Posts tagged neurons
Articles and news from the latest research reports.
Stimulating brain cells stops binge drinking, animal study finds
Researchers at the University at Buffalo have found a way to change alcohol drinking behavior in rodents, using the emerging technique of optogenetics, which uses light to stimulate neurons.
Their work could lead to powerful new ways to treat alcoholism, other addictions, and neurological and mental illnesses; it also helps explain the underlying neurochemical basis of drug addiction.
The findings, published in November in Frontiers in Neuroscience, are the first to demonstrate a causal relationship between the release of dopamine in the brain and drinking behaviors of animals. Research like this, which makes it possible to map the neuronal circuits responsible for specific behaviors, is a major focus of President Obama’s Brain Research for Advancing Innovative Neurotechnologies initiative, known as BRAIN.
In the experiments, rats were trained to drink alcohol in a way that mimics human binge-drinking behavior.
First author Caroline E. Bass, PhD, assistant professor of pharmacology and toxicology in the UB School of Medicine and Biomedical Sciences explains: “By stimulating certain dopamine neurons in a precise pattern, resulting in low but prolonged levels of dopamine release, we could prevent the rats from binging. The rats just flat out stopped drinking,” she says.
Bass’s co-authors are at Wake Forest University, where she worked previously.
Interestingly, the rodents continued to avoid alcohol even after the stimulation of neurons ended, she adds.
“For decades, we have observed that particular brain regions light up or become more active in an alcoholic when he or she drinks or looks at pictures of people drinking, for example, but we didn’t know if those changes in brain activity actually governed the alcoholic’s behavior,” says Bass.
The researchers activated the dopamine neurons through a type of deep brain stimulation, but unlike techniques now used to treat certain neurological disorders, such as severe tremors in Parkinson’s disease patients, this new technique, called optogenetics, uses light instead of electricity to stimulate neurons.
“Electrical stimulation doesn’t discriminate,” Bass explains. “It hits all the neurons, but the brain has many different kinds of neurons, with different neurotransmitters and different functions. Optogenetics allows you to stimulate only one type of neuron at a time.”
Bass specializes in using viral vectors to study the brain in substance abuse. In this study, she used a virus to introduce a gene encoding a light-responsive protein into the animals’ brains. That protein then activated a specific subpopulation of dopamine neurons in the brain’s reward system.
“I created a virus that will make this protein only in dopaminergic neurons,” Bass says.
The neuronal pathways affected in this research are involved in many neurological disorders, she says. For that reason, the results have application not only in understanding and treating alcohol-drinking behaviors in humans, but also in many devastating mental illnesses and neurological diseases that have a dopamine component.
Bass notes that this ability to target genes to dopamine neurons could potentially lead to the use of gene therapy in the brain to mitigate many of these disorders.
“We can target dopamine neurons in a part of the brain called the nigrostriatal pathway, which is what degenerates in Parkinson’s disease,” she says. “If we could infuse a viral vector into that part of the brain, we could target potentially therapeutic genes to the dopamine neurons involved in Parkinson’s. And by infusing the virus into other areas of the brain, we could potentially deliver therapeutic genes to treat other neurological diseases and mental illnesses, including schizophrenia and depression.”
Brain training works, but just for the practiced task
Search for “brain training” on the Web. You’ll find online exercises, games, software, even apps, all designed to prepare your brain to do better on any number of tasks. Do they work? University of Oregon psychologists say, yes, but “there’s a catch.”
The catch, according to Elliot T. Berkman, a professor in the Department of Psychology and lead author on a study published in the Jan. 1 issue of the Journal of Neuroscience, is that training for a particular task does heighten performance, but that advantage doesn’t necessarily carry over to a new challenge.
The training provided in the study caused a proactive shift in inhibitory control. However, it is not clear if the improvement attained extends to other kinds of executive function such as working memory, because the team’s sole focus was on inhibitory control, said Berkman, who directs the psychology department’s Social and Affective Neuroscience Lab.
"With training, the brain activity became linked to specific cues that predicted when inhibitory control might be needed," he said. "This result is important because it explains how brain training improves performance on a given task — and also why the performance boost doesn’t generalize beyond that task."
Sixty participants (27 male, 33 females and ranging from 18 to 30 years old) took part in a three-phase study. Change in their brain activity was monitored with functional magnetic resonance imaging (fMRI).
