Posts tagged neural circuit
Articles and news from the latest research reports.
Single-Neuron “Hub” Orchestrates Activity of an Entire Brain Circuit
The idea of mapping the brain is not new. Researchers have known for years that the key to treating, curing, and even preventing brain disorders such as Alzheimer’s disease, epilepsy, and traumatic brain injury, is to understand how the brain records, processes, stores, and retrieves information.
New Tel Aviv University research published in PLOS Computational Biology makes a major contribution to efforts to navigate the brain. The study, by Prof. Eshel Ben-Jacob and Dr. Paolo Bonifazi of TAU’s School of Physics and Astronomy and Sagol School of Neuroscience, and Prof. Alessandro Torcini and Dr. Stefano Luccioli of the Instituto dei Sistemi Complessi, under the auspices of TAU’s Joint Italian-Israeli Laboratory on Integrative Network Neuroscience, offers a precise model of the organization of developing neuronal circuits.
In an earlier study of the hippocampi of newborn mice, Dr. Bonifazi discovered that a few “hub neurons” orchestrated the behavior of entire circuits. In the new study, the researchers harnessed cutting-edge technology to reproduce these findings in a computer-simulated model of neuronal circuits. “If we are able to identify the cellular type of hub neurons, we could try to reproduce them in vitro out of stem cells and transplant these into aged or damaged brain circuitries in order to recover functionality,” said Dr. Bonifazi.
Flight dynamics and brain neurons
"Imagine that only a few airports in the world are responsible for all flight dynamics on the planet," said Dr. Bonifazi. "We found this to be true of hub neurons in their orchestration of circuits’ synchronizations during development. We have reproduced these findings in a new computer model."
According to this model, one stimulated hub neuron impacts an entire circuit dynamic; similarly, just one muted neuron suppresses all coordinated activity of the circuit. “We are contributing to efforts to identify which neurons are more important to specific neuronal circuits,” said Dr. Bonifazi. “If we can identify which cells play a major role in controlling circuit dynamics, we know how to communicate with an entire circuit, as in the case of the communication between the brain and prosthetic devices.”
Conducting the orchestra of the brain
In the course of their research, the team found that the timely activation of cells is fundamental for the proper operation of hub neurons, which, in turn, orchestrate the entire network dynamic. In other words, a clique of hubs works in a kind of temporally-organized fashion, according to which “everyone has to be active at the right time,” according to Dr. Bonifazi.
Coordinated activation impacts the entire network. Just by alternating the timing of the activity of one neuron, researchers were able to affect the operation of a small clique of neurons, and finally that of the entire network.
"Our study fits within framework of the ‘complex network theory,’ an emerging discipline that explores similar trends and properties among all kinds of networks — i.e., social networks, biological networks, even power plants," said Dr. Bonifazi. "This theoretical approach offers key insights into many systems, including the neuronal circuit network in our brains."
Parallel to their theoretical study, the researchers are conducting experiments on in vitro cultured systems to better identify electrophysiological and chemical properties of hub neurons. The joint Italy-Israel laboratory is also involved in a European project aimed at linking biological and artificial neuronal circuitries to restore lost brain functions.
(Source: aftau.org)
Variations in Neuronal Networks Could Explain Traumatic Brain Injury Outcomes
A team of researchers at the Neuroscience Institute at Georgia State University has discovered that hidden differences in the properties of neural circuits can account for whether animals are behaviorally susceptible to brain injury. These results could have implications for the treatment of brain trauma.
People vary in their responses to stroke and trauma, which impedes the ability of physicians to predict patient outcomes. Damage to the brain and nervous system can lead to severe disabilities, including epilepsy and cognitive impairment.
If doctors could predict outcomes with greater accuracy, patients might benefit from more tailored treatments. Unfortunately, the complexity of the human brain hinders efforts to explain why similar brain damage can affect each person differently.
The researchers used a unique research animal, a sea slug called Tritonia diomedea, to study this question. This animal was used because unlike humans, it has a small number of neurons and its behavior is simple. Despite this simplicity, the animals varied in how neurons were connected.
Under normal conditions, this variability did not matter to the animals’ behavior, but when a major pathway in the brain was severed, some of the animals showed little behavioral deficit, while others could not produce the behavior being studied. Remarkably, the researchers could artificially rewire the neural circuit using computer-generated connections and make animals susceptible or invulnerable to the injury.
“This study is important in light of the current Obama BRAIN initiative, which seeks to map all of the connections in the human brain,” said Georgia State professor, Paul Katz, who led the research project. “it shows that even in a simple brain, small differences that have no effect under normal conditions, have major implications when the nervous system is challenged by injury or trauma.”
Results of this study were published in the most recent edition of the journal eLife. The lead author on the study, Dr. Akira Sakurai, made this discovery in the course of doing basic research. He was assisted by Ph.D. student Arianna Tamvacakis from Dr. Katz’s lab.
