Neuroscience

Articles and news from the latest research reports.

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‘Back to sleep’ does not affect baby’s ability to roll UAlberta research shows little change in babies’ ability to roll from their tummy to back and vice versa 20 years after “back to sleep” campaign. Baby, keep on rolling. A campaign to put babies to bed on their backs to reduce the risk of sudden infant death syndrome has not impaired infants’ rolling abilities, according to University of Alberta research. Johanna Darrah, a professor of physical therapy in the Faculty of Rehabilitation Medicine, says infants develop the ability to roll much the same today as they did 20 years ago when the “back to sleep” campaign was introduced and successfully reduced the occurrence of SIDS. Her research answers fears that the back to sleep campaign, which recommends putting babies to bed on their back instead of their stomach, would hurt an infant’s gross motor development, specifically the ability to roll from tummy to back and vice versa. “Infant gross motor development hasn’t changed that much in 20 years,” says Darrah. “The thought that babies first roll from their tummy to their back, before they go from their back to their tummy, does not appear to be the case. For most babies, they happen very close together.” Darrah first studied infant motor development in the early 1990s as a graduate student of former dean Martha Cook Piper when the pair published the Alberta Infant Motor Scale, an observational assessment scale used throughout the world to measure infant motor skill development from birth to walking. More than 20 years later, Darrah revisited the work, studying the rolling abilities and motor skills development of 725 Canadian infants ranging in age from one week to eight months. One of her goals was to see whether the norms identified and developed 20 years ago still represent the age of emergence of gross motor skills. Darah notes there is some concern in the physical therapy community that babies develop movement skills like rolling from tummy to back at later ages because of reduced time spent on their stomachs. Those concerns appear to be unfounded, she says, explaining that her results are particularly valuable for health-care practitioners specializing in early childhood development. “Our results would suggest that gross motor skills emerge in the same order and at the same ages as 20 years ago. The environment is of course important to gross motor development, but the change in a sleeping position hasn’t made much difference as to when babies roll from stomach to back.”

‘Back to sleep’ does not affect baby’s ability to roll

UAlberta research shows little change in babies’ ability to roll from their tummy to back and vice versa 20 years after “back to sleep” campaign.

Baby, keep on rolling. A campaign to put babies to bed on their backs to reduce the risk of sudden infant death syndrome has not impaired infants’ rolling abilities, according to University of Alberta research.

Johanna Darrah, a professor of physical therapy in the Faculty of Rehabilitation Medicine, says infants develop the ability to roll much the same today as they did 20 years ago when the “back to sleep” campaign was introduced and successfully reduced the occurrence of SIDS. Her research answers fears that the back to sleep campaign, which recommends putting babies to bed on their back instead of their stomach, would hurt an infant’s gross motor development, specifically the ability to roll from tummy to back and vice versa.

“Infant gross motor development hasn’t changed that much in 20 years,” says Darrah. “The thought that babies first roll from their tummy to their back, before they go from their back to their tummy, does not appear to be the case. For most babies, they happen very close together.”

Darrah first studied infant motor development in the early 1990s as a graduate student of former dean Martha Cook Piper when the pair published the Alberta Infant Motor Scale, an observational assessment scale used throughout the world to measure infant motor skill development from birth to walking.

More than 20 years later, Darrah revisited the work, studying the rolling abilities and motor skills development of 725 Canadian infants ranging in age from one week to eight months. One of her goals was to see whether the norms identified and developed 20 years ago still represent the age of emergence of gross motor skills.

Darah notes there is some concern in the physical therapy community that babies develop movement skills like rolling from tummy to back at later ages because of reduced time spent on their stomachs. Those concerns appear to be unfounded, she says, explaining that her results are particularly valuable for health-care practitioners specializing in early childhood development.

“Our results would suggest that gross motor skills emerge in the same order and at the same ages as 20 years ago. The environment is of course important to gross motor development, but the change in a sleeping position hasn’t made much difference as to when babies roll from stomach to back.”

Filed under infants back to sleep campaign motor development sudden infant death syndrome science

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Researchers Identify Genetic Signature of Deadly Brain Cancer

A multi-institutional team of researchers have pinpointed the genetic traits of the cells that give rise to gliomas – the most common form of malignant brain cancer. The findings, which appear in the journal Cell Reports, provide scientists with rich new potential set of targets to treat the disease.

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“This study identifies a core set of genes and pathways that are dysregulated during both the early and late stages of tumor progression,” said University of Rochester Medical Center (URMC) neurologist Steven Goldman, M.D., Ph.D., the senior author of the study and co-director of the Center for Translational Neuromedicine. “By virtue of their marked difference from normal cells, these genes appear to comprise a promising set of targets for therapeutic intervention.”

As its name implies, gliomas arise from a cell type found in the central nervous system called the glial cell. Gliomas progress in severity over time and ultimately become highly invasive tumors known as glioblastomas, which are difficult to treat and almost invariably fatal. Current treatments, which include surgery, radiation therapy, and chemotherapy, can delay disease progression, but ultimately prove ineffective. 

Cancer research has been transformed over the past several years by new concepts arising from stem cell biology. Scientists now appreciate that many cancers are the result of rogue stem cells or their offspring, known as progenitor cells. Traditional cancer therapies often do not prevent a recurrence of the disease since they may not effectively target and destroy the cancer-causing stem cells that lie at the heart of the tumors.

Gliomas are one such example. The source of the cancer is a cell found in the brain called the glial progenitor cell. The cells, which arise from and maintain characteristics of stem cells, comprise about three percent of the cell population of the human brain. When these cells become cancerous they are transformed into glioma stem cells, essentially glial progenitor cells whose molecular machinery has gone awry, resulting in uncontrolled cell division.

Goldman and his team have long studied normal glial progenitor cells. These cells produce glia, a category that includes both astrocytes – cells that support the function of neurons – and oligodendrocytes – cells that produces myelin, the fatty insulation that allows the long-distance conduction of neural impulses.

While Goldman’s group’s work has primarily focused on ways to use glial progenitor cells to treat neurological disorders such as multiple sclerosis, their understanding of the biology of these cells and mastery of the techniques required to sort, identify, and isolate these cells has also enabled them to explore the molecular and genetic changes that transform these cells into cancers.

Using human tissue samples representing the three principal stages of the cancer, the researchers were able to identify and isolate the cancer-inducing stem cells. Working with Goldman, lead authors Romane Auvergne, Ph.D. and Fraser Sim, Ph.D. then compared the gene expression profiles of these cancer stem cells to those of normal glial progenitor cells. The objective was to both pinpoint the earliest genetic changes associated with cancer formation and identify those genes that were unique to the cancer stem cells and were expressed at every stage of disease progression.

Out of a pool over 44,000 tested genes and sequences, the scientists identified a small set of genes in the cancerous glioma progenitor cells that were over-expressed at all stages of malignancy. These genes formed a unique “signature” that identified the tumor progenitor cells and enabled the scientists to define a corresponding set of potential therapeutic targets present throughout all stages of the cancer.

“One of the key things you are looking for in drug development in cancer is a protein or gene that is over-expressed, so that you can attempt to achieve therapeutic benefit by inhibiting it,” said Goldman. 

The researchers chose to test this hypothesis by targeting one such gene, called SIX1, which was highly overexpressed in the glioma progenitor cells. While this particular gene is active in the early development of the nervous system, it had not been observed in the adult brain before. However, SIX1 signaling has been associated with breast and ovarian cancer, raising the possibility of its contribution to brain cancer as well. This turned out to indeed be the case. When the researchers blocked – or knocked down – the expression of this gene, the tumor cells ceased growing, and implanted tumors shrank. 

