Posts tagged cerebellum
Articles and news from the latest research reports.
Discovery Shows Cerebellum Plays Important Role In Sensing Limb Position And Movement
Kennedy Krieger Institute researchers find that damage to the cerebellum impairs ability to predict motion outcomes and discrimination between limb positions.
Researchers at the Kennedy Krieger Institute announced today study findings showing, for the first time, the link between the brain’s cerebellum and proprioception, or the body’s ability to sense movement and joint and limb position. Published in The Journal of Neuroscience, the study uncovers a previously unknown perceptual deficit among cerebellar patients, suggesting that damage to this portion of the brain can directly impact a person’s ability to sense the position of their limbs and predict movement. This discovery could prompt future researchers to reexamine physical therapy tactics for cerebellar patients, who often have impaired coordination or appear clumsy.
The sense of proprioception arises from the brain’s readout of signals from receptors in muscles, joints and ligaments, but also from the brain’s predictions of how motor commands will move the limb. The latter can only contribute to proprioception when a person actively moves their own body. To date, researchers and neurologists believed that proprioception did not occur in the cerebellum, and thus, damage to the cerebellum did not affect proprioception.
“Proprioception was previously not considered a factor in the therapy or recovery of cerebellar patients. In fact, previous research has shown that individuals with cerebellum damage and no other clinical neurological impairments have normal proprioception when their limbs are moved passively in a clinical setting,” says Amy J. Bastian, Ph.D., PT, director of the Motion Analysis Laboratory at Kennedy Krieger Institute. “However, when these patients move their limbs actively, they exhibit significant proprioceptive impairment.”
Additionally, researchers found that proprioception in healthy subjects was impaired when unpredictable dynamics, or small disturbances to the cerebellum, were incorporated into active movement. This suggests that muscle activity alone is likely insufficient to improve perception of limb placement, and proprioception should be taken into consideration when determining therapeutic practices for cerebellar patients.
Study Results and Methodology
The study compared 11 healthy people (control group) to 11 patients with cerebellar damage (caused by spinocerebellar ataxia, sporadic cerebellar ataxia or autosomal-dominant cerebellar ataxia type III) but no evidence of white matter damage, spontaneous nystagmus or atrophy to the brainstem. None of the patients included in the study had sensory loss assessed by conventional clinical measures of proprioception and tactile sensation.
Participants were compared in three psychophysical tasks designed to assess passive proprioception, active proprioception with simple dynamics, and active proprioception with complex, unpredictable dynamics designed to disrupt the cerebellum. All tasks relied on proprioceptive sense without vision.
Results showed that:
- Cerebellar patients had no deficits in passive proprioception
- Unlike control subjects, cerebellar patients did not show an improvement between passive and active proprioception with simple dynamics
- Control patients performed similarly to patients in an active proprioception task with unpredictable, small disruptions to their movement.
This study was supported by the Kennedy Krieger Institute, the Johns Hopkins University and the National Institutes of Health.
Centers throughout the brain work together to make reading possible
A combination of brain scans and reading tests has revealed that several regions in the brain are responsible for allowing humans to read.
The findings open up the possibility that individuals who have difficulty reading may only need additional training for specific parts of the brain — targeted therapies that could more directly address their individual weaknesses.
“Reading is a complex task. No single part of the brain can do all the work,” said Qinghua He, postdoctoral research associate at the USC Brain and Creativity Institute, based at the USC Dornsife College of Letters, Arts and Sciences, and first author of a study on this research that was published in The Journal of Neuroscience on July 31.
The study looked at the correlation between reading ability and brain structure revealed by high-resolution magnetic resonance imaging (MRI) scans of more than 200 participants.
To control for external factors, the participants were about the same age and education level (college students); right-handed (lefties use the opposite hemisphere of their brain for reading); and all had about the same language skills (Chinese-speaking, with English as a second language for more than nine years). Their IQ, response speed and memory were also tested.
