Posts tagged mammalian brain
Articles and news from the latest research reports.
Toxoplasma infection permanently shifts balance in cat-and-mouse game
The toxoplasma parasite can be deadly, causing spontaneous abortion in pregnant women or killing immune-compromised patients, but it has even stranger effects in mice.
Infected mice lose their fear of cats, which is good for both cats and the parasite, because the cat gets an easy meal and the parasite gets into the cat’s intestinal tract, the only place it can sexually reproduce and continue its cycle of infection.
New research by graduate student Wendy Ingram at the University of California, Berkeley, reveals a scary twist to this scenario: the parasite’s effect seem to be permanent. The fearless behavior in mice persists long after the mouse recovers from the flu-like symptoms of toxoplasmosis, and for months after the parasitic infection is cleared from the body, according to research published today (Sept. 18) in the journal PLoS ONE.
“Even when the parasite is cleared and it’s no longer in the brains of the animals, some kind of permanent long-term behavior change has occurred, even though we don’t know what the actual mechanism is,” Ingram said. She speculated that the parasite could damage the smell center of the brain so that the odor of cat urine can’t be detected. The parasite could also directly alter neurons involved in memory and learning, or it could trigger a damaging host response, as in many human autoimmune diseases.
Ingram became interested in the protozoan parasite, Toxoplasma gondii, after reading about its behavior-altering effects in mice and rats and possible implications for its common host, the domesticated cat, and even humans. One-third of people around the world have been infected with toxoplasma and probably have dormant cysts in their brains. Kept in check by the body’s immune system, these cysts sometimes revive in immune-compromised people, leading to death, and some preliminary studies suggest that chronic infection may be linked to schizophrenia or suicidal behavior.
Pregnant women are already warned to steer clear of kitty litter, since the parasite is passed through cat feces and can cause blindness or death in the fetus. One main source of spread is undercooked pork, Ingram said.
With the help of Michael Eisen and Ellen Robey, UC Berkeley professors of molecular and cell biology, Ingram set out three years ago to discover how toxoplasma affects mice’s hard-wired fear of cats. She tested mice by seeing whether they avoided bobcat urine, which is normal behavior, versus rabbit urine, to which mice don’t react. While earlier studies showed that mice lose their fear of bobcat urine for a few weeks after infection, Ingram showed that the three most common strains of Toxoplasma gondii make mice less fearful of cats for at least four months.
Using a genetically altered strain of toxoplasma that is not able to form cysts and thus is unable to cause chronic infections in the brain, she demonstrated that the effect persisted for four months even after the mice completely cleared the microbe from their bodies. She is now looking at how the mouse immune system attacks the parasite to see whether the host’s response to the infection is the culprit.
“This would seem to refute – or at least make less likely – models in which the behavior effects are the result of direct physical action of parasites on specific parts of the brain,” Eisen wrote in a blog post about the research.
“The idea that this parasite knows more about our brains than we do, and has the ability to exert desired change in complicated rodent behavior, is absolutely fascinating,” Ingram said. “Toxoplasma has done a phenomenal job of figuring out mammalian brains in order to enhance its transmission through a complicated life cycle.”
(Source: newscenter.berkeley.edu)
Birds and humans have similar brain wiring
You may have more in common with a pigeon than you realise, according to new research.
It shows that humans and birds have brains that are wired in a similar way.
A researcher from Imperial College London and his colleagues have developed for the first time a map of a typical bird brain, showing how different regions are connected together to process information. By comparing it to brain diagrams for different mammals such as humans, the team discovered that areas important for high-level cognition such as long-term memory and problem solving are wired up to other regions of the brain in a similar way. This is despite the fact that both mammal and bird brains have been evolving down separate paths over hundreds of millions of years.
The team suggest that evolution has discovered a common blueprint for high-level cognition in brain development.
Birds have been shown in previous studies to possess a range of skills such as a capacity for complex social reasoning, an ability to problem solve and some have even demonstrated the capability to craft and use tools.
Professor Murray Shanahan, author of the study from the Department of Computing at Imperial College London, says:
“Birds have been evolving separately from mammals for around 300 million years, so it is hardly surprising that under a microscope the brain of a bird looks quite different from a mammal. Yet, birds have been shown to be remarkably intelligent in a similar way to mammals such as humans and monkeys. Our study demonstrates that by looking at brains that are least like our own, yet still capable of generating intelligent behaviour, we can determine the basic principles governing the way brains work.”