“This study gives us a blueprint to develop new therapies,” said Goldman. “We can now devise a strategy to systematically and rationally analyze – and eliminate – glioma stem and progenitor cells using compounds that may selectively target these cells, relative to the normal glial progenitors from which they derive. By targeting genes like SIX1 that are expressed at all stages of glioma progression, we hope to be able to effectively treat gliomas regardless of their stage of malignancy.  And by targeting the glioma-initiating cells in particular, we hope to lessen the likelihood of recurrence of these tumors, regardless of the stage at which we initiate treatment.”

(Source: urmc.rochester.edu)

Filed under glioblastomas brain cancer stem cells progenitor cells tumor progression science

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Technique Could Identify Patients at High Risk of Stroke or Brain Hemorrhage

Measuring blood flow in the brain may be an easy, noninvasive way to predict stroke or hemorrhage in children receiving cardiac or respiratory support through a machine called ECMO, according to a new study by researchers at Nationwide Children’s Hospital. Early detection would allow physicians to alter treatment and take steps to prevent these complications—the leading cause of death for patients on ECMO.

Short for extracorporeal membrane oxygenation, ECMO is used when a patient is unable to sustain enough oxygen in the blood supply due to heart failure, septic shock, or other life-threatening condition, said Nicole O’Brien, MD, a physician and scientist in critical care medicine at Nationwide Children’s and lead author of the study, which appears in a recent issue of the journal Pediatric Critical Care Medicine. The patient is connected to ECMO with tubes that carry the patient’s blood from a vein through the machine, where it is oxygenated and funneled back to the patient via an artery or vein that then distributes the oxygen-rich blood to vital organs and tissues.

The disease processes that lead someone to need ECMO are different, O’Brien noted, but it is used only after traditional therapies, such as a ventilator, fail. One of the biggest risks of ECMO is bleeding in the brain. Only 36 percent of children who suffer this complication survive, many left with permanent neurologic injury.

“Most of these patients are critically ill before they go on ECMO and often have low oxygen levels, low blood pressure and poor heart function, all of which can certainly lead to strokes,” said O’Brien, also an associate professor of clinical medicine at The Ohio State University College of Medicine. “Still, some patients develop problems and others don’t and we don’t understand why.”

To better understand the cause for these brain bleeds, O’Brien launched a pilot study to monitor cerebral blood flow using a transcranial doplar ultrasound machine, a portable, noninvasive technology that uses sound waves to measure the amount and speed of blood flowing through the brain. All patients on ECMO experience a change in cranial blood flow, but O’Brien wanted to see if those variations offered any hint as to why some patients had complications while others didn’t.

She measured cranial blood flow in 18 ECMO patients, taking the first reading within the patient’s first 24 hours on the machine, then again each day they received the treatment and one more time after ECMO therapy ended.

When she compared these measurements to normal cerebral blood flow rates for children in the same age group, she found significant differences. Thirteen of the children in the study developed no neurologic complications while on ECMO. In these children, cerebral blood flow was 40 percent to 50 percent lower than normal. But in the five patients who had either a stroke or brain hemorrhage while on ECMO, cerebral blood flow was 100 percent higher than normal.

The age of the child, length of time on ECMO or the underlying illness didn’t seem to matter. The only difference was that cerebral blood flow was dramatically increased in patients who ultimately had problems. While O’Brien found that interesting, the most intriguing finding was that the increase in blood flow occurred as long as two to six days before the patient began bleeding in the brain.

“That could give us a lot of lead time to prevent the brain bleeds or hemorrhages,” said O’Brien.

Physicians may decide to try to wean a patient off ECMO a little more quickly or change the dosage of anti-coagulant medication that all ECMO patients take.

Although O’Brien is excited about the results, she is careful to note that the findings are preliminary. She is planning a multi-center trial to see if the outcome will be the same in a larger study population.

“We still need to understand why these kids bleed and why they stroke,” said O’Brien. “This little piece of information is the very tip of the iceberg in terms of why that happens.”

(Source: nationwidechildrens.org)

Filed under brain hemorrhage blood flow extracorporeal membrane oxygenation stroke medicine science

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Blood Vessels in the Eye Linked With IQ, Cognitive Function The width of blood vessels in the retina, located at the back of the eye, may indicate brain health years before the onset of dementia and other deficits, according to a new study published in Psychological Science, a journal of the Association for Psychological Science. Research shows that younger people who score low on intelligence tests, such as IQ, tend to be at higher risk for poorer health and shorter lifespan, but factors like socioeconomic status and health behaviors don’t fully account for the relationship. Psychological scientist Idan Shalev of Duke University and colleagues wondered whether intelligence might serve as a marker indicating the health of the brain, and specifically the health of the system of blood vessels that provides oxygen and nutrients to the brain. To investigate the potential link between intelligence and brain health, the researchers borrowed a technology from a somewhat unexpected domain: ophthalmology. Shalev and colleagues used digital retinal imaging, a relatively new and noninvasive method, to gain a window onto vascular conditions in the brain by looking at the small blood vessels of the retina, located at the back of the eye. Retinal blood vessels share similar size, structure, and function with blood vessels in the brain and can provide a way of examining brain health in living humans. The researchers examined data from participants taking part in the Dunedin Multidisciplinary Health and Development Study, a longitudinal investigation of health and behavior in over 1000 people born between April 1972 and March 1973 in Dunedin, New Zealand. The results were intriguing. Having wider retinal venules was linked with lower IQ scores at age 38, even after the researchers accounted for various health, lifestyle, and environmental risk factors that might have played a role. Individuals who had wider retinal venules showed evidence of general cognitive deficits, with lower scores on numerous measures of neurospsychological functioning, including verbal comprehension, perceptual reasoning, working memory, and executive function. Surprisingly, the data revealed that people who had wider venules at age 38 also had lower IQ in childhood, a full 25 years earlier. It’s “remarkable that venular caliber in the eye is related, however modestly, to mental test scores of individuals in their 30s, and even to IQ scores in childhood,” the researchers observe. The findings suggest that the processes linking vascular health and cognitive functioning begin much earlier than previously assumed, years before the onset of dementia and other age-related declines in brain functioning. “Digital retinal imaging is a tool that is being used today mainly by eye doctors to study diseases of the eye,” Shalev notes. “But our initial findings indicate that it may be a useful investigative tool for psychological scientists who want to study the link between intelligence and health across the lifespan.” The current study doesn’t address the specific mechanisms that drive the relationship between retinal vessels and cognitive functioning, but the researchers surmise that it may have to do with oxygen supply to the brain. “Increasing knowledge about retinal vessels may enable scientists to develop better diagnosis and treatments to increase the levels of oxygen into the brain and by that, to prevent age-related worsening of cognitive abilities,” they conclude.

Blood Vessels in the Eye Linked With IQ, Cognitive Function

The width of blood vessels in the retina, located at the back of the eye, may indicate brain health years before the onset of dementia and other deficits, according to a new study published in Psychological Science, a journal of the Association for Psychological Science.

Research shows that younger people who score low on intelligence tests, such as IQ, tend to be at higher risk for poorer health and shorter lifespan, but factors like socioeconomic status and health behaviors don’t fully account for the relationship. Psychological scientist Idan Shalev of Duke University and colleagues wondered whether intelligence might serve as a marker indicating the health of the brain, and specifically the health of the system of blood vessels that provides oxygen and nutrients to the brain.

To investigate the potential link between intelligence and brain health, the researchers borrowed a technology from a somewhat unexpected domain: ophthalmology.

