Scientists discover a brain circuit that triggers the execution of planned movement

Planned movement is essential to our daily lives, and it often requires delayed execution. As children, we stood crouched and ready but waited for the shout of "GO!" before sprinting from the starting line. As adults, we wait until the traffic light turns green before making a turn. In both situations, the brain has planned our precise movements but suppresses their execution until a specific cue. Scientists have discovered the brain network that turns plans into action in response to this cue. The brain is like an orchestra. The collective of these sounds shapes a musical phrase. Similarly, neurons in the brain are active with diverse patterns and timing. The ensemble of neuronal activities mediates specific aspects of our behavior. Activity patterns in the motor cortex are dramatically different between the planning and execution phases of movement. The transition between these patterns is critical to trigger movement. Yet, the brain areas controlling this transition are unknown. To identify the neural circuit that serves as the conductor to initiate planned movement, researcher team simultaneously recorded the activity of hundreds of neurons while a mouse performed a cue-triggered movement task. In this task, mice were trained to lick to the right if whiskers were touched or to the left if whiskers were not touched. If the animals licked in the correct direction, they received a reward. However, there was a catch. The animals had to delay their movement until a tone, or "go cue," was played. Only correct movements after the go cue would be rewarded. Therefore, mice maintain a plan of the direction they will lick until the go cue and execute the planned lick after. The scientists then correlated complex neuronal activity patterns to relevant stages of the behavioral task. The researchers found brain activity occurring immediately after the go cue and during the switch between motor planning and execution. This brain activity arose from a circuit of neurons in the midbrain, thalamus, and cortex. To test whether this circuit acted as a conductor, the team used optogenetics. This approach enabled the scientists to activate or inactivate this circuit using light. Activating this circuit during the planning phase of the behavioral task switched the mouse's brain activity from motor planning to execution and caused the mouse to lick. On the other hand, turning off the circuit while playing the go cue suppressed the cued movement. The mice remained in a motor planning stage as if they had not received the go cue.

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                 Evidence suggests cancer is not as purely genetic as thought before

While cancer is a genetic disease, the genetic component is just one piece of the puzzle and researchers need to consider environmental and metabolic factors as well. Nearly all the theories about the causes of cancer that have emerged over the past several centuries can be sorted into three larger groups. The first is cancer as a genetic disease, focusing on the genome, or the set of genetic instructions that you are born with. The second is cancer as an environmental disease, focusing on the exposome, which includes everything your body is exposed to throughout your life. The third is cancer as a metabolic disease, focusing on the metabolome, all the chemical byproducts of the process of metabolism. The metabolic perspective hasn't had much research until now, but it's gaining the interest of more scientists, who are beginning to understand the metabolome's role in cancer. The genome, exposome and metabolome operate together in a feedback loop as cancer develops and spreads. According to the data, heritable cancers account for just 5-10 % of all cancers. The other 90-95 % are initiated by factors in the exposome, which in turn trigger genetic mutations. The metabolome is critical to the process, as those genetically mutated cancer cells are sustained by the cancer-specific metabolome. Cancer is genetic, but often the mutation itself isn't enough. As cancer develops and spreads in the body, it creates its own environment and introduces certain metabolites. It becomes a self-fuelled disease. And that's where cancer as a metabolic disorder becomes really important. The multi-omics perspective, in which the genome, exposome and metabolome are all considered in unison when thinking about cancer, is showing promise for finding treatments and for overcoming the limitations of looking at only one of these factors. For example, researchers who focus only on the genetic perspective are looking to address particular mutations. The problem is, there are around 1,000 genes that can become cancerous when mutated, and it typically takes at least two different mutations within these cells for cancer to grow. That means there are a million potential mutation pairs, and "it becomes hopeless" to narrow down the possibilities when seeking new treatments. But when considering cancer from the metabolic perspective, there are just four major metabolic types. Rather than trying to find a treatment plan for one specific mutation combination amongst a million, determining the patient's cancer metabolic type can immediately guide doctors in deciding on the best treatment for their specific cancer. Researchers cautioned that health-care providers still need a mix of therapeutics for cancer, and noted that a deeper understanding of the metabolome and its role in the cancer feedback loop is also critical to preventing cancer.