The team developed their map by analysing 34 studies of the anatomy of the pigeon brain, which is typical for a bird. They focussed on areas called ‘hub nodes’, which are regions of the brain that are major centres for processing information and are important for high level cognition.
In particular, they looked at the hippocampus, which is important for navigation and long-term memory in both birds and mammals. They found that these hub nodes had very dense connections to other parts of the brain in both kinds of animal, suggesting they function in a similar way.
They also compared the prefrontal cortex in mammals, which is important for complex thought such as decision making, with the nidopallium caudolaterale, which has a similar role in birds. They discovered that despite both hub nodes having evolved differently, the way they are wired up within the brain looks similar.
The long-term goal of the team is to use the information generated from the wiring diagram to build computer models that mimic the way that animal brains function, which would be used to control a robot.
The study was published this month in the Frontiers in Computational Neuroscience journal.
Brain capable of making its own version of Valium
The oral drug Valium – also known by its generic name, diazepam – was once popular with doctors in the 1970s as a treatment for seizures brought on by epilepsy. However, the drug, also used to treat anxiety, has fallen out of favor in recent years as it is prone to abuse and often dangerous if taken in high doses.
Now, in light of a recent study, the need for Valium to treat epilepsy may be even further diminished. Researchers from Stanford University School of Medicine have discovered a naturally occurring protein in the brains of mammals that acts like Valium, stopping certain types of seizures from occurring. Researchers hope that if they are able to discover a way to boost this protein naturally, doctors would no longer have a need to prescribe Valium.
The protein, identified as diazepam binding inhibitor (DBI), essentially acts like the brain’s very own brake system, sensing when a seizure is about to occur and arresting the process before it can spiral out of control.
“Our thinking on brain circuits and epilepsy has been that our brains have their own ways to control seizures, and this is why most of us aren’t having seizures every day,” study author John Huguenard, professor of neurology and neurological sciences at Stanford, told FoxNews.com. “But what happens as a seizure starts, a few cells in the brain may get too active, and you get an avalanche of activity that eventually can take up most of the brain circuitry. The brain’s own ‘Valium’ is acting as an anti-avalanche method, checking things when they’re first starting.”
According to Huguenard, the brain has two main groups of nerve cells. The first type of cells – excitatory cells – are responsible for stimulating other cells and sending messages from one area of the brain to another. This messaging process, known as excitation, is responsible for communicating what we see, what we smell, what we do, etc.
The other key type of cells are known as inhibitory cells, which are responsible for keeping the brain circuitry under control. If one area of the brain gets too excited and starts to receive too many signals at once, the inhibitory cells kick into gear and slow the process in order to restore balance.
“In terms of this form of epilepsy we’ve been studying, if a certain group of brain cells can’t communicate well through this inhibitory process, then (the animals) have seizures,” Huguenard said.
The protein DBI is a crucial component of the inhibitory process, as it boosts the actions of an important neurotransmitter called gamma-aminobutyric acid (GABA). Roughly one-fifth of the inhibitory nerve cells in the brain operate by secreting GABA, which binds to receptors located on excitatory cells, rendering them temporarily unable to fire any more electrical signals.
Without DBI, GABA cannot be enhanced, and the excitatory cells ultimately don’t get the message telling them to calm down. However, up until now, this function of DBI was not well understood by researchers.
To determine exactly how DBI operates in the brains of mammals, Huguenard and his team analyzed a group of bioengineered mice with the DBI gene mutation, meaning their brains were incapable of producing DBI.
“When we tested seizures in these animals and tested communication, we found that (the inhibitory process) was ineffective and that the animals had more seizures,” Huguenard said. “It told us that this gene is producing a product in the brain that is controlling the seizures.”
When they re-introduced the DBI-gene back into the brains of these mice, GABA-induced inhibition was restored and the mice suffered from fewer seizures.
Benzodiazepine drugs, like Valium, work in a very similar way to DBI by also enhancing GABA-induced inhibition. But they often come at a high cost. Many who take these medications long-term develop a physical dependence on the drug, experiencing serious withdrawal symptoms if they cease taking it. Some studies have also found Valium to have an adverse effect on both short-term and long-term cognition.