Shalev and colleagues used digital retinal imaging, a relatively new and noninvasive method, to gain a window onto vascular conditions in the brain by looking at the small blood vessels of the retina, located at the back of the eye. Retinal blood vessels share similar size, structure, and function with blood vessels in the brain and can provide a way of examining brain health in living humans.

The researchers examined data from participants taking part in the Dunedin Multidisciplinary Health and Development Study, a longitudinal investigation of health and behavior in over 1000 people born between April 1972 and March 1973 in Dunedin, New Zealand.

The results were intriguing.

Having wider retinal venules was linked with lower IQ scores at age 38, even after the researchers accounted for various health, lifestyle, and environmental risk factors that might have played a role.

Individuals who had wider retinal venules showed evidence of general cognitive deficits, with lower scores on numerous measures of neurospsychological functioning, including verbal comprehension, perceptual reasoning, working memory, and executive function.

Surprisingly, the data revealed that people who had wider venules at age 38 also had lower IQ in childhood, a full 25 years earlier.

It’s “remarkable that venular caliber in the eye is related, however modestly, to mental test scores of individuals in their 30s, and even to IQ scores in childhood,” the researchers observe.

The findings suggest that the processes linking vascular health and cognitive functioning begin much earlier than previously assumed, years before the onset of dementia and other age-related declines in brain functioning.

“Digital retinal imaging is a tool that is being used today mainly by eye doctors to study diseases of the eye,” Shalev notes. “But our initial findings indicate that it may be a useful investigative tool for psychological scientists who want to study the link between intelligence and health across the lifespan.”

The current study doesn’t address the specific mechanisms that drive the relationship between retinal vessels and cognitive functioning, but the researchers surmise that it may have to do with oxygen supply to the brain.

“Increasing knowledge about retinal vessels may enable scientists to develop better diagnosis and treatments to increase the levels of oxygen into the brain and by that, to prevent age-related worsening of cognitive abilities,” they conclude.

Filed under blood vessels retinal blood vessels cognitive deficit IQ intelligence brain psychology neuroscience science

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Positive Feedback: Researchers have found a new role for mTOR in autism-related disorders Researchers have found a novel role for a protein that has been implicated in an autism-related disorder known as tuberous sclerosis complex (TSC). The disease, which affects 1 in about 8,000 children, manifests itself in the form of mental retardation in addition to severe epileptic episodes. The disease is caused by mutations in two tumor-suppressing proteins, TSC1 and TSC2. “Kids with this condition have benign tumors that grow all over the body,” said Bernardo Sabatini, the Takeda Professor of Neurobiology at Harvard Medical School and senior author of the study, “but we wanted to know what happened in the brain.” The researchers found that when mutations in TSC1 and TSC2 adversely affected a third protein, mTOR, this mutation increased brain activity, which can result in epileptic seizures. The findings were published in the May 8 issue of Neuron. A protein kinase, mTOR is responsible for controlling cell growth in many parts of the body and has been widely implicated in epilepsy and autism. TSC1 and TSC2 normally repress the activity of mTOR to keep cell growth in check. In the case of TSC, there are mutations in TSC1 or TSC2, and mTOR’s ability to promote cell growth goes unchecked, resulting in tumors in regularly dividing cells. “But neurons don’t divide,” said Sabatini. “So it was important to note the changes in these non-dividing cells.”   The researchers hypothesized that mTOR’s function in the brain related to homeostasis, the brain’s ability to maintain a controlled level of electrical activity. When there’s a lot of electrical activity, a negative feedback system switches on to suppress activity. Conversely, when levels are too low, other positive feedback pathways are engaged that bring the activity level back up. “We went into this study with the specific hypothesis that mTOR would be part of the homeostatic loop in the brain,” explained Sabatini.   In the case of TSC patients, they thought that mTOR was incapable of maintaining homeostasis and kept adding to the level of electrical activity, leading to seizures.  “But we were wrong,” he added. “What we actually found was that mTOR is part of a positive feedback pathway,” said Helen Bateup, HMS research fellow in neurobiology and first author on the study. “When a cell is active, mTOR gets turned on more frequently and makes the cell even more active by reducing the amount of inhibition that the neuron receives.” In cells where TSC proteins are mutated, this positive feedback gets out of control, and the neuronal circuit remains overactive despite all the pathways that normally shut down activity being turned on. “It’s like the circuit is trying to keep itself quiet, but it can’t,” said Sabatini. “The out-of-control mTOR causes some cells to loss all inhibition, something that can’t be compensated for by turning down excitation.”                                         The researchers think this key difference in how mTOR operates, in working to promote electrical activity, is important for the disease because patients end up with high levels of dysfunctional mTOR that makes for highly active circuits prone to epileptic fits. Furthermore, “we know that once a person has one seizure, they’re much more likely to have more, a concept known as kindling,” said Sabatini. These findings are among the first to show that contrary to scientific consensus, mTOR does not play a part in everything. “We have shown that one of the few things that mTOR does not seem to partake in is this negative feedback pathway,” said Sabatini. Working in both in vitro and in vivo mouse models, the researchers think the next step would be tease out the molecular pathway of mTOR’s involvement in this positive feedback loop. “It’s also important to compare how this pathway works in normal brains versus a diseased model,” added Bateup. “A huge challenge when studying the brain is that there are so many feedback pathways that a mutation in one gene can result in a hundred other secondary changes,” said Sabatini. Rapamycin, a drug currently used to prevent organ rejection following transplants, targets mTOR and brings activity levels back to normal. “We could use the drug to restore this excitatory-inhibitory balance in the brain,” said Bateup. “A lot of drugs that treat epilepsy try to make inhibition more powerful but given that the primary problem here is that a group of cells has lost inhibition, that approach won’t work,” she added. “What we might need is to target the excitation side. Or find ways of changing the biochemistry of the cells to make inhibitory synapses again.”  “For this disease, this is the right time to start looking at human cells,” said Sabatini. “We have really good data from the mouse model and it would be a really nice test to see if the mouse model is really predictive of human disorder and if it’s worth being continued.” 

Positive Feedback: Researchers have found a new role for mTOR in autism-related disorders

Researchers have found a novel role for a protein that has been implicated in an autism-related disorder known as tuberous sclerosis complex (TSC).

The disease, which affects 1 in about 8,000 children, manifests itself in the form of mental retardation in addition to severe epileptic episodes. The disease is caused by mutations in two tumor-suppressing proteins, TSC1 and TSC2.

“Kids with this condition have benign tumors that grow all over the body,” said Bernardo Sabatini, the Takeda Professor of Neurobiology at Harvard Medical School and senior author of the study, “but we wanted to know what happened in the brain.”

The researchers found that when mutations in TSC1 and TSC2 adversely affected a third protein, mTOR, this mutation increased brain activity, which can result in epileptic seizures.

The findings were published in the May 8 issue of Neuron.

A protein kinase, mTOR is responsible for controlling cell growth in many parts of the body and has been widely implicated in epilepsy and autism. TSC1 and TSC2 normally repress the activity of mTOR to keep cell growth in check. In the case of TSC, there are mutations in TSC1 or TSC2, and mTOR’s ability to promote cell growth goes unchecked, resulting in tumors in regularly dividing cells.

“But neurons don’t divide,” said Sabatini. “So it was important to note the changes in these non-dividing cells.”  

The researchers hypothesized that mTOR’s function in the brain related to homeostasis, the brain’s ability to maintain a controlled level of electrical activity. When there’s a lot of electrical activity, a negative feedback system switches on to suppress activity. Conversely, when levels are too low, other positive feedback pathways are engaged that bring the activity level back up.

“We went into this study with the specific hypothesis that mTOR would be part of the homeostatic loop in the brain,” explained Sabatini.  