Half of the subjects were in the experimental group that was trained with a task that models inhibitory control — one kind of self-control — as a race between a “go” process and a “stop” process. A faster stop process indicates more efficient inhibitory control.
In each of a series of trials, participants were given a “go” signal — an arrow pointing left or right. Subjects pressed a key corresponding to the direction of the arrow as quickly as possible, launching the go process. However, on 25 percent of the trials, a beep sounded after the arrow appeared, signaling participants to withhold their button press, launching the stop process.
Participants practiced either the stop-signal task or a control task that didn’t affect inhibitory control every other day for three weeks. Performance improved more in the training group than in the control group.
Neural activity was monitored using functional magnetic resonance imaging (fMRI), which captures changes in blood oxygen levels, during a stop-signal task. MRI work was done in the UO’s Robert and Beverly Lewis Center for Neuroimaging. Activity in the inferior frontal gyrus and anterior cingulate cortex — brain regions that regulate inhibitory control — decreased during inhibitory control but increased immediately before it in the training group more than in the control group.
The fMRI results identified three regions of the brain of the trained subjects that showed changes during the task, prompting the researchers to theorize that emotional regulation may have been improved by reducing distress and frustration during the trials. Overall, the size of the training effect is small. A challenge for future research, they concluded, will be to identify protocols that might generate greater positive and lasting effects.”Researchers at the University of Oregon are using tools and technologies to shed new light on important mechanisms of cognitive functioning such as executive control,” said Kimberly Andrews Espy, vice president for research and innovation and dean of the UO Graduate School. “This revealing study on brain training by Dr. Berkman and his team furthers our understanding of inhibitory control and may lead to the design of better prevention tools to promote mental health.”
Motor Excitability predicts Working Memory
Humans with a high motor excitability have a better working memory than humans with a low excitability. This was shown in a study conducted by scientists from the Transfacultary Research Platform at the University of Basel. By measuring the motor excitability, conclusions can be drawn as to the general cortical excitability – as well as to cognitive performance.
Working memory allows the temporary storage of information such as memorizing a phone number for a short period of time. Studies in animals have shown that working memory processes among others depend on the excitability of neurons in the prefrontal cortex. Moreover, there is evidence that motor neuronal excitability might be related to the neuronal excitability of other cortical regions. Researchers from the Psychiatric University Clinics (UPK Basel) and the Faculty of Psychology in Basel have now studied if the excitability of the motor cortex correlates with working memory performance– results were positive.
«The motor cortical excitability can be easily studied with transcranial magnetic stimulation», says Nathalie Schicktanz, doctoral student and first author of the study. During this procedure, electromagnetic impulses with increasing intensity are applied over the motor cortex. For subjects with high motor excitability already weak impulses are sufficient to trigger certain muscles – such as those of the hand – to show a visible twitch.
Conclusions for other cortical regions
In the present study, that included 188 healthy young subjects, the scientists were able to show that subjects with a high motor excitability had increased working memory performance as compared to subjects with a low excitability. «By measuring the excitability of the motor cortex, conclusions can be drawn as to the excitability of other cortical areas», says Schicktanz.
«The findings help us to understand the importance of neuronal excitability for cognitive processes in humans», adds Dr. Kyrill Schwegler, co-author of the study. The results might also have important clinical implications, as working memory deficits are a component of many neuropsychiatric disorders, such as schizophrenia or attention deficit hyperactivity disorder. In a next step, the scientists plan to study the relation between neuronal excitability and memory on a molecular level.
The study is part of a project lead by Prof. Dominique de Quervain and Prof. Andreas Papassotiropoulos. The project uses transcranial magnetic stimulation to study the cognitive functions in humans. The goal is to identify the neurobiological and molecular mechanisms of human memory.
The logistics of learning
Learning requires constant reconfiguration of the connections between nerve cells. Two new studies now yield new insights into the molecular mechanisms that underlie the learning process.
Learning and memory are made possible by the incessant reorganization of nerve connections in the brain. Both processes are based on targeted modifications of the functional interfaces between nerve cells – the so-called synapses – which alter their form, molecular composition and functional properties. In effect, connections between cells that are frequently co-activated together are progressively altered so that they respond to subsequent signals more rapidly and more strongly. This way, information can be encoded in patterns of synaptic activity and promptly recalled when needed. The converse is also true: learned behaviors can be lost by disuse, because inactive synapses are themselves less likely to transmit an incoming impulse, leading to the decay of such connections.