While the researchers only examined the brains of mice, they are optimistic DBI exists similarly in the brains of humans as well. If the results end up translating to the human mind, Huguenard hopes to find a way to naturally boost DBI in the brain, negating the need for Valium to help control seizures.
“The ultimate goal would be to develop new lines of therapy that would take this general approach – taking the brain’s mechanism for dealing with seizures and making them even more effective,” Huguenard said.
The research was published May 30 in the journal Neuron.
How the brain folds to fit
During fetal development of the mammalian brain, the cerebral cortex undergoes a marked expansion in surface area in some species, which is accommodated by folding of the tissue in species with most expanded neuron numbers and surface area. Researchers have now identified a key regulator of this crucial process.
Different regions of the mammalian brain are devoted to the performance of specific tasks. This in turn imposes particular demands on their development and structural organization. In the vertebrate forebrain, for instance, the cerebral cortex – which is responsible for cognitive functions – is remarkably expanded and extensively folded exclusively in mammalian species. The greater the degree of folding and the more furrows present, the larger is the surface area available for reception and processing of neural information. In humans, the exterior of the developing brain remains smooth until about the sixth month of gestation. Only then do superficial folds begin to appear and ultimately dominate the entire brain in humans. Conversely mice, for example, have a much smaller and smooth cerebral cortex.
“The mechanisms that control the expansion and folding of the brain during fetal development have so far been mysterious,” says Professor Magdalena Götz, a professor at the Institute of Physiology at LMU and Director of the Institute for Stem Cell Research at the Helmholtz Center Munich. Götz and her team have now pinpointed a major player involved in the molecular process that drives cortical expansion in the mouse. They were able to show that a novel nuclear protein called Trnp1 triggers the enormous increase in the numbers of nerve cells which forces the cortex to undergo a complex series of folds. Indeed, although the normal mouse brain has a smooth appearance, dynamic regulation of Trnp1 results in activating all necessary processes for the formation of a much enlarged and folded cerebral cortex.
Levels of Trnp1 control expansion and folding
“Trnp1 is critical for the expansion and folding of the cerebral cortex, and its expression level is dynamically controlled during development,” says Götz. In the early embryo, Trnp1 is locally expressed in high concentrations. This promotes the proliferation of self-renewing multipotent neural stem cells and supports tangential expansion of the cerebral cortex. The subsequent fall in levels of Trnp1 is associated with an increase in the numbers of various intermediate progenitors and basal radial glial cells. This results in the ordered formation and migration of a much enlarged number of neurons forming folds in the growing cortex.
The findings are particularly striking because they imply that the same molecule – Trnp1 – controls both the expansion and the folding of the cerebral cortex and is even sufficient to induce folding in a normally smooth cerebral cortex. Trnp1 therefore serves as an ideal starting point from which to dissect the complex network of cellular and molecular interactions that underpin the whole process. Götz and her colleagues are now embarking on the next step in this exciting journey - determination of the molecular function of this novel nuclear protein Trnp1 and how it is regulated. (Cell 2013)
(Source: en.uni-muenchen.de)
Neuroprosthesis gives rats the ability to ‘touch’ infrared light
Researchers have given rats the ability to “touch” infrared light, normally invisible to them, by fitting them with an infrared detector wired to microscopic electrodes implanted in the part of the mammalian brain that processes tactile information. The achievement represents the first time a brain-machine interface has augmented a sense in adult animals, said Duke University neurobiologist Miguel Nicolelis, who led the research team.
The experiment also demonstrated for the first time that a novel sensory input could be processed by a cortical region specialized in another sense without “hijacking” the function of this brain area said Nicolelis. This discovery suggests, for example, that a person whose visual cortex was damaged could regain sight through a neuroprosthesis implanted in another cortical region, he said.
Although the initial experiments tested only whether rats could detect infrared light, there seems no reason that these animals in the future could not be given full-fledged infrared vision, said Nicolelis. For that matter, cortical neuroprostheses could be developed to give animals or humans the ability to see in any region of the electromagnetic spectrum, or even magnetic fields. “We could create devices sensitive to any physical energy,” he said. “It could be magnetic fields, radio waves, or ultrasound. We chose infrared initially because it didn’t interfere with our electrophysiological recordings.”
Nicolelis and colleagues Eric Thomson and Rafael Carra published their findings February 12, 2013 in the online journal Nature Communications. Their research was sponsored by the National Institute of Mental Health.