Echoes and Spatial Awareness

It is unbelievable on how much the brain can do for us. It enables the person to experience the reality of the world around us through our senses. But perhaps one of the senses we take for granted is our hearing. Without it, we obviously would not be able to hear music, communicate efficiently, warn us of potential danger, and even help distinguish where the sources of sound is coming and its location. If it wasn’t for our vision to actually see and localize objects, we would primarily rely on our hearing.

How are we able to localize a sound?  Due to the human anatomy, the head is bilateral with the ears at opposite ends. The sound at a given position will travel towards one of the ear at an earlier time and the other ear at a later time. The time difference of the sound is detected and processed to give the direction of the sound source. This is called the interaural time difference (ITD). Also, the difference in sound pressure, the interaural level difference (ILD), is used in accordance in finding direction of source. Based on the research conducted by Dr. Dye and his colleagues, echoes have a masking effect on the source of the sound when the interval between the two falls between 8-64 ms. The echoes itself are considered the new sources of sound, which demands processing resource, thus, the original source of the sound is essentially deleted so that the brain can process this “new” source of sound. 

So how can someone utilize this information? Many people who have lost their sight rely on their hearing to localize their surroundings. Some have it more developed than others to the point where echolocation is used. One notable person who uses this is Daniel Kish. He was born with bilateral retinoblastoma, a cancer in the eye, which resulted in his eyes being removed at the age of seven. As time when on, he learned how to move around in his environment by clicking sounds with his tongue. As he creates a new source of sound in his mouth, he also creates an echo that bounces in the environment and back into his ear. The echoes itself is considered to be new sources of sound due to varying absorption of the environment. This creates patterns which helps him give a relative information of the distance of where the echo is bouncing from. Echolocation mostly work on blind people because of their heightened sense of hearing. Dr. Dye’s results in his research showed that the echo dominated over the source of the sound if the interval falls between 8-64 ms. Seeing how the source of the sound is coming from the individual, it would be beneficial for the echo to be processed over the source since the source is close to our ears. Therefore, the echo provides relative information of the depths of the environment and helping the individual to be spatially aware.

 References:

"Human Echolocation: Using Tongue-clicks to Navigate the World - BBC News." BBC News. N.p., n.d. Web. 17 Oct. 2015.

The influence of later-arriving sounds on the ability of listeners to judge the lateral position of a source. / Dye, Raymond H.; Brown, Christopher A.; Gallegos, José A.; Yost, William A.; Stellmack, Mark A. In: Journal of the Acoustical Society of America, Vol. 120, No. 6, 2006, p. 3946-3956.

Image:

http://media1.s-nbcnews.com/j/MSNBC/Components/Photo/_new/090707_ear-echolocation.grid-6x2.jpg 

What is Optogenetics?

What is Optogenetics?

Optogenetics is the new, trendy method for scientists to use in order to precisely control specific areas in any population of cells for any species. This method utilizes UV light( ultra-violet light) at a specific wavelength to activate/deactivate light-sensitive proteins in particular areas within the cell. By activating/deactivating these proteins ion pumps, the movement of these ions, cations and anions, across the membrane greatly affects the the communication between neurons. By shining light to these proteins, scientists will be able to manipulate what areas of the cells will and will not be active.

In the neuroscience seminar, Dr.Stephan Steidl presented his research on how he uses Optogenetics when experimenting on the dopamine system. The dopamine pathway, which is also called the mesolimbic dopamine system, is a pathway inside the brain that controls the brain’s pleasure and rewards. Dr.Steidl took rats and injected them with adeno -associated viral vectors, AAV, into certain part of the brain. Once the AVV has been injected, the neurons in the area became light-sensitive. Later, a thin wire that had a light source would be put into the dopamine pathway(inside the brain) where the neurons were light-sensitive. Researchers would then turn on the light, and thus the light would then activate the dopamine pathway. With the help of optogenetics, researchers were able to purposefully manipulate the rat’s brain by turning on the dopamine pathway. I personally found it shocking because once it was on, it seemed like the rats had no control over themselves. The rats with their pathways on were continuously electrically shocked many times, yet the rats didn’t care that they were being harmed.