How exactly an individual synapse is altered without simultaneously affecting nearby nerve cells or other synapses on the same cell is a question that is central to Michael Kiebler’s research. Kiebler, a biochemist, holds the Chair of Cell Biology in the Faculty of Medicine at LMU. “It is now clear that the changes take place in the cell that is stimulated by synaptic input – the post-synaptic cell – and in particular in its so-called dendritic spines,” he says, “and particles that are known as “neuronal RNA granules” deliver mRNA molecules to these sites“. These mRNAs represent the blueprints for the synthesis of the proteins responsible for reconfiguring the synapses. Kiebler‘s team has developed a model, which postulates that these granules migrate from dendrite to dendrite, and release their mRNAs specifically at sites that are repeatedly activated. This would ensure that the relevant proteins are synthesized only where they are needed within the cell.
In spite of the potential significance of the model, the molecular mechanisms required for its realization have remained obscure. mRNA-binding proteins, including Staufen2 (Stau2) and Barentsz, are essential components of the granules, and Kiebler’s team, in collaboration with Giulio Superti-Furga’s group (CeMM, Vienna), have now used specific antibodies to isolate and characterize neuronal granules that contain either Stau2 or Barentsz.
Surprising diversity
It has generally been assumed that all neuronal RNA granules have essentially similar compositions. However, the new findings indicate that this is not the case. A comparison between Stau2- and Barentsz-containing granules reveals that they differ in about two-thirds of their proteins. “This suggests that the RNA granules are highly heterogeneous and dynamic in their composition,” says Kiebler. “And that makes sense to me, because it would mean that the granules can perform different functions depending on which mRNAs they carry.” Furthermore, the researchers have shown that the granules contain virtually none of the factors known to promote the translation of mRNAs into proteins. On the contrary, they include many molecules that repress protein synthesis. This in turn implies that the process of mRNA transport is uncoupled from the subsequent production of the proteins they encode.
In a complementary study, Kiebler’s team also characterized the mRNA cargoes associated with the granules. “Until now, none of the RNA molecules present in Stau2-containing granules in mammalian nerve cells had been defined, but we have now been able to identify many specific mRNAs,” Kiebler explains. Further experiments revealed that Stau2 stabilizes the mRNAs, allowing them to be used more often for the production of proteins. Moreover, the researchers have shown that specialized structures within these mRNAs, called “Staufen-Recognized Structures” (SRS), are essential for their recognition and stabilization by Stau2. “This allows us to propose a molecular mechanism for RNA recognition for the first time,” says Kiebler.
Taken together, the two new papers (1, 2) provide novel insights into the molecular mechanisms that underlie learning and memory. The scientists now want to dissect out the details in future studies. “In the long term, we are particularly interested in the question of how an activated synapse can alter the state of the granules and induce the production of protein,” Kiebler notes. It is becoming increasingly clear that RNA-binding proteins play essential roles in nerve cells. Disruption of their action can lead to neurodegenerative diseases and neurological dysfunction. Clearly, not only classical conditions such as Alzheimer‘s or Parkinson’s disease, in which RNA-binding proteins are always involved, but also cognitive defects or age-associated impairment of learning ability must be viewed in this context,” Kiebler concludes.
(Source: en.uni-muenchen.de)
Brain Area Attacked by Alzheimer’s Links Learning and Rewards
One of the first areas of the brain to be attacked by Alzheimer’s disease is more active when the brain isn’t working very hard, and quiets down during the brain’s peak performance.
The question that Duke University graduate student Sarah Heilbronner wanted to resolve was whether this brain region, called the posterior cingulate cortex, or PCC, actively dampens cognitive performance, say by allowing the mind to wander, or is instead monitoring performance and trying to improve it when needed.
If the PCC were monitoring and improving performance, increased activity there would be the result of poor performance, not the cause of it.
The PCC connects to both learning and reward systems, Heilbronner said, and is a part of the “default mode network.” It lies along a mid-line between the ears, where many structures related to rewards can be found. “It’s kind of a nexus for multiple systems,” said Heilbronner, who is currently a postdoctoral researcher in neuroanatomy at the University of Rochester.