The study first collected data for seven different reading tests of a sample of more than 400 participants. These tests were intended to explore three aspects of their reading ability: phonological decoding ability (the ability to sound out printed words); form-sound association (how well participants could make connections between a new word and sound); and naming speed (how quickly participants were able to read out loud).
Each of these aspects, it turned out, was related to the gray matter volume — the amount of neurons — in different parts of the brain.
The MRI analysis showed that phonological decoding ability was strongly connected with gray matter volume in the left superior parietal lobe (around the top/rear of the brain); form-sound association was strongly connected with the hippocampus and cerebellum; and naming speed lit up a variety of locations around the brain.
“Our results strongly suggest that reading consists of unique capacities and is supported by distinct neural systems that are relatively independent of general cognitive abilities,” said Gui Xue, corresponding author of the study. Xue was formerly a research assistant professor at USC and now is a professor and director of the Center for Brain and Learning Sciences at Beijing Normal University.
“Although there is no doubt that reading has to build up existing neural systems due to the short history of written language in human evolution, years of reading experiences might have finely tuned the system to accommodate the specific requirement of a given written system,” Xue said.
He and Xue collaborated with Chunhui Chen and Qi Dong of Beijing Normal University; Chuansheng Chen of the University of California, Irvine; and Zhong-Lin Lu of Ohio State University.
One of the top features of this study was its unusually wide sample size, according to researchers. Typically, MRI studies test a relatively small sample of individuals — perhaps around 20 to 30 — because of the high cost of using the MRI machine. Testing a single individual can cost about $500, depending on the nature of the research.
The team had the good fortune of receiving access to Beijing Normal University’s new MRI center — the BNU Imaging Center for Brain Research — just before it opened to the public. With support from several grants, the researchers were able to conduct MRI tests on 233 individuals.
Next, the group will explore how to combine data from other factors, such as white matter, resting and task functional MRI, as well as more powerful machine-learning techniques, to improve the accuracy of individuals’ reading abilities.
“Research along this line will enable the early diagnosis of reading difficulties and the development of more targeted therapies,” Xue said.
Keeping your balance
It happens to all of us at least once each winter in Montreal. You’re walking on the sidewalk and before you know it you are slipping on a patch of ice hidden under a dusting of snow. Sometimes you fall. Surprisingly often you manage to recover your balance and walk away unscathed. McGill researchers now understand what’s going on in the brain when you manage to recover your balance in these situations. And it is not just a matter of good luck.
Prof. Kathleen Cullen and her PhD student Jess Brooks of the Dept of Physiology have been able to identify a distinct and surprisingly small cluster of cells deep within the brain that react within milliseconds to readjust our movements when something unexpected happens, whether it is slipping on ice or hitting a rock when skiing. What is astounding is that each individual neuron in this tiny region that is smaller than a pin’s head displays the ability to predict and selectively respond to unexpected motion.
This finding both overturns current theories about how we learn to maintain our balance as we move through the world, and also has significant implications for understanding the neural basis of motion sickness.
Scientists have theorized for some time that we fine-tune our movements and maintain our balance, thanks to a neural library of expected motions that we gain through “sensory conflicts” and errors. “Sensory conflicts” occur when there is a mismatch between what we think will happen as we move through the world and the sometimes contradictory information that our senses provide to us about our movements.
This kind of “sensory conflict” may occur when our bodies detect motion that our eyes cannot see (such as during plane, ocean or car travel), or when our eyes perceive motion that our bodies cannot detect (such as during an IMAX film, when the camera swoops at high speed over the edge of steep cliffs and deep into gorges and valleys while our bodies remain sitting still). These “sensory conflicts” are also responsible for the feelings of vertigo and nausea that are associated with motion sickness.
But while the areas of the brain involved in estimating spatial orientation have been identified for some time, until now, no one has been able to either show that distinct neurons signaling “sensory conflicts” existed, nor demonstrate exactly how they work. “We’ve known for some time that the cerebellum is the part of the brain that takes in sensory information and then causes us to move or react in appropriate ways,” says Prof. Cullen. “But what’s really exciting is that for the first time we show very clearly how the cerebellum selectively encodes unexpected motion, to then send our body messages that help us maintain our balance. That it is such a very exact neural calculation is exciting and unexpected.”