A recent research has come out that with the help of optogenetics, memory can be improved. This research, coming from the Korean Institute of Science and Technology, indicates that optogenetics can precisely control the calcium channels. Calcium channels are ion gated protein channels in the membrane that are responsible for transporting calcium in and out of the cell. It is important that calcium ions be kept at a particular concentration both inside/outside the cell since they are responsible for cognitive functioning. The researchers were able to use a hybrid, photoreceptor molecule called OptoSTIM1, and they placed the molecule into the mice’s brain and shined blue light into the area. They found that by shinning the blue light onto this specific hybrid molecule, the calcium ion channels were forced to open up and take more calcium into the cell than previous molecules in past experiments had. Just like Steidl had manipulated optogenetics to turn on the dopamine pathway, researchers had shined light to turn on the calcium ion channels for improvement in memory. Once of the researchers saw that the molecule improved in calcium uptake, they then hypothesized that their new hybrid molecule can greatly benefit those with Alzheimer’s  disease since it is the dysfunction in calcium regulation.  This shows that optogenetics is a very crucial tool for scientists because of how successful it has been, yet I believe that more research involving optogenetics in other areas besides the brain will tell how successful this tool really is.

Heo, Won Do, and Yong Mahn Han. "Improving Memory With a Flash of Light." PHYS.ORG. Nature Biotechnology, 14 Sept. 2015. Web.

Pulling an All-Nighter Could Be Making Your Pants Tighter

            We’ve all been in a situation where we’ve had to pull an all-nighter or two. Caffeine is flowing, blood is pumping, and sweat is dripping, all in the hopes that it’s worth it after the exam. But the underlying question is whether or not getting a grade is worth stressing your body and disrupting your internal clock is worth it? Would it be smarter to study a few days prior rather than cramming the night before? This ensures that you are sleeping when its time to sleep and working when its time to work. We’ve always used night and day to distinguish when we should sleep, that’s the way we were taught, and this is because light and dark cues are one of the biggest factors in terms of regulating our circadian rhythms in our bodies.

Our body is all synched up to one central clock, the Superchiasmatic  Nucles(SCN), which is found in the hypothalamus near the crossing of the optic nerves. The mere fact that it is so close to the optic nerves explains why these light and dark cues are so prevalent in determining the clock in which all of our body’s clocks are synched with.  Yes, there is not just one clock in the body, different parts on our body need to function at different times and therefore have molecular timing mechanisms of their own, but in the end they all report to the SCN. Some clocks are regulated by external stimulus, whereas others are due to a constant internal time keeping mechanism.

In the morning, the body is physically preparing itself to metabolize nutrients to have enough energy to meet the demands of the day and so it is a good idea to eat a decent breakfast. At night the body is preparing itself for sleep so it starts shutting off these energy expensive processes a few hours before you usually sleep in anticipation. Allison Andrews explains, “the clock in the pancreas, for instance, has to start releasing insulin to deal with the meal. And, research suggests, this late-night munching may start to reset the clock in the organ. The result? Competing time cues.” The competition in these cues leads homeostatic irregularities that can lead to obesity or even Type 2 Diabetes if these irregularities happen often enough.

In our Neuroscience 300 seminar, Dr. Cavanaugh explained a paper that stated, “During sleep, flies exhibit reduced activity/movement and reduced responsiveness to sensory stimulation. In addition, sleep deprivation results in a subsequent increase in sleep amount and intensity, indicating homeostatic regulation. Pharmacological and genetic evidence suggests that the underlying mechanisms of Drosophila sleep are similar to those in mammals.” His work on the circadian rhythm is moving us towards a greater understanding of the mechanisms under circadian control in flies, which in turn could lead to some insight on how our circadian control works. If he wants to keep doing this for a long time, he should realize its just as important to get a good nights sleep and eat a healthy breakfast in the morning as it is to crunch numbers.