"As this area begins to deteriorate, people begin to show the early signs of cognitive decline — problems learning and remembering things, getting lost, trouble planning — that ultimately manifest as outright dementia," said Michael Platt, director of the Duke Institute for Brain Sciences, who supervised Heilbronner’s 2012 dissertation. Their findings appear Dec. 18 in the journal Neuron.
Heilbronner’s experiment to better understand the PCC’s role in learning and remembering relied on two rhesus macaque monkeys fitted with electrodes to read out the activity of individual neurons in their brains. Their task was akin to playing video games with their eyes. The monkeys were shown a series of photographs each day marked with dots at the upper left and lower right corners. To get a rewarding squirt of juice, they had to move their gaze to the correct target dot on a photo, and they learned by trial and error which dot would yield the reward for each photo.
Each day, they were shown up to 12 photos from an assortment of Heilbronner’s vacation snaps at Yellowstone National Park and the Grand Canyon. Some of each day’s images were familiar with a known reward target, and others were new. As the monkeys responded with their gaze, the researchers watched the activity of dozens of neurons in each monkey’s brain immediately following correct and incorrect responses. They also altered the amount of juice dispensed in some cases, creating a sense of high-reward and low-reward answers.
If the PCC actively dampened performance, the researchers would expect to see it active before a choice is made or the feedback is received. Instead, they saw it working after the feedback, lasting sometimes until the next image was presented. Neurons in the PCC responded strongly when the monkeys needed to learn something new, especially when they made errors or didn’t earn enough reward to keep motivated.
The researchers also ran the task after administering a drug, muscimol, that impaired the function of the PCC temporarily during testing. With the center inactivated by the drug, the monkeys could recall earlier learning regardless of the size of the reward. Learning a new item was still possible when the reward was large, but the monkeys couldn’t learn anything new when rewards were small. “Maybe it didn’t seem worth it,” Heilbronner said.
The dampening experiment also reinforced what the researchers had seen in the timing of the PCC’s response. If this center’s role is to let the mind wander, performance should have improved when the muscimol was administered, but the opposite was true.
Heilbronner concludes that the PCC summons more resources for a challenging cognitive task. So rather than being the cause of poor performance on a task, PCC actually steps in during a challenge to improve the situation.
"This study tells us that a healthy PCC is required for monitoring performance and keeping motivated during learning, particularly when problems are challenging," Platt said.
Heilbronner is now interested in finding out whether the PCC is more important to learning than it is to recall, and how motivation interacts with PCC abnormalities seen in Alzheimer’s disease.
Neurons subtract images and use the differences
Efficient reduction of data volumes
Researchers have hitherto assumed that information supplied by the sense of sight was transmitted almost in its entirety from its entry point to higher brain areas, across which visual sensation is generated. “It was therefore a surprise to discover that the data volumes are considerably reduced as early as in the primary visual cortex, the bottleneck leading to the cerebrum,” says PD Dr Dirk Jancke from the Institute for Neural Computation at the Ruhr-Universität. “We intuitively assume that our visual system generates a continuous stream of images, just like a video camera. However, we have now demonstrated that the visual cortex suppresses redundant information and saves energy by frequently forwarding image differences.”
Plus or minus: the brain’s two coding strategies
The researchers recorded the neurons’ responses to natural image sequences, for example vegetation landscapes or buildings. They created two versions of the images: a complete one and one in which they had systematically removed certain elements, specifically vertical or horizontal contours. If the time elapsing between the individual images was short, i.e. 30 milliseconds, the neurons represented complete image information. That changed when the time elapsing in the sequences was longer than 100 milliseconds. Now, the neurons represented only those elements that were new or missing, namely image differences. “When we analyse a scene, the eyes perform very fast miniature movements in order to register the fine details,” explains Nora Nortmann, postgraduate student at the Institute of Cognitive Science at the University of Osnabrück and the RUB work group Optical Imaging. The information regarding those details are forwarded completely and immediately by the primary visual cortex. “If, on the other hand, the time elapsing between the gaze changes is longer, the cortex codes only those aspects in the images that have changed,” continues Nora Nortmann. Thus, certain image sections stand out and interesting spots are easier to detect, as the researchers speculate.