By demonstrating that these “sensory conflict” neurons both exist and function by making choices “on the fly” about which sensory information to respond to, Cullen and her team have made a significant advance in our understanding of how the brain works to keep our bodies in balance as we move about.
The research was done by recording brain activity in macaque monkeys who were engaged in performing specific tasks while at the same time being unexpectedly moved around by flight-simulator style equipment.
(Source: eurekalert.org)
Newly understood circuits add finesse to nerve signals
An unusual kind of circuit fine-tunes the brain’s control over movement and incoming sensory information, and without relying on conventional nerve pathways, according to a study published this week in the journal Neuron.
Researchers at the University of Alabama at Birmingham (UAB) discovered new details of a mechanism operating in the cerebellum, the brain region that processes nerve signals coming in from the spinal cord and cortex.
“Our results explain a second layer of nerve signal transmission that depends, not on whether a nerve cell is wired into a defined signaling pathway circuit, but instead on how close it is to the pathway,” said Jacques Wadiche, Ph.D., assistant professor in the Department of Neurobiology within the UAB School of Medicine, investigator in the Evelyn McKnight Brain Institute at UAB and senior study author. “It has become clear that this kind of nerve circuit is intimately linked with autism and certain movement disorders, and we hope the mechanisms detailed here contribute to the design of new treatments.”
Beyond nerve pathways
Nerve cells are known to occur in defined pathways that transmit messages in one direction. This pathway-specific view of nerve signaling has been reinforced by high-tech imaging studies yielding detailed connectivity maps. Along these lines, the Obama Administration will soon ask Congress for $100 million in research funding to further improve such maps.
Within nerve pathways, each nerve cell sends an electric pulse down an extension of itself called an axon until it reaches a synapse, a gap between itself and the next cell in line. When it reaches an axon’s end, the pulse triggers the release of chemicals called neurotransmitters that float across the gap, where they either cause the downstream nerve cell to “fire” and pass on the message, or stop the message. In this way, each synapse between nerve cells in a pathway “decides” whether or not a message continues on.
In recent years, studies have found that neurotransmitters also spill into tissue surrounding axons in a type signaling not restricted to synaptic connections. With the term itself implying a mess, “spillover” was thought to degrade the capacity of nerve cells to precisely pass on signals.
The current study adds to recent evidence arguing that spillover may instead enhance message transmission, with the results revolving around three nerve cell types in the cerebellum: climbing fibers, Purkinje cells and interneurons.
Climbing fibers, which carry information from the brainstem into the cerebellum, play key roles in motor timing and sensory processing. Within these fibers, nerve cells release the excitatory neurotransmitter glutamate into synapses that then strive to pass messages deeper into the cerebellum. Purkinje cells are paired with climbing fibers and intent on inhibiting their signals.
When excited by glutamate from climbing fibers at one end, Purkinje cells release another neurotransmitter called GABA at their downstream synapse to stop the message. An excitatory signal triggers an inhibitory one as a counter-balance, a form of feedback critical to the function of the central nervous system. Lack of inhibition, for instance, causes circuits to seize, seizures and the death of Purkinje cells, the latter of which has been linked by post mortem studies to a higher incidence of autism spectrum disorders.
Previously, researchers thought that incoming signals from climbing fibers caused a single, strong response in the cerebellum: the activation of Purkinje cells that released GABA. The current study argues that such signals also trigger the firing of interneurons, nearby inhibitory middlemen that connect sets of nerve cells.
Interneurons within, and outside of, the glutamate spill zone around climbing fibers may have different effects on the other interneurons and Purkinje cells they connect to, according to the current finding. The interactions either inhibit or excite many Purkinje cells surrounding an active climbing fiber and refine its messages in a feedback system more sophisticated than once thought.