Works Cited:

Aubrey, Allison. "Circadian Surprise: How Our Body Clocks Help Shape Our Waistlines." NPR. NPR, 10 Mar. 2015. Web. 16 Oct. 2015.

http://www.npr.org/sections/thesalt/2015/03/10/389596946/circadian-surprise-how-our-body-clocks-help-shape-our-waistlines

Genes Can Influence Weight Gain and Obesity... Through the Brain

Frequently, obesity and weight gain are linked to genetics in conjunction with eating habits and activity. Hormones, such as leptin, regulate many different functions in our body, usually either directly through the hypothalamus or through another organ such as the thyroid in conjunction with the hypothalamus. Leptin is a feedback hormone that holds importance in this area of interest, as it maintains homeostasis in adipose (fatty tissue) by regulating thermogenesis (the generation of heat in the body), feelings of satiety and hunger, increase energy expenditure, and the "reward value" associated with certain nutrients in food. Due to this, leptin sensitivity became a focal point for research regarding obesity. 

Dr. Piedras of Loyola University Chicago Stritch School of Medicine recently spoke about her research regarding down-regulating production of KLHL1 proteins, which affect calcium channels in certain types of neurons, resulting in an imbalance of excitatory and inhibitory synapses, favoring inhibitory synaptic activity. In order to better study the effect of a mutant gene that down regulates KLHL1 protein,  Dr. Piedras' team studied wild type mice and mice with a KO mutant neurons (down regulating the KLHL1 protein), and their study found that mice with the KO mutation gained more weight and at a faster pace than the wild type mice upon reaching adulthood, even when fed the same diet. 

Other studies have found similar results when the genes that concern leptin are affected. In the picture above, the mouse on the left is homozygous for a gene that causes insensitivity to leptin in the brain. These (db/db) mice quickly develop type II diabetes and obesity, unlike the mice sensitive to leptin.  

Giving leptin to patients with mutations that cause leptin insensitivity is unlikely to produce positive results. Instead, some scientists are looking into using a direct orexin receptor antagonist. Such a drug would prevent or hinder the release of orexin, which causes feelings of hunger, which may possibly help with treating obesity in patients with leptin insensitivity. Obesity is a multi-faceted problem, and a few of those facets are in the brain. By researching neural pathways and genetics, science can hope to explore the causes of and find chemical solutions for many conditions, including obesity. By using the knowledge we as scientists have, we can explore solutions to our problems and ask the important questions about what comes next, until somewhere in the web of new information we find our solution. Perhaps that next solution will be the regulation of obesity and the genes that cause it, and perhaps that answer to curing obesity does indeed lie in our neurons and the hormones that regulate them. 

Works Cited

"Cell Calcium: down-regulation of endogenous KLHL1 decreases voltage-gated calcium current density." Elsevier. 9 March 2014. 

Scicurious. "Orexin and Binge Eating Rats." Scientific American. Scientific American, 17 Sept. 2012. Web. <http://blogs.scientificamerican.com/scicurious-brain/orexin-and-binge-eating-rats/>.

Piccoli L, Micioni Di Bonaventura MV, Cifani C, Costantini VJ, Massagrande M, Montanari D, Martinelli P, Antolini M, Ciccocioppo R, Massi M, Merlo-Pich E, Di Fabio R, & Corsi M (2012). Role of orexin-1 receptor mechanisms on compulsive food consumption in a model of binge eating in female rats. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 37 (9), 1999-2011 PMID: 22569505

Image: https://upload.wikimedia.org/wikipedia/commons/0/0b/Fatmouse.jpg

Cheers To Good Health

In elementary school, we go through anti substance abuse programs like DARE and GREAT. From an early age American children are exposed to the atrocities of alcohol and drugs. We are conditioned to stay away from intoxicating substances as they lead to grave health issues in the future. However, recent studies are beginning to crack the surface of the benefits of alcohol. Scientists are unraveling new evidence pointing to the study that alcohol may in fact prevent Alzheimer’s and other health related issues.

In a recent study published in the Annals of internal Medicine, it states that “drinking a moderate amount of wine can be good for your health.” Researchers studied people with diabetes for two years to come up with this conclusion. In A Glass Of Wine A Day May Help Control Type 2 Diabetes, Allison Aubrey explains that in the experiment, the test subjects were all eating the same types of food but there was a group of individuals who drank red wine with their meal, another group who drank white wine, and the third group drank mineral water. At the end of the two year period, researchers discovered that the red wine drinkers had better cardiovascular health as well as “improve[ed] levels of good cholesterol.”