“Our brain is permanently looking into the future”
This study illustrates how activities of visual neurons are influenced by past events. “The neurons build up a short-term memory that incorporates constant input,” explains Dirk Jancke. However, if something changes abruptly in the perceived image, the brain generates a kind of error message on the basis of the past images. Those signals do not reflect the current input, but the way the current input deviates from the expectations. Researchers have hitherto postulated that this so-called predictive coding only takes place in higher brain areas. “We demonstrated that the principle applies for earlier phases of cortical processing, too,” concludes Jancke. “Our brain is permanently looking into the future and comparing current input with the expectations that arose based on past situations.”
Observing brain activities in millisecond range
In order to monitor the dynamics of neuronal activities in the brain in the millisecond range, the scientists used voltage-dependent dyes. Those substances fluoresce when neurons receive electrical impulses and become active. Thanks to a high-resolution camera system and the subsequent computer-aided analysis, the neuronal activity can be measured across a surface of several square millimetres. The result is a temporally and spatially precise film of transmission processes within neuronal networks.
Bibliographic record
N. Nortmann, S. Rekauzke, S. Onat, P. König, D. Jancke (2013): Primary visual cortex represents the difference between past and present, Cerebral Cortex
Silencing Synapses: Research Team Finds Hope for Pharmacological Solution to Cocaine Addiction
Imagine kicking a cocaine addiction by simply popping a pill that alters the way your brain processes chemical addiction. New research from the University of Pittsburgh suggests that a method of biologically manipulating certain neurocircuits could lead to a pharmacological approach that would weaken post-withdrawal cocaine cravings. The findings have been published in Nature Neuroscience.
Researchers led by Pitt neuroscience professor Yan Dong used rat models to examine the effects of cocaine addiction and withdrawal on nerve cells in the nucleus accumbens, a small region in the brain that is commonly associated with reward, emotion, motivation, and addiction. Specifically, they investigated the roles of synapses—the structures at the ends of nerve cells that relay signals.
When an individual uses cocaine, some immature synapses are generated, which are called “silent synapses” because they send few signals under normal physiological conditions. After that individual quits using cocaine, these “silent synapses” go through a maturation phase and acquire the ability to send signals. Once they can send signals, the synapses will send craving signals for cocaine if the individual is exposed to cues that previously led him or her to use the drug.
The researchers hypothesized that if they could reverse the maturation of the synapses, the synapses would remain silent, thus rendering them unable to send craving signals. They examined a chemical receptor known as CP-AMPAR that is essential for the maturation of the synapses. In their experiments, the synapses reverted to their silent states when the receptor was removed.
“Reversing the maturation process prevents the intensification process of cocaine craving,” said Dong, the study’s corresponding author and assistant professor of neuroscience in Pitt’s Kenneth P. Dietrich School of Arts and Sciences. “We are now developing strategies to maintain the ‘reversal’ effects. Our goal is to develop biological and pharmacological strategies to produce long-lasting de-maturation of cocaine-generated silent synapses.”
(Source: news.pitt.edu)
Tinnitus discovery opens door to possible new treatment avenues
For tens of millions of Americans, there’s no such thing as the sound of silence. Instead, even in a quiet room, they hear a constant ringing, buzzing, hissing, humming or other noise in their ears that isn’t real. Called tinnitus, it can be debilitating and life-altering.
Now, University of Michigan Medical School researchers report new scientific findings that help explain what is going on inside these unquiet brains.
The discovery reveals an important new target for treating the condition. Already, the U-M team has a patent pending and device in development based on the approach.
The critical findings are published online in the prestigious Journal of Neuroscience. Though the work was done in animals, it provides a science-based, novel approach to treating tinnitus in humans.
Susan Shore, Ph.D., the senior author of the paper, explains that her team has confirmed that a process called stimulus-timing dependent multisensory plasticity is altered in animals with tinnitus – and that this plasticity is “exquisitely sensitive” to the timing of signals coming in to a key area of the brain.
That area, called the dorsal cochlear nucleus, is the first station for signals arriving in the brain from the ear via the auditory nerve. But it’s also a center where “multitasking” neurons integrate other sensory signals, such as touch, together with the hearing information.