Glutamate has its effect by fitting into AMPA and NMDA receptor proteins, like a key into a lock, on the surfaces of nerve cells it signals to. The consensus has been that glutamate receptors occur only within synapses. Finding them on nerve cells outside of synapse-defined pathways represents “a fundamental shift in understanding,” said Wadiche, and may result in longer-lasting inhibition within key signaling pathways.
“A 2007 study published in Nature Neuroscience found that many climbing fibers signal to interneurons in the outer layer of the cerebellum outside nerve pathways and exclusively through glutamate spillover,” said Luke Coddington, a graduate student in Wadiche’s lab and study author. “Our team built on that observation to show how spillover affects the function of interneurons, Purkinje cells, and ultimately, the entire cerebellum. Spillover-mediated signaling recruits local microcircuits to extend the reach and finesse of climbing fiber signaling.”
A pan-European study: signs of motor disorders can appear years before disease manifestation
It is known that signs of neurological disorders such as Alzheimer’s and Huntington’s disease can appear years before the disease becomes manifest; these signs take the form of subtle changes in the brain and behavior of individuals affected. For the first time, an international group of researchers led by the DZNE and the Bonn University Hospital has proven the existence of such signatures for motor disorders belonging to the group of “spinocerebellar ataxias”. The scientists report these findings in the current online edition of “The Lancet Neurology”. This pan-European study could open up new possibilities of early diagnosis and smooth the way for treatments which tackle diseases before the patient’s nervous system is irreparably damaged.
“Spinocerebellar ataxias” comprise a group of genetic diseases of the cerebellum and other parts of the brain. Persons affected only have limited control of their muscles. They also suffer from balance disorders and impaired speech. The symptoms originate from mutations in the patient’s genetic make-up. These cause nerve cells to become damaged and to die off. Such genetic defects are comparatively rare: it is estimated that about 3,000 people in Germany are affected.
It is known that there are various subtypes of these neurodegenerative diseases. The age at which the symptoms manifest consequently fluctuates between about 30 and 50. “Our aim was to find out whether specific signs can be recognized before a disease becomes obvious,” says project leader Prof. Thomas Klockgether, Director for Clinical Research at the DZNE and Director of the Clinic for Neurology at Bonn University Hospital.
Pan-European cooperation
The study, which involved 14 research centers in all, focused on the four most common forms of spinocerebellar ataxia. These account for more than half of all cases. More than 250 siblings and children of patients throughout Europe declared their willingness to participate in appropriate tests. These individuals had no obvious symptoms of ataxia. However, about half of them had inherited the genetic defects which invariably cause the disease to manifest in the long term.
With the aid of a mathematical model that considered the genetic mutations and their effects, the scientists were able to estimate the time remaining until the disease could be expected to manifest. In the test group, this “time to onset” varied from 2 to 24 years. These and all other test results remained anonymous: the data was not known to the test subjects, neither could the researchers assign it to specific participants. The same applied to individuals whose DNA turned out to be inconspicuous. “People in families with cases of ataxia usually have not taken a genetic test and they don’t want to know any results. This kind of information has to be treated very carefully for ethical reasons,” emphasizes Klockgether.
Extensive tests
The study participants made themselves available for various examinations including standardized tests of muscular coordination. These included measuring the time needed by the subjects to walk a specific distance. Another series of experiments involved inserting small pins into the holes of a board and taking them back out as quickly as possible. Yet another test measured how often the participants could repeat a certain sequence of syllables in ten seconds. “The tests were designed in such a way that they would provide significant information but still be easy to perform,” says Klockgether. “Tests like these can be performed anywhere without need for special technology.”
Technically complex methods were also used: all study participants were tested for the genetic defects relevant to ataxia. At some of the research centers involved in the study, it was also possible to examine the subjects with the aid of magnetic resonance imaging (MRI). This enabled researchers to measure the total brain volume as well as the dimensions of individual parts of the brain in about a third of the subjects.
Notable findings
In two of the four types of ataxia investigated, the scientists found signs of impending disease. “We found a loss in brain volume, particularly shrinkage in the area of the cerebellum and brain stem. These subjects also had subtle difficulties with coordination,” Klockgether summarizes the results. “This means that manifestations of this kind can be measured years before the disease is likely to become obvious.”