In the case of TSC patients, they thought that mTOR was incapable of maintaining homeostasis and kept adding to the level of electrical activity, leading to seizures. 

“But we were wrong,” he added.

“What we actually found was that mTOR is part of a positive feedback pathway,” said Helen Bateup, HMS research fellow in neurobiology and first author on the study. “When a cell is active, mTOR gets turned on more frequently and makes the cell even more active by reducing the amount of inhibition that the neuron receives.”

In cells where TSC proteins are mutated, this positive feedback gets out of control, and the neuronal circuit remains overactive despite all the pathways that normally shut down activity being turned on.

“It’s like the circuit is trying to keep itself quiet, but it can’t,” said Sabatini. “The out-of-control mTOR causes some cells to loss all inhibition, something that can’t be compensated for by turning down excitation.”                                        

The researchers think this key difference in how mTOR operates, in working to promote electrical activity, is important for the disease because patients end up with high levels of dysfunctional mTOR that makes for highly active circuits prone to epileptic fits. Furthermore, “we know that once a person has one seizure, they’re much more likely to have more, a concept known as kindling,” said Sabatini.

These findings are among the first to show that contrary to scientific consensus, mTOR does not play a part in everything.

“We have shown that one of the few things that mTOR does not seem to partake in is this negative feedback pathway,” said Sabatini.

Working in both in vitro and in vivo mouse models, the researchers think the next step would be tease out the molecular pathway of mTOR’s involvement in this positive feedback loop. “It’s also important to compare how this pathway works in normal brains versus a diseased model,” added Bateup.

“A huge challenge when studying the brain is that there are so many feedback pathways that a mutation in one gene can result in a hundred other secondary changes,” said Sabatini.

Rapamycin, a drug currently used to prevent organ rejection following transplants, targets mTOR and brings activity levels back to normal.

“We could use the drug to restore this excitatory-inhibitory balance in the brain,” said Bateup. “A lot of drugs that treat epilepsy try to make inhibition more powerful but given that the primary problem here is that a group of cells has lost inhibition, that approach won’t work,” she added. “What we might need is to target the excitation side. Or find ways of changing the biochemistry of the cells to make inhibitory synapses again.” 

“For this disease, this is the right time to start looking at human cells,” said Sabatini. “We have really good data from the mouse model and it would be a really nice test to see if the mouse model is really predictive of human disorder and if it’s worth being continued.” 

Filed under brain activity tuberous sclerosis complex neurons mutations autism neuroscience science

98 notes

Manipulating Memory in the Hippocampus

Protein modification may help control Alzheimer’s and epilepsy, TAU researchers find

In the brain, cell-to-cell communication is dependent on neurotransmitters, chemicals that aid the transfer of information between neurons. Several proteins have the ability to modify the production of these chemicals by either increasing or decreasing their amount, or promoting or preventing their secretion. One example is tomosyn, which hinders the secretion of neurotransmitters in abnormal amounts.

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Dr. Boaz Barak of Tel Aviv University’s Sagol School of Neuroscience, in collaboration with Prof. Uri Ashery, used a method for modifying the levels of this protein in the mouse hippocampus — the region of the brain associated with learning and memory. It had a significant impact on the brain’s activity: Over-production of the protein led to a sharp decline in the ability to learn and memorize information, the researchers reported in the journal NeuroMolecular Medicine.

"This study demonstrates that it is possible to manipulate various processes and neural circuits in the brain," says Dr. Barak, a finding which may aid in the development of therapeutic procedures for epilepsy and neurodegenerative diseases such as Alzheimer’s. Slowing the transmission rate of information when the brain is overactive during epileptic seizures could have a beneficial effect, and readjusting the levels of tomosyn in an Alzheimer’s patient may help increase cognition and combat memory loss.

A maze of memory loss

The researchers teamed up with a laboratory at the National Institutes of Health (NIH) in Baltimore to create a virus which produces the tomosyn protein. In the lab, the virus was injected into the hippocampus region in mice. Then, in order to test the consequences, they performed a series of behavioral tests designed to measure functions like memory, cognitive ability, and motor skills.

In one experiment, called the Morris Water Maze, mice had to learn to navigate to, and remember, the location of a hidden platform placed inside a pool with opaque water. During the first five days of testing, researchers found that the test group with an over-production of tomosyn had a significant problem in learning and memorizing the location of the platform, compared to a control group that received a placebo injection. And when the platform was removed from the maze, the test group spent less time swimming around the area where the platform once was, indicating that they had no memory of its existence. In comparison, the control group of mice searched for the missing platform in its previous location for two or even three days after its removal, notes Dr. Barak.

These findings were further verified by measuring electrical activity in the brains of both the test group and the control group. In the test group, researchers found decreased levels of transmissions between neurons in the hippocampus, a physiological finding that may explain the results of the behavioral tests.

Correcting neuronal processes

In the future, Dr. Barak believes that the ability to modify proteins directly in the brain will allow for more control over brain activities and the correction of neurodegenerative processes, such as providing stricter regulation in neuronal activity for epileptic patients or stimulating neurotransmitters to help with learning and memory loss in Alzheimer’s patients. Indeed, a separate study conducted by the researchers demonstrates that mouse models for Alzheimer’s disease do have an over-production of tomosyn in the hippocampus region, so countering the production of this protein could have a beneficial effect.

Now Dr. Barak and Prof. Ashery are working towards a method for artificially decreasing levels of the protein, which they believe will have the opposite effect on the cognitive ability of the mice. “We hypothesize that with an under-production in tomosyn, the mice will show a marked improvement in their performance in behavioral testing,” he says.

(Source: aftau.org)

Filed under neurodegenerative diseases epileptic seizures hippocampus cell communication memory neuroscience science

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Researchers focus on a brain protein and an antibiotic to block cocaine craving A new study conducted by a team of Indiana University neuroscientists demonstrates that GLT1, a protein that clears glutamate from the brain, plays a critical role in the craving for cocaine that develops after only several days of cocaine use. The study, appearing in The Journal of Neuroscience, showed that when rats taking large doses of cocaine are withdrawn from the drug, the production of GLT1 in the nucleus accumbens, a region of the brain implicated in motivation, begins to decrease. But if the rats receive ceftriaxone, an antibiotic used to treat meningitis, GLT1 production increases during the withdrawal period and decreases cocaine craving. George Rebec, professor in the Department of Psychological and Brain Sciences, said drug craving depends on the release of glutamate, a neurotransmitter involved in motivated behavior. Glutamate is released in response to the cues associated with drug taking, so when addicts are exposed to these cues, their drug craving increases even if they have been away from the drug for some time. The same behavior can be modeled in rats. When rats, who self-administer cocaine by pressing a lever that delivers the cocaine into their bodies, are withdrawn from the drug for several weeks, their craving returns if they are exposed to the cues that accompanied drug delivery in the past; in this case, a tone and light. But if the rats are treated with ceftriaxone during withdrawal, they no longer seek cocaine when the cues are presented. Ceftriaxone appears to block craving by reversing the decrease in GLT1 caused by repeated exposure to cocaine. In fact, ceftriaxone increases GLT1, which allows glutamate to be cleared quickly from the brain. The Rebec research group localized this effect to the nucleus accumbens by showing that if GLT1 was blocked in this brain region even after ceftriaxone treatment, the rats would relapse. While an earlier paper of Rebec’s group showed the effects of ceftriaxone on cocaine craving, the new paper was the first to localize the effects of ceftriaxone to the nucleus accumbens and was the first to show that ceftriaxone works after long withdrawal periods. "The idea is that increasing GLT1 will prevent relapse. If we block GLT1, the ceftriaxone should not work," Rebec said. "We now have good evidence that ceftriaxone is acting on GLT1 and that the nucleus accumbens is the critical site." Rebec said prior work on Huntington’s disease, a neurodegenerative disorder, alerted him and his team to the way ceftriaxone acts on the expression of GLT1, a protein that removes glutamate from the brain. Glutamate removal is a problem in Huntington’s disease, and Rebec’s team found that ceftriaxone increases GLT1 and improves neurological signs of the disease in mouse models. It now is important to determine why cocaine decreases GLT1 and to see whether other drugs of abuse have the same effect. Rebec and colleagues have shown that ceftriaxone also can decrease the craving for alcohol in rats selectively bred to prefer alcohol. Drug cues are one factor that can trigger relapse. Future work also will examine whether ceftriaxone can block drug craving induced by stress or by re-exposure to the drug. If so, it would mean that GLT1 could become an important target in the search for treatments to prevent drug relapse. Now, Rebec said, there are a number of factors to study. “We don’t yet know how long the effects of ceftriaxone last. Does an addict have to be on it for a month or will it lose its effectiveness? We don’t yet know what will happen.” In the cocaine study, the rats self-administer cocaine for six hours a day for up to 11 days. Their behavior is much like that of a human addict. "You might think that because they’re in there, they just take more, but they don’t just take more," Rebec said. "Like human addicts, they take the drug more and more rapidly and they want to get to it more and more quickly." Withdrawal serves as an incubation period during which craving increases if it is activated by cues or other factors. “Something changes in the brain during that time to trigger the craving or make it more likely that you want the drug,” Rebec said. “That’s what ceftriaxone seems to be interfering with.” Ceftriaxone is now in clinical trials on people with ALS, also known as Lou Gehrig’s disease, which has many mechanisms in common with other neurodegenerative diseases such as Huntington’s disease and Alzheimer’s.