Shore, who leads a lab in U-M’s Kresge Hearing Research Institute, is a Professor of Otolaryngology and Molecular and Integrative Physiology at the U-M Medical School, and also Professor of Biomedical Engineering, which spans the Medical School and College of Engineering.
She explains that in tinnitus, some of the input to the brain from the ear’s cochlea is reduced, while signals from the somatosensory nerves of the face and neck, related to touch, are excessively amplified.
“It’s as if the signals are compensating for the lost auditory input, but they overcompensate and end up making everything noisy,” says Shore.
The new findings illuminate the relationship between tinnitus, hearing loss and sensory input and help explain why many tinnitus sufferers can change the volume and pitch of their tinnitus’s sound by clenching their jaw, or moving their head and neck.
But it’s not just the combination of loud noise and overactive somatosensory signals that are involved in tinnitus, the researchers report.
It’s the precise timing of these signals in relation to one another that prompt the changes in the nervous system’s plasticity mechanisms, which may lead to the symptoms known to tinnitus sufferers.
Shore and her colleagues, including former U-M biomedical engineering graduate student and first author Seth Koehler, Ph.D., hope their findings will eventually help many of the 50 million people in the United States and millions more worldwide who have the condition, according to the American Tinnitus Association. They hope to bring science-based approaches to the treatment of a condition for which there is no cure – and for which many unproven would-be therapies exist.
Tinnitus especially affects baby boomers, who, as they reach an age at which hearing tends to diminish, increasingly experience tinnitus. The condition most commonly occurs with hearing loss, but can also follow head and neck trauma, such as after an auto accident, or dental work.
Loud noises and blast forces experienced by members of the military in war zones also can trigger the condition. Tinnitus is a top cause of disability among members and veterans of the armed forces.
Researchers still don’t understand what protective factors might keep some people from developing tinnitus, while others exposed to the same conditions experience tinnitus.
In this study, only half of the animals receiving a noise-overexposure developed tinnitus. This is similarly the case with humans — not everyone with hearing damage ends up with tinnitus. An important finding in the new paper is that animals that did not get tinnitus showed fewer changes in their multisensory plasticity than those with evidence of tinnitus. In other words, their neurons were not hyperactive.
Shore is now working with other students and postdoctoral fellows to develop a device that uses the new knowledge about the importance of signal timing to alleviate tinnitus. The device will combine sound and electrical stimulation of the face and neck in order to return to normal the neural activity in the auditory pathway.
“If we get the timing right, we believe we can decrease the firing rates of neurons at the tinnitus frequency, and target those with hyperactivity,” says Shore. She and her colleagues are also working to develop pharmacological manipulations that could enhance stimulus timed plasticity by changing specific molecular targets.
But, she notes, any treatment will likely have to be customized to each patient, and delivered on a regular basis. And some patients may be more likely to derive benefit than others.
Synaptic mechanisms of brain waves
Team at IST Austria examines synaptic mechanisms of rhythmic brain waves • Achievement possible through custom-design tools developed in collaboration with the institute’s Miba machine shop
How information is processed and encoded in the brain is a central question in neuroscience, as it is essential for high cognitive function such as learning and memory. Theta-gamma oscillations are “brain waves” observed in the hippocampus of behaving rats, a brain region involved in learning and memory. In rodents, theta-gamma oscillations are associated with information processing during exploration and spatial navigation. However, the underlying synaptic mechanisms have so far remained unclear. In research published this week in the journal Neuron, postdoc Alejandro Pernía-Andrade and Professor Peter Jonas, both at the Institute of Science and Technology Austria (IST Austria), discovered the synaptic mechanisms underlying oscillations at the dentate gyrus (main entrance of the hippocampus). Furthermore, the researchers suggest a role for these oscillations in the coding of information by the dentate gyrus principal neurons. Thus, these findings contribute to a better understanding of how information is processed in the brain.