These findings tie in with Dr. Michael Collin’s study on the connection between Alzheimer’s and alcohol. In his research, Dr. Collins concluded that in comparison to those who abstain, alcohol consumption in moderation shows a lower risk for cognition related diseases like Alzheimer’s. His studies attribute this to the brain’s affinity to moderate use of ethanol intake which correlates with brain glia and neurons. To test his hypothesis, Dr. Collins experimented on rats. He saw that when the rats were preconditioned with moderate ethanol, there brain cultures did not go through neurodegeneration. When something is preconditioned, a toxin is exposed to a sub lethal environment so the toxin generates a neuroprotective state. Neurodegeneration occurs when there is a loss of function or structure in the neurons. This can occur for a variety of factors such as untimely phosphorylation of Tau proteins. Through his experimentation, Dr. Collins and his fellow researchers found that rats that had been exposed to moderate alcohol were less likely to get Alzheimer’s disease.

With all of these studies indicating the positives of alcohol, it is important to take note of the one common theme: moderation. Too much alcohol still presents people with a plethora of diseases and health related issues. From a long slew of articles providing evidence against alcohol, there is no doubt that alcohol in excess can lead to many complications. Because alcohol is absorbed into the bloodstream, blood carries the toxins throughout the entire body thus extremely affecting one’s health. When alcohol is consumed, the liver and pancreas have to work twice as hard to expel it from the system. Overuse of alcohol has short term side effects but over time, those short term effects can become permanent. Researchers are using their findings to educate people on alcohol in moderation.

Works Cited

Collins, M., Neafsey, E., Wang, K., Achille, N., Mitchell, R., & Sivaswamy, S. (2010). Moderate Ethanol Preconditioning of Rat Brain Cultures Engenders Neuroprotection Against Dementia-Inducing Neuroinflammatory Proteins: Possible Signaling Mechanisms. Molecular Neurobiology Mol Neurobiol, 420-425

"A Glass Of Wine A Day May Help Control Type 2 Diabetes." NPR. NPR, n.d. Web. 17 Oct. 2015.
http://www.npr.org/sections/thesalt/2015/10/14/448311831/diabetes-study-adds-evidence-that-a-glass-of-wine-is-good-for-you

The Future of Neurological Tools: Sonogenetics

One of the topics I was interested in was Dr. Steidl's talk on optogenetics. Optogenetics is a great tool that lets us turn neurons on or off with various pulses of light. As the contents of our toolbox grow, the opportunities for neuroscience continue to grow. The microbial opsin method shows that light-induced inward cation currents may be used to depolarize the neuronal membrane and positively modulate firing of action potentials, whereas optical pumping of chloride ions can induce outward currents and membrane hyperpolarization, which negatively modulates the firing of action potentials. These tools may be used to target specific subpopulations of neurons within tissues, which is very useful. However, our tools are still expanding and we have discovered a new method to control neurons.

An article in  The Guardian talks about the advent of "sonogenetics", which allows the use of ultrasound to activate brain, heart, and muscle cells from outside the body. Scientists have bred worms with genetically modified nervous systems that can be controlled by bursts of sound waves. The nematodes change direction the moment they are blasted with sonic pulses that are too high-pitched for humans to hear. This happens because the pulses switch on motor neuron cells that are genetically modified to carry membrane channels that respond to ultrasonic waves. The worms do not normally respond to ultrasound, but they do when surrounded by a fluid containing microscopic bubbles. These bubbles seem to amplify the ultrasonic waves which then pass inside the worms.

The amplified ultrasound waves act on structures known as TRP-4 ion channels, found in the membranes of some of the worms' cells. According to a report in Nature Communications, the sound waves make these ion channels open up and activate the cells they are attached to.