SOURCE: Science Daily News, April 2022

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                              Fungal meningitis spreads by blocking and bursting blood vessels

New research from the University of Sheffield, England has revealed how fungus blocks and bursts blood vessels in the brain, helping scientists better understand how meningitis starts. The study, published in the journal PLoS Pathogens, shows that Cryptococcus neoformans microbes become lodged in blood vessels preventing blood flow and increasing blood pressure. These microbes grow in the small blood vessels causing them to stretch and burst, releasing the infectious microbes into the brain and causing meningitis. Meningitis is most commonly caused by an infection of the brain and spinal cord and can be life threatening if not recognized and treated very quickly. It is most common in babies, adolescents and those with compromised immune systems and affects an estimated 2.5 million people each year. The brain has very complex and effective defenses against microbes, but scientists have identified a simple and effective method that microbes may use to escape the blood and enter the brain. Previous research has focused on how microbes can break down the defenses of the brain or use immune cells as a route into the brain. Now it can be can be demonstrated how, for some microbes, damaging blood vessels is a very effective method of invasion. Human body immune system is very effective at recognizing and destroying microbes, including in the blood. However, some microbes can escape the immune cells and it is these microbes that would be most effective at using blood vessels bursting as a way into the brain. The international research team made us to understand how the meningitis infection behaves in blood vessels. The findings will also help researchers better understand other blood vessel related diseases such as cardiovascular and neurological diseases. Scientists started this research because they knew there was unexplained blood vessel damage in some meningitis patients. They are now working to find new treatments for these patients. The infections causing meningitis can be treated with antimicrobials but patients are often very ill and a lot of damage can be caused before treatment is effective. This will be made worse by the ongoing global increase in antimicrobial resistant infections.

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          Migraine Tied to Complications in Pregnancy

Women with migraine may have a higher risk of pregnancy complications like preterm delivery, gestational high blood pressure and preeclampsia, according to a preliminary study. Researchers also found that women with migraine with aura may have a somewhat higher risk of preeclampsia than women with migraine without aura. Roughly 20% of women of childbearing age experience migraine, but the impact of migraine on pregnancy outcomes has not been well understood. This large prospective study found links between migraine and pregnancy complications that could help inform doctors and women with migraine of potential risks they should be aware of during pregnancy. For the study, researchers looked at more than 30,000 pregnancies in roughly 19,000 women over a 20-year period. Of those pregnancies, 11% of the women reported that they were diagnosed by a doctor with migraine before pregnancy. Researchers examined women's complications during pregnancy such as preterm delivery, defined as a baby born before 37 weeks gestation, gestational diabetes, gestational high blood pressure, preeclampsia, and low birthweight. After adjusting for age, obesity, and other behavioral and health factors that could affect the risk of complications, researchers found that when compared to women without migraine, women with migraine had a 17% higher risk of preterm delivery, a 28% higher risk of gestational high blood pressure, and a 40% higher risk of preeclampsia. Of the 3,881 pregnancies among women with migraine, 10% were delivered preterm, compared to 8% of the pregnancies among women without migraine. For gestational high blood pressure, 7% of pregnancies among women with migraine developed this condition compared to 5% among pregnancies in women without migraine. For preeclampsia, 6% of pregnancies among women with migraine experienced it, compared to 3% of pregnancies among women who did not have migraine. In addition, when looking at migraine with and without aura, women who had migraine with aura were 51% more likely to develop preeclampsia during pregnancy than women without migraine, while those who had migraine without aura were 29% more likely. Researchers found that migraine was not associated with gestational diabetes or low birthweight. While the risks of these complications are still quite low overall, women with a history of migraine should be aware of and consult with their doctor on potential pregnancy risks. More research is needed to determine exactly why migraine may be associated with higher risks of complications. In the meantime, women with migraine may benefit from closer monitoring during pregnancy so that complications like preeclampsia can be identified and managed as soon as possible.

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