The findings for the other two types of ataxia were less conclusive. “I assume that there are indications also for these types of the disease. However, this subgroup of participants was relatively small. It is therefore difficult to make statistically reliable statements about these subjects,” says the Bonn-based researcher.
In his view, the study results testify to the modern-day view of neurodegenerative processes: “Neurodegeneration doesn’t begin when the symptoms surface. Rather, it is a stealthy disease which starts developing years or even decades beforehand.”
Klockgether believes that this gradual development offers certain opportunities: “If we intervened in this process by appropriate treatments and at a sufficiently early stage, it might be possible to slow down or even stop the disease process.”
More investigations planned
The current results will be the basis for long-term investigations. A new series of tests with the same group of individuals has already started; further tests are scheduled every two years. The scientists intend to monitor the study participants for as long as possible.
(Source: dzne.de)
Brain frontal lobes not sole centre of human intelligence
Human intelligence cannot be explained by the size of the brain’s frontal lobes, say researchers.
Research into the comparative size of the frontal lobes in humans and other species has determined that they are not - as previously thought - disproportionately enlarged relative to other areas of the brain, according to the most accurate and conclusive study of this area of the brain.
It concludes that the size of our frontal lobes cannot solely account for humans’ superior cognitive abilities.
The study by Durham and Reading universities suggests that supposedly more ‘primitive’ areas, such as the cerebellum, were equally important in the expansion of the human brain. These areas may therefore play unexpectedly important roles in human cognition and its disorders, such as autism and dyslexia, say the researchers.
The study is published in the Proceedings of the National Academy of Sciences (PNAS) today.
The frontal lobes are an area in the brain of mammals located at the front of each cerebral hemisphere, and are thought to be critical for advanced intelligence.
Lead author Professor Robert Barton from the Department of Anthropology at Durham University, said: “Probably the most widespread assumption about how the human brain evolved is that size increase was concentrated in the frontal lobes.
"It has been thought that frontal lobe expansion was particularly crucial to the development of modern human behaviour, thought and language, and that it is our bulging frontal lobes that truly make us human. We show that this is untrue: human frontal lobes are exactly the size expected for a non-human brain scaled up to human size.
"This means that areas traditionally considered to be more primitive were just as important during our evolution. These other areas should now get more attention. In fact there is already some evidence that damage to the cerebellum, for example, is a factor in disorders such as autism and dyslexia."
The scientists argue that many of our high-level abilities are carried out by more extensive brain networks linking many different areas of the brain. They suggest it may be the structure of these extended networks more than the size of any isolated brain region that is critical for cognitive functioning.
Previously, various studies have been conducted to try and establish whether humans’ frontal lobes are disproportionately enlarged compared to their size in other primates such as apes and monkeys. They have resulted in a confused picture with use of different methods and measurements leading to inconsistent findings.
The Durham and Reading researchers, funded by The Leverhulme Trust, analysed data sets from previous animal and human studies using phylogenetic, or ‘evolutionary family tree’, methods, and found consistent results across all their data. They used a new method to look at the speed with which evolutionary change occurred, concluding that the frontal lobes did not evolve especially fast along the human lineage after it split from the chimpanzee lineage.
(Source: eurekalert.org)
New subtype of ataxia identified
The finding opens the door for presymptomatic diagnostics and genetic counselling for patients and it is the first step in identifying the cause and developing therapies
(Image: Antony Gormley)
Researchers from the Germans Trias i Pujol Health Sciences Research Institute Foundation (IGTP), the Bellvitge Biomedical Research Institute (IDIBELL), and the Sant Joan de Déu de Martorell Hospital, has identified a new subtype of ataxia, a rare disease without treatment that causes atrophy in the cerebellum and affects around 1.5 million people in the world. The results have been published online on April 29 in the journal JAMA Neurology.