(Source: news.gsu.edu)
Publication in Nature Showcases Most Comprehensive Wiring Diagram of the Mammalian Brain To Date
Researchers from the Allen Institute for Brain Science have published the first comprehensive, large-scale data set on how the brain of a mammal is wired, providing a groundbreaking data resource and fresh insights into how the nervous system processes information. Their landmark paper in this week’s issue of the journal Nature both describes the publicly available Allen Mouse Brain Connectivity Atlas, and demonstrates the exciting knowledge that can be gleaned from this valuable resource.
(Image: Connectivity Dot-o-Gram)
“Understanding how the brain is wired is among the most crucial steps to understanding how the brain encodes information,” explains Hongkui Zeng, Senior Director of Research Science at the Allen Institute for Brain Science. “The Allen Mouse Brain Connectivity Atlas is a standardized, quantitative, and comprehensive resource that will stimulate exciting investigations around the entire neuroscience community, and from which we have already gleaned unprecedented details into how structures are connected inside the brain.”
Using the data, Allen Institute scientists were able to demonstrate that there are highly specific patterns in the connections among different brain regions, and that the strengths of these connections vary with greater than five orders of magnitudes, balancing a small number of strong connections with a large number of weak connections. This publication comes just as the research team wraps up more than four years of work to collect and make publicly available the data behind the Allen Mouse Brain Connectivity Atlas project, with the completion of the Atlas announced in March 2014.
(Source: alleninstitute.org)
In the Human Brain, Size Really Isn’t Everything
There are many things that make humans a unique species, but a couple stand out. One is our mind, the other our brain.
The human mind can carry out cognitive tasks that other animals cannot, like using language, envisioning the distant future and inferring what other people are thinking.
The human brain is exceptional, too. At three pounds, it is gigantic relative to our body size. Our closest living relatives, chimpanzees, have brains that are only a third as big.
Scientists have long suspected that our big brain and powerful mind are intimately connected. Starting about three million years ago, fossils of our ancient relatives record a huge increase in brain size. Once that cranial growth was underway, our forerunners started leaving behind signs of increasingly sophisticated minds, like stone tools and cave paintings.
But scientists have long struggled to understand how a simple increase in size could lead to the evolution of those faculties. Now, two Harvard neuroscientists, Randy L. Buckner and Fenna M. Krienen, have offered a powerful yet simple explanation.
In our smaller-brained ancestors, the researchers argue, neurons were tightly tethered in a relatively simple pattern of connections. When our ancestors’ brains expanded, those tethers ripped apart, enabling our neurons to form new circuits.
Dr. Buckner and Dr. Krienen call their idea the tether hypothesis, and present it in a paper in the December issue of the journal Trends in Cognitive Sciences.
“I think it presents some pretty exciting ideas,” said Chet C. Sherwood, an expert on human brain evolution at George Washington University who was not involved in the research.
![Optogenetics as good as electrical stimulation
Neuroscientists are eagerly, but not always successfully, looking for proof that optogenetics – a celebrated technique that uses pulses of visible light to genetically alter brain cells to be excited or silenced – can be as successful in complex and large brains as it has been in rodent models.
A new study in the journal Current Biology may be the most definitive demonstration yet that the technique can work in nonhuman primates as well as, or even a little better than, the tried-and-true method of perturbing brain circuits with small bursts of electrical current. Brown University researchers directly compared the two techniques to test how well they could influence the visual decision-making behavior of two primates.
“For most of my colleagues in neuroscience to say ‘I’ll be able to incorporate [optogenetics] into my daily work with nonhuman primates,’ you have to get beyond ‘It does seem to sort of work’,” said study senior author David Sheinberg, professor of neuroscience professor affiliated with the Brown Institute for Brain Science. “In our comparison, one of the nice things is that in some ways we found quite analogous effects between electrical and optical [stimulation] but in the optical case it seemed more focused.”
Ultimately if it consistently proves safe and effective in the large, complex brains of primates, optogenetics could eventually be used in humans where it could provide a variety of potential diagnostic and therapeutic benefits.
Evidence in sight
With that in mind, Sheinberg, lead author Ji Dai and second author Daniel Brooks designed their experiments to determine whether and how much optical or electrical stimulation in a particular area of the brain called the lateral intraparietal area (LIP) would affect each subject’s decision making when presented with a choice between a target and a similar-looking, distracting character.
“This is an area of the brain involved in registering the location of salient objects in the visual world,” said Sheinberg who added that the experimental task was more cognitively sophisticated than those tested in optogenetics experiments in nonhuman primates before.