Researchers focus on a brain protein and an antibiotic to block cocaine craving

A new study conducted by a team of Indiana University neuroscientists demonstrates that GLT1, a protein that clears glutamate from the brain, plays a critical role in the craving for cocaine that develops after only several days of cocaine use.

The study, appearing in The Journal of Neuroscience, showed that when rats taking large doses of cocaine are withdrawn from the drug, the production of GLT1 in the nucleus accumbens, a region of the brain implicated in motivation, begins to decrease. But if the rats receive ceftriaxone, an antibiotic used to treat meningitis, GLT1 production increases during the withdrawal period and decreases cocaine craving.

George Rebec, professor in the Department of Psychological and Brain Sciences, said drug craving depends on the release of glutamate, a neurotransmitter involved in motivated behavior. Glutamate is released in response to the cues associated with drug taking, so when addicts are exposed to these cues, their drug craving increases even if they have been away from the drug for some time.

The same behavior can be modeled in rats. When rats, who self-administer cocaine by pressing a lever that delivers the cocaine into their bodies, are withdrawn from the drug for several weeks, their craving returns if they are exposed to the cues that accompanied drug delivery in the past; in this case, a tone and light. But if the rats are treated with ceftriaxone during withdrawal, they no longer seek cocaine when the cues are presented.

Ceftriaxone appears to block craving by reversing the decrease in GLT1 caused by repeated exposure to cocaine. In fact, ceftriaxone increases GLT1, which allows glutamate to be cleared quickly from the brain. The Rebec research group localized this effect to the nucleus accumbens by showing that if GLT1 was blocked in this brain region even after ceftriaxone treatment, the rats would relapse.

While an earlier paper of Rebec’s group showed the effects of ceftriaxone on cocaine craving, the new paper was the first to localize the effects of ceftriaxone to the nucleus accumbens and was the first to show that ceftriaxone works after long withdrawal periods.

"The idea is that increasing GLT1 will prevent relapse. If we block GLT1, the ceftriaxone should not work," Rebec said. "We now have good evidence that ceftriaxone is acting on GLT1 and that the nucleus accumbens is the critical site."

Rebec said prior work on Huntington’s disease, a neurodegenerative disorder, alerted him and his team to the way ceftriaxone acts on the expression of GLT1, a protein that removes glutamate from the brain. Glutamate removal is a problem in Huntington’s disease, and Rebec’s team found that ceftriaxone increases GLT1 and improves neurological signs of the disease in mouse models.

It now is important to determine why cocaine decreases GLT1 and to see whether other drugs of abuse have the same effect. Rebec and colleagues have shown that ceftriaxone also can decrease the craving for alcohol in rats selectively bred to prefer alcohol.

Drug cues are one factor that can trigger relapse. Future work also will examine whether ceftriaxone can block drug craving induced by stress or by re-exposure to the drug. If so, it would mean that GLT1 could become an important target in the search for treatments to prevent drug relapse. Now, Rebec said, there are a number of factors to study. “We don’t yet know how long the effects of ceftriaxone last. Does an addict have to be on it for a month or will it lose its effectiveness? We don’t yet know what will happen.”

In the cocaine study, the rats self-administer cocaine for six hours a day for up to 11 days. Their behavior is much like that of a human addict.

"You might think that because they’re in there, they just take more, but they don’t just take more," Rebec said. "Like human addicts, they take the drug more and more rapidly and they want to get to it more and more quickly."

Withdrawal serves as an incubation period during which craving increases if it is activated by cues or other factors. “Something changes in the brain during that time to trigger the craving or make it more likely that you want the drug,” Rebec said. “That’s what ceftriaxone seems to be interfering with.”

Ceftriaxone is now in clinical trials on people with ALS, also known as Lou Gehrig’s disease, which has many mechanisms in common with other neurodegenerative diseases such as Huntington’s disease and Alzheimer’s.

Filed under cocaine cocaine use nucleus accumbens glutamate ceftriaxone animal model neuroscience science

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Brain Visualization Prototype Holds Promise for Precision Medicine The ability to combine all of a patient’s neurological test results into one detailed, interactive “brain map” could help doctors diagnose and tailor treatment for a range of neurological disorders, from autism to epilepsy. But before this can happen, researchers need a suite of automated tools and techniques to manage and make sense of these massive complex datasets. To get an idea of what these tools would look like, computational researchers from the Lawrence Berkeley National Laboratory (Berkeley Lab) are working with neuroscientists from the University of California, San Francisco (UCSF). So far, the Berkeley Lab team has used existing computational tools to translate UCSF laboratory data into 3D visualizations of brain structures and activity. Earlier this year, Los Angeles-based Oblong Industries joined the collaboration and implemented a state-of-the-art, gesture-based navigation interface that allows researchers to interactively explore 3D brain visualizations with hand poses movements. Researchers from Berkeley Lab, UCSF and Oblong Industries presented a  prototype of their brain simulation and innovative navigation interface at UCSF’s OME Precision Medicine Summit on Thursday, May 2. “The collaboration with Oblong will make our visualizations much more powerful and relevant to precision medicine,” says Daniela Ushizima, a Berkeley Lab computational researcher who is one of the collaboration’s principal investigators. “This collaboration gives us the opportunity to have tools to browse big data sets at our fingertips, literally.” Designed to generate actionable projects and collaborations, the OME Precision Medicine Summit brought together leaders in health, bioscience, technology, government and other fields to lay out a roadmap and remove barriers for the evolving field known as precision medicine. The field of precision medicine will allow future doctors to cross-reference an individual’s personal history and biology with patterns found worldwide and use that network of knowledge to pinpoint and deliver care that’s preventive, targeted, timely and effective.The Future: Tackling Neuroimaging’s Big Data Problem According to Ushizima, the brain visualization prototype provides just a small glimpse of what the collaboration hopes to achieve. Ultimately, they would like to incorporate chemical elements captured by Positron Emission Tomography (PET) scans, electrical brain activity captured by Functional Magnetic Resonance Imaging (fMRI) and anatomical structure as captured by T1, T2 and other MRI scans. As the collaboration continues, scientists in Berkeley Lab’s Visualization and Analytics Group hope to develop tools and techniques for imaging processing and analysis. This team will also develop methods for visualizing and comparing different modalities of brain data, for instance, figuring out how to compare an anatomical brain region (like the frontal cortex) with correlating chemical activity. Meanwhile, researchers in the Berkeley Lab’s Future Technologies, Scientific Computing and Complex Systems groups will use graph analytics and image analysis algorithms to quantify and visualize this “multi-modal” data, giving researchers the flexibility to look at regions of interest by displaying electrical, anatomical and chemical activity. By representing brain data on dynamical graphs, neuroscientists will be able to see how different parts of the brain correlate with each other. They will also be able to identify and track temporal changes, or changes over time. “The technologies that exist for imaging the brain are very advanced and diverse. We have machines that provide extremely high-throughput, high-definition images of the brain in 3D, but unfortunately the tools to analyze this information have not advanced as quickly,” says Ushizima. She notes that a relatively small amount of data collected from these imaging machines requires some level of manual curation, a process that can take anywhere from six months to a year. By automating and parallelizing this process, Ushizima believes this collaboration could change the paradigm.