The cause of ataxia is a diverse genetic alteration. For this reason it is classified in subtypes. The new subtype identified described by the researchers has been called SCA37. The study has found this subtype in members of the same family living in Barcelona, Huelva and Madrid and Salamanca (Spain). The finding will allow in the medium term that these families and all who suffer the genetic alteration identified will have personalized therapies and diagnostics prior to the development of the disease. The study was funded by La Marató de TV3 (the Catalan public TV) in 2009, dedicated to rare diseases.
The cerebellum is a part of the brain located behind the brain that, among other functions, coordinates the movements of the human body. When it is atrophied, movement disorders appear, and when the ataxia evolves, the patients suffer frequent falls and swallowing problems. Progressively, they end up needing a wheelchair. Until now, there have been identified more than 30 different subtypes of ataxia, the first of which was described in 1993 by Dr. Antoni Matill, head of the Neurogenetics Unit, IGTP, and Dr. Victor Volpini, head of the Center for Molecular Genetic Diagnosis at IDIBELL.
The publication of this paper has been possible thanks to the collaboration of the Hospital de Sant Pau, Universitat Pompeu Fabra and the Pitie-Salpêtrière Hospital in Paris.
Particular eye movements
The first symptoms of ataxia may develop during the childhood or adult stage, depending on the subtype. The SCA37 subtype, the first cases of which were identified by Carme Serrano, neurologist at the Sant Joan de Deu Hospital, Martorell (Barcelona), is expressed at 48 years on average. One of the features of SCA37 subtype is the difficulty for vertical eye movements. Besides the patients identified in Spain by Dr. Serrano and Germans Trias and IDIBELL researchers, there are evidence of the existence of more people affected with this subtype of ataxia in France, Holland and Britain, and for this reason it seems to be a quite prevalent subtype of ataxia in Europe.
All SCA37 patients have a common genetic alteration in the portion 32 of the short arm of chromosome 1, wherein there are a hundred genes. Currently, researchers are sequencing it with new generation technologies to find the specific mutation that causes ataxia. When it is found it will be possible to make an accurate diagnosis in family members who do not yet have developed symptoms. Also, it will be possible to investigate the biological mechanisms that cause ataxia in order to develop and implement personalized therapies, with drugs or stem cells therapy.
(Source: eurekalert.org)
Brain Size Didn’t Drive Evolution, Research Suggests
Brain organization, not overall size, may be the key evolutionary difference between primate brains, and the key to what gives humans their smarts, new research suggests.
In the study, researchers looked at 17 species that span 40 million years of evolutionary time, finding changes in the relative size of specific brain regions, rather than changes in brain size, accounted for three-quarters of brain evolution over that time. The study, published today (March 26) in the Proceedings of the Royal Society B, also revealed that massive increases in the brain’s prefrontal cortex played a critical role in great ape evolution.
"For the first time, we can really identify what is so special about great ape brain organization," said study co-author Jeroen Smaers, an evolutionary biologist at the University College London.
Is bigger better?
Traditionally, scientists have thought humans’ superior intelligence derived mostly from the fact that our brains are three times bigger than our nearest living relatives, chimpanzees.
But bigger isn’t always better. Bigger brains take much more energy to power, so scientists have hypothesized that brain reorganization could be a smarter strategy to evolve mental abilities.
To see how brain organization evolved throughout primates, Smaers and his colleague Christophe Soligo analyzed post-mortem slices of brains from 17 different primates, then mapped changes in brain size onto an evolutionary tree.
Over evolutionary time, several key brain regions increased in size relative to other regions. Great apes (especially humans) saw a rise in white matter in the prefrontal cortex, which contributes to social cognition, moral judgments, introspection and goal-directed planning.
"The prefrontal cortex is a little bit like the CEO of the brain," Smaers told LiveScience. "It takes information from other brain areas and it synthesizes them."
When great apes diverged from old-world monkeys about 20 million years ago, brain regions tied to motor planning also increased in relative size. That could have helped them orchestrate the complex movements needed to manipulate tools — possibly to get at different food sources, Smaers said.