The main task for the subjects was to fixate on a central point in middle of the screen and then to look toward the letter “T” when it appeared around the edge of the screen. In some trials, they had to decide quickly between the T and a similar looking “+” or “†” character presented on opposite ends of the screen. They were rewarded if they glanced toward the T.
Before beginning those trials, the researchers had carefully placed a very thin combination sensor of an optical fiber and an electrode amid a small population of cells in the LIP of each subject. Then they mapped where on the screen an object should be in order for them to detect a response in those cells. They called that area the receptive field. With this information, they could then look to see what difference either optical or electrical stimulation of those cells would have on the subject’s inclination to look when the T or the distracting character appeared at various locations in visual space.
They found that stimulating with either method increased both subjects’ accuracy in choosing the target when it appeared in their receptive field. They also found the primates became less accurate when the distracting character appeared in their receptive field. Generally accuracy was unchanged when neither character was in the receptive field.
In other words, the stimulation of a particular group of LIP cells significantly biased the subjects to look at objects that appeared in the receptive field associated with those cells. Either stimulation method could therefore make the subjects more accurate or effectively distract them from making the right choice.
The magnitude of the difference made by either stimulation method compared to no stimulation were small, but statistically significant. When the T was in the receptive field, one research subject became 10 percentage points more accurate (80 percent vs. 70 percent) when optically stimulated and eight points more accurate when electrically stimulated. The subject was five points less accurate (73 percent vs. 78 percent) with optical stimulation and six percentage points less accurate with electrical stimulation when the distracting character was in the receptive field.
The other subject showed similar differences. In all, the two primates made thousands of choices over scores of sessions between the T and the distracting character with either kind of stimulation or none. Compared head-to-head in a statistical analysis, electrical and optical stimulation showed essentially similar effects in biasing the decisions.
Optical advantages
Although the two methods performed at parity on the main measure of accuracy, the optogenetic method had a couple of advantages, Sheinberg said.
Electrical stimulation appeared to be less precise in the cells it reached, a possibility suggested by a reduction in electrically stimulated subjects’ reaction time when the T appeared outside the receptive field. Optogenetic stimulation, Sheinberg said, did not produce such unintended effects.
Electrical stimulation also makes simultaneous electrical recording very difficult, Sheinberg said. That makes it hard to understand what neurons do when they are stimulated. Optogenetics, he said, allows for easier simultaneous electrical recording of neural activity.
Sheinberg said he is encouraged about using optogenetics to investigate even more sophisticated questions of cognition.
“Our goal is to be able to now expand this and use it again as a daily tool to probe circuits in more complicated paradigms,” Sheinberg said.
He plans a new study in which his group will look at memory of visual cues in the LIP.](http://40.media.tumblr.com/ce269cab39ef83d5b9dc806f444d1a2d/tumblr_mxqxr64tK51rog5d1o1_500.jpg)
Optogenetics as good as electrical stimulation
Neuroscientists are eagerly, but not always successfully, looking for proof that optogenetics – a celebrated technique that uses pulses of visible light to genetically alter brain cells to be excited or silenced – can be as successful in complex and large brains as it has been in rodent models.
A new study in the journal Current Biology may be the most definitive demonstration yet that the technique can work in nonhuman primates as well as, or even a little better than, the tried-and-true method of perturbing brain circuits with small bursts of electrical current. Brown University researchers directly compared the two techniques to test how well they could influence the visual decision-making behavior of two primates.
“For most of my colleagues in neuroscience to say ‘I’ll be able to incorporate [optogenetics] into my daily work with nonhuman primates,’ you have to get beyond ‘It does seem to sort of work’,” said study senior author David Sheinberg, professor of neuroscience professor affiliated with the Brown Institute for Brain Science. “In our comparison, one of the nice things is that in some ways we found quite analogous effects between electrical and optical [stimulation] but in the optical case it seemed more focused.”
Ultimately if it consistently proves safe and effective in the large, complex brains of primates, optogenetics could eventually be used in humans where it could provide a variety of potential diagnostic and therapeutic benefits.
Evidence in sight
With that in mind, Sheinberg, lead author Ji Dai and second author Daniel Brooks designed their experiments to determine whether and how much optical or electrical stimulation in a particular area of the brain called the lateral intraparietal area (LIP) would affect each subject’s decision making when presented with a choice between a target and a similar-looking, distracting character.
“This is an area of the brain involved in registering the location of salient objects in the visual world,” said Sheinberg who added that the experimental task was more cognitively sophisticated than those tested in optogenetics experiments in nonhuman primates before.
The main task for the subjects was to fixate on a central point in middle of the screen and then to look toward the letter “T” when it appeared around the edge of the screen. In some trials, they had to decide quickly between the T and a similar looking “+” or “†” character presented on opposite ends of the screen. They were rewarded if they glanced toward the T.
