression. Activity of the latter inhibits the former and, thus, prevents fear signals to be transmitted to other parts of the brain. Nevertheless, the change in their connections that resulted in an increased activity in the fear-coding neurons in the first place, is still present. As soon as the masking by the fear-suppressing neurons disappears, for example by changing the context, these connections come into action again -- the fear returns.

According to the scientists, these insights can be transferred to us humans, helping to treat fears more successfully in the future.

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Brainy Worms: Scientists Uncover Counterpart of Cerebral Cortex in Marine Worms

Brainy Worms: Scientists Uncover Counterpart of Cerebral Cortex in Marine Worms

  11:20:00 AM    Science Lover

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Our cerebral cortex, or pallium, is a big part of what makes us human: art, literature and science would not exist had this most fascinating part of our brain not emerged in some less intelligent ancestor in prehistoric times. But when did this occur and what were these ancestors? Unexpectedly, scientists at the European Molecular Biology Laboratory (EMBL) in Heidelberg, Germany, have now discovered a true counterpart of the cerebral cortex in an invertebrate, a marine worm.

A virtual Platynereis brain (left), created by averaging microscopy images of the brains of 36 different individuals, onto which scientists mapped gene activity (right). Perspective shows the brain as viewed from inside a Platynereis larvae, at 48 hours' old. (Credit: EMBL/R.Tomer)

Their findings are published in Cell, and give an idea of what the most ancient higher brain centres looked like, and what our distant ancestors used them for.

It has long been clear that, in evolutionary terms, we share our pallium with other vertebrates, but beyond that was mystery. This is because even invertebrates that are clearly related to us -- such as the fish-like amphioxus -- appear to have no similar brain structures, nothing that points to a shared evolutionary past. But EMBL scientists have now found brain structures related to the vertebrate pallium in a very distant cousin -- the marine ragworm Platynereis dumerilii, a relative of the earthworm -- which last shared an ancestor with us around 600 million years ago.

"Two stunning conclusions emerge from this finding," explains Detlev Arendt, who headed the study: "First, the pallium is much older than anyone would have assumed, probably as old as higher animals themselves. Second, we learn that it came out of 'the blue' -- as an adaptation to early marine life in Precambrian oceans."

To uncover the evolutionary origins of our brain, EMBL scientist Raju Tomer, who designed and conducted the work, took an unprecedentedly deep look at the regions of Platynereis dumerilii's brain responsible for processing olfactory information -- the mushroom-bodies. He developed a new technique, called cellular profiling by image registration (PrImR), which is the first to enable scientists to investigate a large number of genes in a compact brain and determine which are turned on simultaneously. This technique enabled Tomer to determine each cell's molecular fingerprint, defining cell types according to the genes they express, rather than just based on their shape and location as was done before.

"Comparing the molecular fingerprints of the developing ragworms' mushroom-bodies to existing information on the vertebrate pallium," Arendt says, " it became clear that they are too similar to be of independent origin and must share a common evolutionary precursor."

This ancestral structure was likely a group of densely packed cells, which received and processed information about smell and directly controlled locomotion. It may have enabled our ancestors crawling over the sea floor to identify food sources, move towards them, and integrate previous experiences into some sort of learning.

"Most people thought that invertebrate mushroom-bodies and vertebrate pallium had arisen independently during the course of evolution, but we have proven this was most probably not the case," says Tomer. Arendt concludes: "The evolutionary history of our cerebral cortex has to be rewritten."

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Computer Model: Neurons Coordinate Messages

Computer Model: Neurons Coordinate Messages

  2:45:00 PM    Science Lover

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There is strength in numbers if you want to get your voice heard. But how to do you get your say if you are in the minority? That's a dilemma faced not only by the citizens of a democracy but also by some neurons in the brain.

Although they only account for a fraction of the synapses in the visual cortex, neurons in the thalamus get their message across loud and clear by coordination -- simultaneously hitting the "send" button -- according to a computer simulation developed by researchers at the Salk Institute for Biological Studies.

This is an image of a spiny stellate cell. 
(Credit: This image originally appeared in 
Churchill et al. BMC Neuroscience 2004 5:43.)

Their findings, published in the April 2, 2010 issue of the journal Science, hold important clues to how the brain encodes and processes information, which can be applied to a wide variety of applications, from understanding psychiatric disorders to the development of novel pharmaceuticals and new ways of handling information by computers or communication networks.

Historically, neuroscientists have been limited to recording the activity of single brain cells, which led to the widely accepted view that neurons communicate with each other through volleys of electrical spikes and that they increase the average rate of spiking to "speak up."

But communication between neurons is not limited to one-on-one interactions. Instead, any given cell receives signals from hundreds of cells, which send their messages through thousands of synapses, specialized junctions that allow signals to pass from one neuron to the next.

"Unfortunately, we don't have the technology yet to actually measure what all these neurons are saying to the recipient cell, which would require recording simultaneously from hundreds of cells, " says graduate student and first author Hsi-Ping Wang. "For this reason, nobody could answer a very basic question that's been puzzling neuroscientist for decades, which is: 'How many neurons or synapses does it take to reliably send a signal from point A to point B?'"

This question is particularly pressing for the thalamus, the central switchboard that processes and distributes incoming sensory information to all parts of the cortex. Thalamic input only accounts for five percent of the signals that so-called spiny stellate cells in the cortex receive, even though they drive a good portion of activity throughout the cerebral cortex.

"That is a paradox," says Howard Hughes Medical Institute investigator Terrence J. Sejnowski, Ph.D., professor and head of the Computational Neurobiology Laboratory. "How can so few synapses have such a big impact? If the average spiking rate were the determining factor, thalamic input would be drowned out by the other 95 percent of the inputs from other cortical cells."

Based on the assumption that the brain cares about the reliability and precision of spikes, Sejnowki's team developed a realistic computer model of a spiny stellate cell and the signals it receives through its roughly 6,000 synapses. "We found that it is not the number of spikes that's relevant but rather how many spikes arrive at the same time," says Sejnowski.

"Surprisingly, our model predicts that it only takes about 30 synapses out of 6,000 firing simultaneously to create extremely reliable signaling," explains Wang, "and our prediction lines up with currently available in vivo measurements and understanding. You could have all 6,000 synapses firing at the same time, but it would be a waste of resources."

The researchers hope that their findings will give them new insight into the holy grail of neurobiology: decoding the neural code or language of the brain. If the eye receives the same visual information under identical conditions over and over again, one would expect that the signal, the series of generated spikes or bits, is essentially the same.

"But it's not known whether that happens under natural conditions, and it's technically very difficult to measure, " says senior researcher and co-author Donald Spencer, Ph.D. "That's where the power of computational neurobiology really comes to bear on otherwise intractable questions."

"Applying theories of engineering to the study of the brain has helped us gain new insight into how neurons communicate with each other," says Wang. "On the other hand, there are certain things that the brain does in unique ways that are completely different from how computers work. A better understanding of the brain allows us the capture these algorithms and could very well affect the things engineers do in everyday life."

Jean-Marc Fellous, an associate professor in the Department of Psychology and Applied Mathematics at the University of Arizona, also contributed to the work.

The work was supported by the Howard Hughes Medical Institute.

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