Gibbons and howler monkeys showed a different pattern. Even though their bodies and their brains got smaller over time, the hippocampus, which plays a role in spatial tasks, tended to increase in size in relation to the rest of the brain. That may have allowed these monkeys to be spatially adept and inhabit a more diverse range of environments.
Prefrontal cortex
The study shows that specific parts of the brain can selectively scale up to meet the demands of new environments, said Chet Sherwood, an anthropologist at George Washington University, who was not involved in the study.
The finding also drives home the importance of the prefrontal cortex, he said.
"It’s very suggestive that connectivity of prefrontal cortex has been a particularly strong driving force in ape and human brains," Sherwood told LiveScience.
Dysfunction in cerebellar Calcium channel causes motor disorders and epilepsy
One ion channel, many diseases
A dysfunction of a certain Calcium channel, the so called P/Q-type channel, in neurons of the cerebellum is sufficient to cause different motor diseases as well as a special type of epilepsy. This is reported by the research team of Dr. Melanie Mark and Prof. Dr. Stefan Herlitze from the Ruhr-Universität Bochum. They investigated mice that lacked the ion channel of the P/Q-type in the modulatory input neurons of the cerebellum. “We expect that our results will contribute to the development of treatments for in particular children and young adults suffering from absence epilepsy”, Melanie Mark says. The research team from the Department of General Zoology and Neurobiology reports in the “Journal of Neuroscience”.
P/Q-type channel defects cause a range of diseases
“One of the main challenging questions in neurobiology related to brain disease is in which neuronal circuit or cell-type the diseases originate,” Melanie Mark says. The Bochum researchers aimed at answering this question for certain motor disorders that are caused by cerebellar dysfunction. More specifically, they investigated potential causes of motor incoordination, also known as ataxia, and motor seizures, i.e., dyskinesia. In a previous study in 2011, the researchers showed that a certain Calcium channel type, called P/Q-type channel, in cerebellar neurons can be the origin of the diseases. The channel is expressed throughout the brain, and mutations in this channel cause migraines, different forms of epilepsy, dyskinesia, and ataxia in humans.
Disturbing cerebellar output is sufficient to cause different diseases
“Surprisingly, we found in 2011 that the loss of P/Q-type channels, specifically in the sole output pathway of the cerebellar cortex, the Purkinje cells, not only leads to ataxia and dyskinesia, but also to a disease often occurring in children and young adults, absence epilepsy,” Dr. Mark says. The research team thus hypothesized that disturbing the output signals of the cerebellum is sufficient to cause the major disease phenotypes associated with the P/Q-type channel. In other words, P/Q-type channel mutations in the cerebellum alone can elicit a range of diseases, even when the same channels in other brain regions are intact.
Disturbing the input to the cerebellum has similar effects as disturbing the output
Mark’s team has now found further evidence for this hypothesis. In the present study, the biologists did not disturb the output signals, i.e., the Purkinje cells, directly, but rather the input to these cells. The Purkinje cells are modulated by signals from other neurons, amongst others from the granule cells. “This modulatory input to the Purkinje cells is important for the proper communication between neurons in the cerebellum,” Melanie Mark explains. In mice, the researchers disturbed the input signals by genetically altering the granule cells so that they did not express the P/Q-type channel. Like disturbing the cerebellar output in the 2011 study, this manipulation resulted in ataxia, dyskinesia, and absence epilepsy. “The results provide additional evidence that the cerebellum is involved in initiating and/or propagating neurological deficits”, Mark sums up. “They also provide an animal model for identifying the specific pathways and molecules in the cerebellum responsible for causing these human diseases.”
(Source: alphagalileo.org)
BrainBow is a technique where cells are made to express several fluorescent proteins, in essentially random amounts. The randomness derives from feedback loops in gene expression. Mixing of fluorescence wavelengths yields a remarkable colour contrast on the single-neuron level.
The method was originally developed by Jeff W. Lichtman and Joshua R. Sanes at the Department of Neurobiology, Harvard Medical School.
Read more about BrainBow on Wikipedia or an introduction at the Harvard Gazette.