Animal study highlights potential new target for treating anxiety disorders
Increasing acidity in the brain’s emotional control center reduces anxiety, according to an animal study published February 26 in The Journal of Neuroscience. The findings suggest a new mechanism for the body’s control of fear and anxiety, and point to a new target for the treatment of anxiety disorders.
Anxiety disorders, which are characterized by an inability to control feelings of fear and uncertainty, are the most prevalent group of psychiatric diseases. At the cellular level, these disorders are associated with heightened activity in the basolateral amygdala (BLA), which is known to play a central role in emotional behavior.
Many cells in the BLA possess acid-sensing ion channels called ASIC1a, which respond to pH changes in the environment outside of the cell. Maria Braga, DDS, PhD, and colleagues at the Uniformed Services University of the Health Sciences, F. Edward Hébert School of Medicine, found that activating ASIC1a decreased the activity of nearby cells and reduced anxiety-like behavior in animals. These findings add to previous evidence implicating the role of ASIC1a in anxiety.
“These findings suggest that activating these channels, specifically in fear-related areas such as the amygdala, may be a key to regulating anxiety,” explained Anantha Shekhar, MD, PhD, who studies panic disorders at Indiana University and was not involved in this study. “Developing specific drugs that can stimulate these channels could provide a new way to treat anxiety and fear disorders such a post-traumatic stress and panic disorders.”
To determine the effect ASIC1a activation has on neighboring cells, Braga’s group bathed BLA cells in an acidic solution in the laboratory and measured the signals sent to nearby cells. Lowering the pH of the solution decreased the activity of cells in the BLA.
Activating ASIC1a also affected animal behavior. When the researchers administered a drug that blocks ASIC1a directly into the BLA of rats, the rats displayed more anxiety-like behavior than animals that did not receive the drug. In contrast, when rats received a drug designed to increase the activity of ASIC1a channels in the BLA, the animals displayed less anxiety-like behavior.
“Our study emphasizes the importance of identifying and elucidating mechanisms involved in the regulation of brain function for the development of more efficacious therapies for treating psychiatric and neurological illnesses,” Braga said. While the findings suggest that drugs targeting ASICs may one day lead to novel therapies for anxiety disorders, Braga noted that “more research is needed to understand the roles that ASIC1a channels play in the brain.”
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Swedish researchers at Uppsala University have, together with Brazilian collaborators, discovered a new group of nerve cells that regulate processes of learning and memory. These cells act as gatekeepers and carry a receptor for nicotine, which can help explain our ability to remember and sort information.
The discovery of the gatekeeper cells, which are part of a memory network together with several other nerve cells in the hippocampus, reveal new fundamental knowledge about learning and memory. The study is published today in Nature Neuroscience.
The hippocampus is an area of the brain that is important for consolidation of information into memories and helps us to learn new things. The newly discovered gatekeeper nerve cells, also called OLM-alpha2 cells, provide an explanation to how the flow of information is controlled in the hippocampus. Read more…
Taking a trip down memory lane while you are driving could land you in a roadside ditch, new research indicates.
Vanderbilt University psychologists have found that our visual perception can be contaminated by memories of what we have recently seen, impairing our ability to properly understand and act on what we are currently seeing.
“This study shows that holding the memory of a visual event in our mind for a short period of time can ‘contaminate’ visual perception during the time that we’re remembering,” Randolph Blake, study co-author and Centennial Professor of Psychology, said.
“Our study represents the first conclusive evidence for such contamination, and the results strongly suggest that remembering and perceiving engage at least some of the same brain areas.” Read more…
A new method facilitates the mapping of connections between neurons.
The human brain accomplishes its remarkable feats through the interplay of an unimaginable number of neurons that are interconnected in complex networks. A team of scientists from the Max Planck Institute for Dynamics and Self-Organization, the University of Göttingen and the Bernstein Center for Computational Neuroscience Göttingen has now developed a method for decoding neural circuit diagrams. Using measurements of total neuronal activity, they can determine the probability that two neurons are connected with each other.