This procedure has advantages to optogenetics, in that optogenetics requires light to be sent down an optic fiber to the desired location inside the brain, whereas low frequency ultrasound waves can pass through tissue unhindered, and can be sent into the brain from on top of the skull.

Demonstration of Sonogenetics

Wine Can Fight Alzheimer's?

         

          What does it mean to be closer to finding the cure for diseases that no one has truly been able to understand?  Alzheimer’s disease (AD) and other non-inheritable dementias may not all have one specific cause or origin, yet they may all have certain pathways in common.  Many researchers have dedicated years of extensive research in an attempt to map out the neural circuitry of the brain.  Contrary to popular opinion, there is so little we really know when it comes to how the brain functions in relation to many diseases. 

          In correspondence to the same mission, much light has been recently shed on the study of neuroprotection in the brain and the underlying mechanisms behind the regulation of specific proteins. Dr. Michael Collins came to Loyola University Chicago on October 13, 2015 to speak about his research on ethanol preconditioning and brain neuroprotective signaling.  Moderate ethanol preconditioning (MEP) was applied to cultures of rat brains in order to study possible mechanisms that can provide neuroprotection to the brain.  About 20 to 30mM of ethanol seemed to cause neuroprotection by preventing the effects of neurotoxic proteins.

          The first part of this study focused on trying to understand the mechanisms that would lead to a neuroprotective state in the brain.  Specifically, MEP was seen to cause changes in NMDA receptor activity.  Any major increase or decrease in activity of this receptor was also seen to increase activity in PKC.  Upstream PKC activity corresponded to increased activity of another tyrosine phosphorylating enzyme, FAK.  Finally, this leads to increased activity in the antioxidant protein, peroxiredoxin 2 (Prx2), which corresponds to a neuroprotective state of the brain. 

          The second part of this study focused on taking this new information a step further and charting into the unknown.  Previous studies were seen to show a similar mechanism in terms of trans-reservatrol, the natural compound found in red wine.  Trans-reservatrol also increased activity of the Prx2 enzyme causing protection from beta amyloids.  It was found that 5 ɥM of this compound lead to neuroprotection.  Now, the big question was if one could synergize the preconditioning modalities combinatorially?  Combining 10 mM of ethanol and 5 ɥM reservatrol actually decreased death of neurons down to 10 percent! 

          It turns out that Dr. Collin’s study was not the only one interested in the neuroprotection made possible by trans-reservatrol.  In fact, just last year the Journal of Alzheimer’s Disease published a study that analyzed the protein, Sirtuin 1.  The activity of this protein increases with added amounts of reservatrol.  Dr. Porquet and researchers at the University of Barcelona fed a dietary supplementation amount of reservatrol for 10 months to a group of mice that were modified to develop Alzheimer’s disease.  According to Mercè Pallàs, researcher from the Research Group on Aging and Neurodegeneration of UB and the Centre for Networked Biomedical Research on Neurodegenerative Diseases (CIBERNED), “Results showed that reservatrol ameliorated short-term memory and stopped the accumulation of senile plaques and the development of the tau protein, the two most important characteristics of the disease.”  Analysis of the Sirtuin pathway in terms of reservatrol emphasizes the importance reservatrol has on neuroprotection for the brain.  This study in combination with Dr. Collin’s research shows that understanding the different mechanisms and pathways which influence a single response is much more complex than originally predicted.  It also opens up uncharted territory in terms of explanations for different non-inheritable mental illnesses. 

References:

file:///C:/Users/shibu/Downloads/Mitchell.BrainRes2015%20(3).pdf

http://www.sciencedaily.com/releases/2014/09/140918091032.htm

Images:

http://www.americannursetoday.com/wp-content/uploads/2014/07/brain-tree-dementia-624x295.jpg

http://static1.squarespace.com/static/54ced80ee4b0aa862f974cbf/t/5612c9e1e4b0521c7947e56f/1444071911236/redwinehealthbenefits.jpg?format=750w

Circadian Rhythm: Drosphilia and Humans

Our circadian rhythm regulate how our body functions throughout the day. It is one of our fundamental rhythms that regulate our whole body. In addition, our ability to sleep is also related to our circadian rhythm. Sleep and circadian rhythms are one of the most heavily researched topics. Our circadian rhythm not only affects our sleep schedule and cycle, but as well as our ability to eat at certain times during the day and night, and how alert we tend to be.  They can affect our physical, mental, and behaviour throughout our 24-hour cycle. In a study done by Ravi Allada and Brian Y. Chung, drosophila was researched in order to research the output pathways that couple clock cells to overt behaviours. This is similar to a study done by researchers at the University of Colorado Boulder about caffeine and the body’s internal clock.