Brain oscillations are, in fact, rhythmic changes in voltage in the extracellular space, referred to as electrical brain signals associated with the processing of information. These electrical signals are similar to those seen in electro-encephalographic recordings (EEG) in humans. Pernía-Andrade and Jonas observed these oscillations in a brain region called the hippocampus in behaving rats, and recorded oscillations occurring in this area using extracellular probes. To understand how oscillations are generated and which synaptic events trigger these oscillations, the researchers looked at synaptic transmission in granule cells (principal cells at the main entrance of the hippocampus) from both the extracellular (oscillations) and the intracellular perspectives (synaptic currents and neuronal firing), and then correlated the two. They discovered that excitatory and inhibitory synaptic signals contributed to different frequencies of oscillations, with excitation from the entorhinal cortex generating theta oscillations and inhibition by local dentate gyrus interneurons generating gamma oscillations. Together, excitation and inhibition provide the rhythmic signals of oscillations. It has been speculated that oscillations may help the dentate gyrus to encode information by acting as reference signals in temporal coding. Pernía-Andrade and Jonas now show that granule cell neurons send signals only at specific times in the cycle of oscillations. This so-called “phase locking” is necessary if oscillations are to function as reference signals in temporal coding.
The precise, high-resolution recording from granule cells necessary for these discoveries was possible only through technological innovations by Pernía-Andrade and Jonas, as previously no equipment was available to record synaptic signals in active rats in such high resolution. They are the result of a collaboration with the Miba machine shop, IST Austria’s electrical and mechanical SSU (Scientific Service Unit). Adapting commercially available equipment and custom-designing tools, Pernía-Andrade, Jonas and Todor Asenov, manager of the Miba machine shop, produced the first tools for precise biophysical analysis in active rats. This research is therefore not only a scientific advance but also represents a significant technological and conceptual progress in the quest to understand neuronal behavior under natural conditions.
(Source: ist.ac.at)
Researchers Study Alcohol Addiction Using Optogenetics
Wake Forest Baptist Medical Center researchers are gaining a better understanding of the neurochemical basis of addiction with a new technology called optogenetics.
In neuroscience research, optogenetics is a newly developed technology that allows researchers to control the activity of specific populations of brain cells, or neurons, using light. And it’s all thanks to understanding how tiny green algae, that give pond scum its distinctive color, detect and use light to grow.
The technology enables researchers like Evgeny A. Budygin, Ph.D., assistant professor of neurobiology and anatomy at Wake Forest Baptist, to address critical questions regarding the role of dopamine in alcohol drinking-related behaviors, using a rodent model.
"With this technique, we’ve basically taken control of specific populations of dopamine cells, using light to make them respond - almost like flipping a light switch," said Budygin. "These data provide us with concrete direction about what kind of patterns of dopamine cell activation might be most effective to target alcohol drinking."
The latest study from Budygin and his team published online in last month’s journal Frontiers in Behavioral Neuroscience. Co-author Jeffrey L. Weiner, Ph.D., professor of physiology and pharmacology at Wake Forest Baptist, said one of the biggest challenges in neuroscience has been to control the activity of brain cells in the same way that the brain actually controls them. With optogenetics, neuroscientists can turn specific neurons on or off at will, proving that those neurons actually govern specific behaviors.
"We have known for many years what areas of the brain are involved in the development of addiction and which neurotransmitters are essential for this process," Weiner said. "We need to know the causal relationship between neurochemical changes in the brain and addictive behaviors, and optogenetics is making that possible now."
The researchers used cutting-edge molecular techniques to express the light-responsive channelrhodopsin protein in a specific population of dopamine cells in the brain-reward system of rodents. They then implanted tiny optical fibers into this brain region and were able to control the activity of these dopamine cells by flashing a blue laser on them.
"You can place an electrode in the brain and apply an electrical current to mimic the way brain cells get excited, but when you do that you’re activating all the cells in that area," Weiner said. "With optogenetics, we were able to selectively control a specific population of dopamine cells in a part of the brain-reward system. Using this technique, we discovered distinct patterns of dopamine cell activation that seemed to be able to disrupt the alcohol-drinking behavior of the rats."
Weiner said there is translational value from the study because “it gives us better insight into how we might want to use something like deep-brain stimulation to treat alcoholism. Doctors are starting to use deep-brain stimulation to treat everything from anxiety to depression, and while it works, there is little scientific understanding behind it, he said.
Budygin agreed and said this kind of project wouldn’t be possible without cross campus collaboration between neurobiology and anatomy, physiology and pharmacology and physics. “Now we are taking the first steps in this direction,” he said. “It was impossible before the optogenetic era.”