The human brain consists of around 80 billion neurons, none of which lives or functions in isolation. The neurons form a tight-knit network that they use to exchange signals with each other. The arrangement of the connections between the neurons is far from arbitrary, and understanding which neurons connect with each other promises to provide valuable information about how the brain works. At this point, identifying the connection network directly from the tissue structure is practically impossible, even in cell cultures with only a few thousand neurons. In contrast, there are currently well-developed methods for recording dynamic neuronal activity patterns. Such patterns indicate which neuron transmitted a signal at what time, making them a kind of neuronal conversation log. The Göttingen-based team headed by Theo Geisel, Director at the Max Planck Institute for Dynamics and Self-Organization, has now made use of these activity patterns. Read more…
The Who asked “who are you?” but Dartmouth neurobiologist Jeffrey Taube asks “where are you?” and “where are you going?” Taube is not asking philosophical or theological questions. Rather, he is investigating nerve cells in the brain that function in establishing one’s location and direction.
Taube, a professor in the Department of Psychological and Brain Sciences, is using microelectrodes to record the activity of cells in a rat’s brain that make possible spatial navigation—how the rat gets from one place to another—from “here” to “there.” But before embarking to go “there,” you must first define “here.”
“Knowing what direction you are facing, where you are, and how to navigate are really fundamental to your survival,” says Taube. “For any animal that is preyed upon, you’d better know where your hole in the ground is and how you are going to get there quickly. And you also need to know direction and location to find food resources, water resources, and the like.”
Not only is this information fundamental to your survival, but knowing your spatial orientation at a given moment is important in other ways, as well. Taube points out that it is a sense or skill that you tend to take for granted, which you subconsciously keep track of. “It only comes to your attention when something goes wrong, like when you look for your car at the end of the day and you can’t find it in the parking lot,” says Taube. Read more…
Our interpretation of the world around us may have more in common with the impossible staircase illusion than it does the real world, according to research published today in the open access journal PLoS ONE.
A ‘Penrose stairs’ optical illusion, or impossible staircase. Image adapted from public domain image shared by Sakurambo on Wikimedia
The study, which was funded by the Wellcome Trust, suggests that we do not hold a three-dimensional representation of our surroundings in our heads as was previously thought.
Artists, such as Escher, have often exploited the paradoxes that emerge when a 3D scene is depicted by means of a flat, two-dimensional picture. In Escher’s famous picture ‘Waterfall’, for example, it is impossible to tell whether the start of the waterfall is above or below its base.
Paradoxes like this can be generated in a drawing, but it is not possible to create such a 3D structure. The illusion is possible because drawings of 3D scenes are inherently ambiguous, so there is no one-to-one relationship between the picture and 3D locations in space.
Most theories of 3D vision and how we represent space in our visual system assume that we generate a one-to-one 3D model of space in our brains, where each point in real space maps to a unique point in our model. However, there is an ongoing debate about whether this is really the case.
To test this idea, researchers at the University of Reading placed participants wearing a virtual reality headset in a virtual room in which they had to judge which of two objects was the nearest. On some occasions, the size of the room was increased four-fold – previous research by the team showed that participants fail to notice this expansion.
In this new study, the researchers found that people’s judgement of the relative depth of objects depended on the order in which the objects were compared. Although the results are readily explained in relation to the expansion of the room, the participants had no idea that the room changed at any stage during the experiment. It is the properties of this stable perception that the experiment tested.
Dr Andrew Glennerster from the University of Reading, who led the study, explains: “In the impossible staircase illusion, you cannot tell whether the back corner is higher or lower than the front one as it depends which route you take to get there. The same is true, we find, in our task. This means that our own internal representations of space must be rather like Escher’s paradoxes, with no one-to-one relationship to real space.”
“Even when the size of the room increases four-fold, people think they are in a stable room throughout the experiment. Their interpretation of the room does not update itself when the room itself changes.
“Does it make sense for their representation of the room to have 3D coordinates, as a proper staircase would? No – there is no way to write down the coordinates of the objects that could explain the judgements people made. Visual space – the internal representation – is much more like the paradoxical staircase than a physically realisable model.”