Brain Visualization Prototype Holds Promise for Precision Medicine

The ability to combine all of a patient’s neurological test results into one detailed, interactive “brain map” could help doctors diagnose and tailor treatment for a range of neurological disorders, from autism to epilepsy. But before this can happen, researchers need a suite of automated tools and techniques to manage and make sense of these massive complex datasets.

To get an idea of what these tools would look like, computational researchers from the Lawrence Berkeley National Laboratory (Berkeley Lab) are working with neuroscientists from the University of California, San Francisco (UCSF). So far, the Berkeley Lab team has used existing computational tools to translate UCSF laboratory data into 3D visualizations of brain structures and activity. Earlier this year, Los Angeles-based Oblong Industries joined the collaboration and implemented a state-of-the-art, gesture-based navigation interface that allows researchers to interactively explore 3D brain visualizations with hand poses movements.

Researchers from Berkeley Lab, UCSF and Oblong Industries presented a  prototype of their brain simulation and innovative navigation interface at UCSF’s OME Precision Medicine Summit on Thursday, May 2.

“The collaboration with Oblong will make our visualizations much more powerful and relevant to precision medicine,” says Daniela Ushizima, a Berkeley Lab computational researcher who is one of the collaboration’s principal investigators. “This collaboration gives us the opportunity to have tools to browse big data sets at our fingertips, literally.”

Designed to generate actionable projects and collaborations, the OME Precision Medicine Summit brought together leaders in health, bioscience, technology, government and other fields to lay out a roadmap and remove barriers for the evolving field known as precision medicine. The field of precision medicine will allow future doctors to cross-reference an individual’s personal history and biology with patterns found worldwide and use that network of knowledge to pinpoint and deliver care that’s preventive, targeted, timely and effective.
The Future: Tackling Neuroimaging’s Big Data Problem

According to Ushizima, the brain visualization prototype provides just a small glimpse of what the collaboration hopes to achieve. Ultimately, they would like to incorporate chemical elements captured by Positron Emission Tomography (PET) scans, electrical brain activity captured by Functional Magnetic Resonance Imaging (fMRI) and anatomical structure as captured by T1, T2 and other MRI scans.

As the collaboration continues, scientists in Berkeley Lab’s Visualization and Analytics Group hope to develop tools and techniques for imaging processing and analysis. This team will also develop methods for visualizing and comparing different modalities of brain data, for instance, figuring out how to compare an anatomical brain region (like the frontal cortex) with correlating chemical activity.

Meanwhile, researchers in the Berkeley Lab’s Future Technologies, Scientific Computing and Complex Systems groups will use graph analytics and image analysis algorithms to quantify and visualize this “multi-modal” data, giving researchers the flexibility to look at regions of interest by displaying electrical, anatomical and chemical activity. By representing brain data on dynamical graphs, neuroscientists will be able to see how different parts of the brain correlate with each other. They will also be able to identify and track temporal changes, or changes over time.

“The technologies that exist for imaging the brain are very advanced and diverse. We have machines that provide extremely high-throughput, high-definition images of the brain in 3D, but unfortunately the tools to analyze this information have not advanced as quickly,” says Ushizima.

She notes that a relatively small amount of data collected from these imaging machines requires some level of manual curation, a process that can take anywhere from six months to a year. By automating and parallelizing this process, Ushizima believes this collaboration could change the paradigm.

Filed under 3D visualizations brain activity OME Precision Medicine Summit brain neuroscience science