In Allada’s and Chung’s study, Circadian Organization of Behavior and Physiology in Drosophila, an experiment is conducted in order to research the output pathways that couple clock cells to overt behaviours. This was done through searching for circadian relevant neurons in the brain and creating an output pathway for rest:activity rhythms. For all of the tests, however, it was shown that all sorts of cell ablation and cell stimulation never altered the functions of the clock cells in the Drosophila. In order to examine this, various PI cells were studied and were connected to a clock through a circuit that connected the pacemaker cells to the PI neurons. Also, a corticotropin releasing factor was studied as well. It was found that a neuropeptide called PDF affected the certain types of behavioural rhythms in the flies and a loss of molecular rhythms in the clock cells. Also, a large subset of the pacemaker that was studied indicate that when stimulated, it promoted arousal. In addition, they also studied individual clock cells and sometimes suppressed them. By suppressing different clock cells and clock functions in different areas, the researchers were able to see the responses to light, mating, sleep, and learning and memory. By looking at all the systems and how they connected to the circadian rhythms, they were able to conclude that these rhythms throughout the body (light, mating, sleep, learning, memory, feeding, etc) were directly correlated with the clock cells in the flies.

With circadian rhythms in humans, however, we tend to respond to light and darkness in order to control our biological clock. Our biological clock controls our circadian rhythms through groupings of molecules in cells that interact together all throughout the body. The suprachiasmatic nucleus in our brain is our master clock. In a study done at University of Colorado Boulder, it was shown that caffeine disrupts the body’s internal clock. Five volunteers were randomly assigned to consume as much caffeine in a double espresso three hours before their bedtime, were exposed to bright lights, or given a placebo. Throughout 49 days, they were studied and their melatonin levels were also studied as well. Those volunteers who took caffeine in low-light conditions ended up experiencing a 40-minute phase delay of the circadian rhythm. Those were who were exposed to bright lights had their circadian clocks go back by 85 minutes. Those who were under both conditions, caffeine and bright lights, had their circadian rhythm disrupted by 105 minutes. With the circadian rhythm being shifted later, it was concluded that the caffeine also affected the physiology of humans because when the circadian rhythm is shifted back, it can affect behaviour and physical processes throughout the day. It usually results in slower behavioural processes and physical movement. Therefore, the presence of caffeine changed their circadian rhythm.

When looking at the study of the Drosophila and the study with the caffeine, it can be concluded that the circadian rhythm can drastically change with humans, but that the circadian rhythm is a lot more complicated with Drosophila. With the flies, the clock cells controlled many different other rhythms throughout the flies: eating, mating, sleep, courtship, etc. However, with humans, it was shown that one drug could affect the whole circadian rhythm and completely disrupt it. However, both studies show the importance of the circadian rhythm and the effect of it throughout the entire body. For flies, the circadian rhythm is connected to all other systems throughout the fly. For humans, the circadian rhythms are still connected to our mental, physical, and behavioural processes. Therefore, any disruption to our circadian rhythm can heavily affect our regular body system. These two research studies directly tell us that our circadian rhythm should not be faltered with and the importance of our circadian rhythm overall. 

Allada, R., & Chung, B. (2010). Circadian Organization of Behavior and

Physiology of Drosophila. The Annual Review of Physiology.

doi:10.1146/annurev-physiol-021909-135815

Coffee at night disrupts body's internal clock: Study - The Economic Times. (2015, September 17). Retrieved October 16, 2015, from http://economictimes.indiatimes.com/magazines/panache/coffee-at-night-disrupts-bodys-internal-clock-study/articleshow/48995541.cms