Wellcome Trust press release
Image Source: NeuroscienceNews.com image adapted from public domain image with credit to Sakurambo on Wikipedia.
Original Research: Research article “A demonstration of ‘broken’ visual space” by Svarverud E et al. to appear in PLoS ONE 2012
Scripps Research Institute Team Wrests Partial Control of a Memory
The work advances understanding of how memories form and offers new insight into disorders such as schizophrenia and post traumatic stress disorder.
Scripps Research Institute scientists and their colleagues have successfully harnessed neurons in mouse brains, allowing them to at least partially control a specific memory. Though just an initial step, the researchers hope such work will eventually lead to better understanding of how memories form in the brain, and possibly even to ways to weaken harmful thoughts for those with conditions such as schizophrenia and post traumatic stress disorder.
The results are reported in the March 23, 2012 issue of the journal Science.
Researchers have known for decades that stimulating various regions of the brain can trigger behaviors and even memories. But understanding the way these brain functions develop and occur normally—effectively how we become who we are—has been a much more complex goal.
“The question we’re ultimately interested in is: How does the activity of the brain represent the world?” said Scripps Research neuroscientist Mark Mayford, who led the new study. “Understanding all this will help us understand what goes wrong in situations where you have inappropriate perceptions. It can also tell us where the brain changes with learning.”
On-Off Switches and a Hybrid Memory
As a first step toward that end, the team set out to manipulate specific memories by inserting two genes into mice. One gene produces receptors that researchers can chemically trigger to activate a neuron. They tied this gene to a natural gene that turns on only in active neurons, such as those involved in a particular memory as it forms, or as the memory is recalled. In other words, this technique allows the researchers to install on-off switches on only the neurons involved in the formation of specific memories.
For the study’s main experiment, the team triggered the “on” switch in neurons active as mice were learning about a new environment, Box A, with distinct colors, smells and textures.
Next the team placed the mice in a second distinct environment—Box B—after giving them the chemical that would turn on the neurons associated with the memory for Box A. The researchers found the mice behaved as if they were forming a sort of hybrid memory that was part Box A and part Box B. The chemical switch needed to be turned on while the mice were in Box B for them to demonstrate signs of recognition. Alone neither being in Box B nor the chemical switch was effective in producing memory recall.
“We know from studies in both animals and humans that memories are not formed in isolation but are built up over years incorporating previously learned information,” Mayford said. “This study suggests that one way the brain performs this feat is to use the activity pattern of nerve cells from old memories and merge this with the activity produced during a new learning session.”
Future Manipulation of the Past
The team is now making progress toward more precise control that will allow the scientists to turn one memory on and off at will so effectively that a mouse will in fact perceive itself to be in Box A when it’s in Box B.
Once the processes are better understood, Mayford has ideas about how researchers might eventually target the perception process through drug treatment to deal with certain mental diseases such as schizophrenia and post traumatic stress disorder. With such problems, patients’ brains are producing false perceptions or disabling fears. But drug treatments might target the neurons involved when a patient thinks about such fear, to turn off the neurons involved and interfere with the disruptive thought patterns.
Notes about this memory research article
In addition to Mayford, other authors of the paper, “Generation of a Synthetic Memory Trace,” are Aleena Garner, Sang Youl Hwang, and Karsten Baumgaertel from Scripps Research, David Rowland and Cliff Kentros from the University of Oregon, Eugene, and Bryan Roth from the University of North Carolina (UNC), Chapel Hill.
This work is supported by the National Institute of Mental Health, the National Institute on Drug Abuse, the California Institute for Regenerative Medicine, and the Michael Hooker Distinguished Chair in Pharmacology at UNC.
Original Research: Abstract for “Generation of a Synthetic Memory Trace” by Aleena R. Garner, David C. Rowland, Sang Youl Hwang, Karsten Baumgaertel, Bryan L. Roth, Cliff Kentros & Mark Mayford in Science