244 notes

Is the Brain No Different From a Light Switch? The Uncomfortable Ideas of the Philosopher Daniel Dennett To a philosopher, is the human brain no different from a nonliving gizmo like a computer or a light switch? Is consciousness largely an illusion? Jonathan Weiner on the uncomfortable ideas of the thinker Daniel Dennett. For Daniel Dennett, philosophers are like blacksmiths: they make their own tools as they go along. Unlike carpenters, who have to buy their drills and saws at Sears, blacksmiths can use their own hammers, tongs, and anvils to pound out more hammers, tongs, and anvils. Dennett, whose famous white beard gives him the look of both a blacksmith and a philosopher, has been particularly industrious at the anvil. He has been working as a philosopher for 50 years, and in his new book, Intuition Pumps and Other Tools for Thinking, he shares a few tricks to make the hard work easier. He is a master at inventing tools for thought—metaphysical jokes, fables, parables, puzzles, and zany Monty-Python-like sketches that can help thinkers feel their way forward. Dennett calls them hand tools and power tools for the mind, and he’s built dozens and dozens of them over the years. “Thinking is hard,” he writes. “Thinking about some problems is so hard that it can make your head ache just thinking about thinking about them.” Thinking tools help philosophers work on the really deep, hard questions about life, the universe, and everything. They facilitate what another philosopher has called Jootsing, which stands for Jumping Out Of the System—the goal is to pop out of the goldfish bowl of commonplace ideas without drowning in thin air. Think of Plato’s Cave, for instance. That little story has helped philosophers puzzle about the nature of reality for more than 23 centuries and counting. Dennett’s own inventions include “Swampman Meets a Cow-Shark,” “Zombies and Zimboes,” and many other thought experiments that illuminate great questions in philosophy. He focuses on problems of free will, evolution, and consciousness. His ideas about consciousness are rather shocking; he can make you feel that the human brain itself is just a collection of tongs, hammers, and intuition pumps. (More about that in a moment.) Dennett has written more than a dozen books about those deep topics. His best known are Darwin’s Dangerous Idea, and Consciousness Explained. He writes very well, in a colorful, lively, clear style, and he is a popular professor at Tufts University, to which he dedicates his new book. And every book and lecture is packed with intuition pumps for juicy, jootsy epiphanies. In a way, we all use thinking tools, all the time, without thinking twice about them. Everyday speech is full of what Dennett calls “small hand tools,” familiar words and phrases like “wild goose chase” or “feedback” or “slam dunk.” The English language is a tool chest with a million metaphors that serve as a kind of verbal mathematics. They’re informal formulas for describing the way things go. Newton’s equations describe the behavior of a cannonball; “loose cannon” describes the behavior of a certain kind of cannoneer we’ve all had the misfortune to know. Then there are simple, familiar intuition pumps like Aesop’s “The Boy Who Cried Wolf,” “The Ant and the Grasshopper,” and “The Fox and the Grapes.” We’ve all used those thinking tools too. “Look how much you can say about what somebody has just said by asking, simply, ‘Sour grapes?’” writes Dennett. You can get someone to rethink her position, to consider her situation from a completely different perspective. You can also insult her. (As Dennett observes, “Tools can be used as weapons too.”) The intuition pumps that he’s created are really philosophical arguments in disguise. Dennett has designed them to push us to see the world his way, and that’s what he’s trying to do by recapitulating them here. “I will not just describe them,” he writes; “I intend to use them to move your mind gently through uncomfortable territory all the way to a quite radical vision of meaning, mind, and free will.” And his ideas are uncomfortable. His essential claim is that there is no great gulf between nonliving, unconscious gizmos like computers and light switches, on the one hand, and the human brain, on the other. Our strong feeling that there’s something special and inexplicable about consciousness is largely an illusion. It will fade as science advances, like the illusion that the Earth is the center of the universe and everything revolves around us. Biologists used to believe that living things are made of some special material, some elan vital that sets us apart from the stuff of rocks and minerals. Now that we know about DNA, we no longer need an elan vital. Someday we won’t need consciousness either. There’s no metaphysical difference between your body and your mind, or between your laptop and your necktop, so to speak. That’s a controversial position, obviously. It still feels counterintuitive to most of us, and to most philosophers too, in spite of all of Dennett’s intuition pumps. Does Consciousness Explained explain consciousness, or just explain it away? Check out Dennett’s story “The Sad Case of Mr. Clapgras” and see what you intuit. Mr. Clapgras wakes up one morning and finds that everything he sees is suddenly disgusting. His vision is still normal, but his associations with every color have somehow gone awry overnight. He now hates his old favorite color, red, and prefers his former least favorite, blue. Everything looks the same but nothing feels right. His food looks revolting—he has to eat in the dark. Dennett exploits the tale of poor Mr. Clapgras to raise difficult questions about the nature of perception, and thought, and to disrupt our faith in consciousness itself. Even if you don’t love logic puzzles, brainteasers, and code-writing, all of which delight Dennett, you may still find this book an entertaining introduction to Dennett’s tenets. As you stretch your mind on his mind-twisters, you begin to feel your way to glimpses of his view of life. At the same time, it’s also something like torture to twist your thoughts into the pretzel-shaped path that Dennett wants you to follow—to walk the Mobius-shaped ribbon of highway on which, no matter how you hurry and scurry ahead, you can never arrive at a place where there is something special about the human mind. Read this book carefully and you’ll find yourself Jumping Out of the System in all directions. Dennett will lift off the top of your head, and tie your forehead into knots. Is this really where the philosophy of mind is headed? There’s no question that as neuroscience hurtles ahead, our current system of thought is beginning to feel creaky and rusty in the extreme. Some bright new ideas probably are going to have to take its place. It may be that Dennett and his friends are the philosophers who are building them—Dennett most cheerfully of all, in his Santa’s workshop of intuition pumps.

Is the Brain No Different From a Light Switch? The Uncomfortable Ideas of the Philosopher Daniel Dennett

To a philosopher, is the human brain no different from a nonliving gizmo like a computer or a light switch? Is consciousness largely an illusion? Jonathan Weiner on the uncomfortable ideas of the thinker Daniel Dennett.

For Daniel Dennett, philosophers are like blacksmiths: they make their own tools as they go along. Unlike carpenters, who have to buy their drills and saws at Sears, blacksmiths can use their own hammers, tongs, and anvils to pound out more hammers, tongs, and anvils. Dennett, whose famous white beard gives him the look of both a blacksmith and a philosopher, has been particularly industrious at the anvil. He has been working as a philosopher for 50 years, and in his new book, Intuition Pumps and Other Tools for Thinking, he shares a few tricks to make the hard work easier. He is a master at inventing tools for thought—metaphysical jokes, fables, parables, puzzles, and zany Monty-Python-like sketches that can help thinkers feel their way forward. Dennett calls them hand tools and power tools for the mind, and he’s built dozens and dozens of them over the years.

“Thinking is hard,” he writes. “Thinking about some problems is so hard that it can make your head ache just thinking about thinking about them.” Thinking tools help philosophers work on the really deep, hard questions about life, the universe, and everything. They facilitate what another philosopher has called Jootsing, which stands for Jumping Out Of the System—the goal is to pop out of the goldfish bowl of commonplace ideas without drowning in thin air. Think of Plato’s Cave, for instance. That little story has helped philosophers puzzle about the nature of reality for more than 23 centuries and counting.

Dennett’s own inventions include “Swampman Meets a Cow-Shark,” “Zombies and Zimboes,” and many other thought experiments that illuminate great questions in philosophy. He focuses on problems of free will, evolution, and consciousness. His ideas about consciousness are rather shocking; he can make you feel that the human brain itself is just a collection of tongs, hammers, and intuition pumps. (More about that in a moment.) Dennett has written more than a dozen books about those deep topics. His best known are Darwin’s Dangerous Idea, and Consciousness Explained. He writes very well, in a colorful, lively, clear style, and he is a popular professor at Tufts University, to which he dedicates his new book. And every book and lecture is packed with intuition pumps for juicy, jootsy epiphanies.

In a way, we all use thinking tools, all the time, without thinking twice about them. Everyday speech is full of what Dennett calls “small hand tools,” familiar words and phrases like “wild goose chase” or “feedback” or “slam dunk.” The English language is a tool chest with a million metaphors that serve as a kind of verbal mathematics. They’re informal formulas for describing the way things go. Newton’s equations describe the behavior of a cannonball; “loose cannon” describes the behavior of a certain kind of cannoneer we’ve all had the misfortune to know.

Then there are simple, familiar intuition pumps like Aesop’s “The Boy Who Cried Wolf,” “The Ant and the Grasshopper,” and “The Fox and the Grapes.” We’ve all used those thinking tools too. “Look how much you can say about what somebody has just said by asking, simply, ‘Sour grapes?’” writes Dennett. You can get someone to rethink her position, to consider her situation from a completely different perspective. You can also insult her. (As Dennett observes, “Tools can be used as weapons too.”)

The intuition pumps that he’s created are really philosophical arguments in disguise. Dennett has designed them to push us to see the world his way, and that’s what he’s trying to do by recapitulating them here. “I will not just describe them,” he writes; “I intend to use them to move your mind gently through uncomfortable territory all the way to a quite radical vision of meaning, mind, and free will.”

And his ideas are uncomfortable. His essential claim is that there is no great gulf between nonliving, unconscious gizmos like computers and light switches, on the one hand, and the human brain, on the other. Our strong feeling that there’s something special and inexplicable about consciousness is largely an illusion. It will fade as science advances, like the illusion that the Earth is the center of the universe and everything revolves around us. Biologists used to believe that living things are made of some special material, some elan vital that sets us apart from the stuff of rocks and minerals. Now that we know about DNA, we no longer need an elan vital. Someday we won’t need consciousness either. There’s no metaphysical difference between your body and your mind, or between your laptop and your necktop, so to speak.

That’s a controversial position, obviously. It still feels counterintuitive to most of us, and to most philosophers too, in spite of all of Dennett’s intuition pumps. Does Consciousness Explained explain consciousness, or just explain it away? Check out Dennett’s story “The Sad Case of Mr. Clapgras” and see what you intuit. Mr. Clapgras wakes up one morning and finds that everything he sees is suddenly disgusting. His vision is still normal, but his associations with every color have somehow gone awry overnight. He now hates his old favorite color, red, and prefers his former least favorite, blue. Everything looks the same but nothing feels right. His food looks revolting—he has to eat in the dark. Dennett exploits the tale of poor Mr. Clapgras to raise difficult questions about the nature of perception, and thought, and to disrupt our faith in consciousness itself.