Before beginning those trials, the researchers had carefully placed a very thin combination sensor of an optical fiber and an electrode amid a small population of cells in the LIP of each subject. Then they mapped where on the screen an object should be in order for them to detect a response in those cells. They called that area the receptive field. With this information, they could then look to see what difference either optical or electrical stimulation of those cells would have on the subject’s inclination to look when the T or the distracting character appeared at various locations in visual space.
They found that stimulating with either method increased both subjects’ accuracy in choosing the target when it appeared in their receptive field. They also found the primates became less accurate when the distracting character appeared in their receptive field. Generally accuracy was unchanged when neither character was in the receptive field.
In other words, the stimulation of a particular group of LIP cells significantly biased the subjects to look at objects that appeared in the receptive field associated with those cells. Either stimulation method could therefore make the subjects more accurate or effectively distract them from making the right choice.
The magnitude of the difference made by either stimulation method compared to no stimulation were small, but statistically significant. When the T was in the receptive field, one research subject became 10 percentage points more accurate (80 percent vs. 70 percent) when optically stimulated and eight points more accurate when electrically stimulated. The subject was five points less accurate (73 percent vs. 78 percent) with optical stimulation and six percentage points less accurate with electrical stimulation when the distracting character was in the receptive field.
The other subject showed similar differences. In all, the two primates made thousands of choices over scores of sessions between the T and the distracting character with either kind of stimulation or none. Compared head-to-head in a statistical analysis, electrical and optical stimulation showed essentially similar effects in biasing the decisions.
Optical advantages
Although the two methods performed at parity on the main measure of accuracy, the optogenetic method had a couple of advantages, Sheinberg said.
Electrical stimulation appeared to be less precise in the cells it reached, a possibility suggested by a reduction in electrically stimulated subjects’ reaction time when the T appeared outside the receptive field. Optogenetic stimulation, Sheinberg said, did not produce such unintended effects.
Electrical stimulation also makes simultaneous electrical recording very difficult, Sheinberg said. That makes it hard to understand what neurons do when they are stimulated. Optogenetics, he said, allows for easier simultaneous electrical recording of neural activity.
Sheinberg said he is encouraged about using optogenetics to investigate even more sophisticated questions of cognition.
“Our goal is to be able to now expand this and use it again as a daily tool to probe circuits in more complicated paradigms,” Sheinberg said.
He plans a new study in which his group will look at memory of visual cues in the LIP.
Atypical brain circuits may cause slower gaze shifting in infants who later develop autism
Infants at 7 months of age who go on to develop autism are slower to reorient their gaze and attention from one object to another when compared to 7-month-olds who do not develop autism, and this behavioral pattern is in part explained by atypical brain circuits.
Those are the findings of a new study led by University of North Carolina School of Medicine researchers and published online March 20 by the American Journal of Psychiatry.
"These findings suggest that 7-month-olds who go on to develop autism show subtle, yet overt, behavioral differences prior to the emergence of the disorder. They also implicate a specific neural circuit, the splenium of the corpus callosum, which may not be functioning as it does in typically developing infants, who show more rapid orienting to visual stimuli," said Jed T. Elison, PhD, first author of the study.
Elison worked on the study, conducted as part of the Infant Brain Imaging Study (IBIS) Network, for his doctoral dissertation at UNC. He now is a postdoctoral fellow at the California Institute of Technology. The study’s senior author is Joseph Piven, MD, professor of psychiatry, director of the Carolina Institute for Developmental Disabilities at UNC, and the principle investigator of the IBIS Network.
The IBIS Network consists of research sites at UNC, Children’s Hospital of Philadelphia, Washington University in St. Louis, the University of Washington in Seattle, the University of Utah in Salt Lake City, and the Montreal Neurological Institute at McGill University, and the University of Alberta are currently recruiting younger siblings of children with autism and their families for ongoing research.
"Difficulty in shifting gaze and attention that we found in 7-month-olds may be a fundamental problem in autism," Piven said. "Our hope is that this finding may help lead us to early detection and interventions that could improve outcomes for individuals with autism and their families."
The study included 97 infants: 16 high-risk infants later classified with an autism spectrum disorder (ASD), 40 high-risk infants not meeting ASD criteria (i.e., high-risk-negative) and 41 low-risk infants. For this study, infants participated in an eye-tracking test and a brain scan at 7 months of age a clinical assessment at 25 months of age.
The results showed that the high-risk infants later found to have ASD were slower to orient or shift their gaze (by approximately 50 miliseconds) than both high-risk-negative and low-risk infants. In addition, visual orienting ability in low-risk infants was uniquely associated with a specific neural circuit in the brain: the splenium of the corpus callosum. This association was not found in infants later classified with ASD.
The study concluded that atypical visual orienting is an early feature of later emerging ASD and is associated with a deficit in a specific neural circuit in the brain.