Even if you don’t love logic puzzles, brainteasers, and code-writing, all of which delight Dennett, you may still find this book an entertaining introduction to Dennett’s tenets. As you stretch your mind on his mind-twisters, you begin to feel your way to glimpses of his view of life. At the same time, it’s also something like torture to twist your thoughts into the pretzel-shaped path that Dennett wants you to follow—to walk the Mobius-shaped ribbon of highway on which, no matter how you hurry and scurry ahead, you can never arrive at a place where there is something special about the human mind.

Read this book carefully and you’ll find yourself Jumping Out of the System in all directions. Dennett will lift off the top of your head, and tie your forehead into knots. Is this really where the philosophy of mind is headed? There’s no question that as neuroscience hurtles ahead, our current system of thought is beginning to feel creaky and rusty in the extreme. Some bright new ideas probably are going to have to take its place. It may be that Dennett and his friends are the philosophers who are building them—Dennett most cheerfully of all, in his Santa’s workshop of intuition pumps.

Filed under consciousness Daniel Dennett evolution intuition pump philosophy neuroscience science

174 notes

Gene switches make prairie voles fall in love Epigenetic changes affect neurotransmitters that lead to pair-bond formation. Love really does change your brain — at least, if you’re a prairie vole. Researchers have shown for the first time that the act of mating induces permanent chemical modifications in the chromosomes, affecting the expression of genes that regulate sexual and monogamous behaviour. The study is published today in Nature Neuroscience. Prairie voles (Microtus ochrogaster) have long been of interest to neuroscientists and endocrinologists who study the social behaviour of animals, in part because this species forms monogamous pair bonds — essentially mating for life. The voles’ pair bonding, sharing of parental roles and egalitarian nest building in couples makes them a good model for understanding the biology of monogamy and mating in humans. Previous studies have shown that the neurotransmitters oxytocin and vasopressin play a major part in inducing and regulating the formation of the pair bond. Monogamous prairie voles are known to have higher levels of receptors for these neurotransmitters than do voles who have yet to mate; and when otherwise promiscuous montane voles (M. montanus) are dosed with oxytocin and vasopressin, they adopt the monogamous behaviour of their prairie cousins. Because behaviour seemed to play an active part in changing the neurobiology of the animals, scientists suspected that epigenetic factors were involved. These are chemical modifications to the chromosomes that affect how genes are transcribed or suppressed, as opposed to changes in the gene sequences themselves. Love potion To look for clues of epigenetic agents at play in monogamous behaviour, neuroscientist Mohamed Kabbaj and his team at Florida State University in Tallahassee took voles which had been housed together for 6 hours but had not mated. The researchers injected drugs into the voles’ brains near a region called the nucleus accumbens, which is closely associated with the reinforcement of reward and pleasure. The drugs blocked the activity of an enzyme that normally keeps DNA tightly wound up and thus prevents the expression of genes. The team found that the genes for the vasopressin and oxytocin receptors had been transcribed, and as a result the nucleus accumbens of the animals bore high levels of these receptors. Animals that had been permitted to mate also had high levels of vasopressin and oxytocin receptors, confirming the link between bond formation and gene activity. “Mating activates this brain area which leads to partner preference — we can induce this same change in the brain with this drug,” Kabbaj explains. Interestingly, the injection alone cannot induce the partner preference. “The drug by itself won’t do all these molecular changes — you need the context: it’s the drug plus the six hours of cohabitation,” says Kabbaj. “This is a study I myself wanted to do years ago,” says Thomas Insel, who heads the US National Institute of Mental Health in Bethesda, Maryland. “If mating causes the release of the neuropeptide, how does this kick into a higher gear for the rest of the animal’s life? This study for me really is the first experimental demonstration that the epigenetic change would be necessary for the long-term change in behaviour.” “This paper really shows that there is an epigenetic mechanism underlying pair bonds — we ourselves have looked for that and not found it,” says Alaine Keebaugh of Emory University in Atlanta, Georgia, who also studies the neuroscience of prairie voles. Kabbaj says he hopes that the work could ultimately lead to an enhanced understanding of how epigenetic factors affect social behaviour in humans — not only in monogamy and pair bonding, but also in conditions such as autism and schizophrenia, which affect social interactions.

Gene switches make prairie voles fall in love

Epigenetic changes affect neurotransmitters that lead to pair-bond formation.

Love really does change your brain — at least, if you’re a prairie vole. Researchers have shown for the first time that the act of mating induces permanent chemical modifications in the chromosomes, affecting the expression of genes that regulate sexual and monogamous behaviour. The study is published today in Nature Neuroscience.

Prairie voles (Microtus ochrogaster) have long been of interest to neuroscientists and endocrinologists who study the social behaviour of animals, in part because this species forms monogamous pair bonds — essentially mating for life. The voles’ pair bonding, sharing of parental roles and egalitarian nest building in couples makes them a good model for understanding the biology of monogamy and mating in humans.

Previous studies have shown that the neurotransmitters oxytocin and vasopressin play a major part in inducing and regulating the formation of the pair bond. Monogamous prairie voles are known to have higher levels of receptors for these neurotransmitters than do voles who have yet to mate; and when otherwise promiscuous montane voles (M. montanus) are dosed with oxytocin and vasopressin, they adopt the monogamous behaviour of their prairie cousins.

Because behaviour seemed to play an active part in changing the neurobiology of the animals, scientists suspected that epigenetic factors were involved. These are chemical modifications to the chromosomes that affect how genes are transcribed or suppressed, as opposed to changes in the gene sequences themselves.

Love potion

To look for clues of epigenetic agents at play in monogamous behaviour, neuroscientist Mohamed Kabbaj and his team at Florida State University in Tallahassee took voles which had been housed together for 6 hours but had not mated. The researchers injected drugs into the voles’ brains near a region called the nucleus accumbens, which is closely associated with the reinforcement of reward and pleasure. The drugs blocked the activity of an enzyme that normally keeps DNA tightly wound up and thus prevents the expression of genes.

The team found that the genes for the vasopressin and oxytocin receptors had been transcribed, and as a result the nucleus accumbens of the animals bore high levels of these receptors. Animals that had been permitted to mate also had high levels of vasopressin and oxytocin receptors, confirming the link between bond formation and gene activity.

“Mating activates this brain area which leads to partner preference — we can induce this same change in the brain with this drug,” Kabbaj explains.

Interestingly, the injection alone cannot induce the partner preference. “The drug by itself won’t do all these molecular changes — you need the context: it’s the drug plus the six hours of cohabitation,” says Kabbaj.

“This is a study I myself wanted to do years ago,” says Thomas Insel, who heads the US National Institute of Mental Health in Bethesda, Maryland. “If mating causes the release of the neuropeptide, how does this kick into a higher gear for the rest of the animal’s life? This study for me really is the first experimental demonstration that the epigenetic change would be necessary for the long-term change in behaviour.”

“This paper really shows that there is an epigenetic mechanism underlying pair bonds — we ourselves have looked for that and not found it,” says Alaine Keebaugh of Emory University in Atlanta, Georgia, who also studies the neuroscience of prairie voles.

Kabbaj says he hopes that the work could ultimately lead to an enhanced understanding of how epigenetic factors affect social behaviour in humans — not only in monogamy and pair bonding, but also in conditions such as autism and schizophrenia, which affect social interactions.

Filed under prairie voles mating gene expression neurotransmitters pair bond epigenetics neuroscience science

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