Optogenetics: Revolutionizing Neuroscience

When you look at other species asides from humans, you begin to notice a general trend amongst between males and females of the population. The females tend to be the ones who care for their offspring after mating, while the males play little or no role in being a parent.

An article posted on Phys.org talks about a research finding showing the relationship between the brain and parental behavior in males and females. In order to do this, researchers chose to focus on specific neurons in the hypothalamus that express tyrosine hydroxylase (TH). TH is essential for the production of dopamine. They noticed that not only were there more TH neurons in mothers compared to virgin females or males, but they had different affects on males and females.

In one of the first few weeks of class, we read about and listened to a discussion on the field of optogenetics. We talked about how the use of optogenetics has opened up many doors in neuroscience and has given us more control when working with complex neural tissues. This article, which was published just last week, is a perfect example of how optogenetics has given scientists more control in their work.

Using optogenetic activation, researchers were able to increase the TH levels in female. And remarkably, within a few minutes, the female mouse went to carry her a pup back to her nest. Increasing the TH levels also showed an increase in oxytocin, a hormone dealing with female reproduction behavior. When the same tactic was tried on male mice, there was no change in patient behavior or oxytocin levels.

The findings show a possibility that the neuronal networks in the brains of males and females can function differently especially in gender-related activities. More importantly, it has shown how researchers were able to manipulate paternal behavior by optogenetics. It is amazing to watch the application of newly discovered scientific technology and methods leading to insightful discoveries like this one.

Works Cited

 How to manipulate the brain to control maternal behavior in females and reduce aggression in males. (2015, October 7). Retrieved October 17, 2015, from http://phys.org/news/2015-10-brain-maternal-behavior-females-aggression.html 

You can have your alcohol and drink it too

Everyone has heard of the phrase: “You can’t have your cake and eat it too.” Well according to a few recent studies, this phrase may be false for a certain delight. What is the God’s nectar on earth? Alcohol of course. Who doesn’t enjoy a nice cold beer during a Thursday night football game? How about a special glass of perfectly aged red wine during dinner with your significant other? Maybe you prefer a few shots with some friends once exams are over. Other than the ecstatic feeling you get from every gulp, imagine that it may be actually good for you in the long run? You might drink right know because you do not know if your liver will last into your 20s, 30s, 40s and on. Let me tell you though, moderation is key. It is becoming more common knowledge that a serving of red wine occasionally is actually beneficial to the cardiovascular and nervous system. But what if I told you that light-to-moderate drinking when you are in your 50s or 60s on can actually reduce your risk of age-dependent cognitive decline? It is always hard seeing a loved one suffer through dementia or Alzheimer’s disease, because not only does it affect that individual, it affects the person’s family and friends as well. I am not saying that let us all go and become alcoholics with the intention of preventing cognitive decline in the future. There is still no doubt that excessive alcohol abuse will definitely cause brain damage and neurological dysfunction. However, a few studies support the belief that mild alcohol consumption is surprisingly beneficial.

            Michael A. Collins and his research team at Loyola University Medical School have researched for several years of the effects of ethanol on rat brain cultures. According to his study, the ethanol “preconditioning” of rat brain cultures prevents neurodegeneration with the suppression of neurotoxic protein-evoked increases in calcium and pro-inflammatory mediators. He finds that the onset of neuroprotection correlates with elevations of effector heat shock proteins, and he found that rats that are preconditioned with ethanol have a higher level elevation of these proteins. It has been indicted in other studies that people who have never drank alcohol are more at risk to cognitive deterioration compared to those that are light or moderate alcohol consumers. From all this, Collins and his team speculate that moderate alcohol intake might actually counter cognitive deterioration during advanced aging by exerting preconditioning-like suppression effects of neuroinflammation. To go along with Collins’ findings, researchers from the University of Texas, University of Kentucky, and University of Maryland investigated the correlation between alcohol consumption in later ages to cognitive abilities. They used data from more than 650 participants that participated with surveys on their alcohol consumption and demographics, neuropsychological assessments, and MRIs. The researchers concluded similar results to that of which Collins speculated, finding that light alcohol consumption during late life is associated with higher episodic memory. More data needs to be collected and interpreted before this theory can be fully supported. But hey, next time you go out for drinks, don’t forget to invite your grandmother. She might remember the night better than you will.

 

References:

B. Downer, Y. Jiang, F. Zanjani, D. Fardo. Effects of Alcohol Consumption on Cognition and Regional Brain Volumes Among Older Adults. American Journal of Alzheimer's Disease and Other Dementias, 2014; DOI: 10.1177/1533317514549411

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.

Cheers to the Fight Against Alzheimer's!

Alzheimer's disease is more than just memory loss.  It is a disease that has the power to take away who you are.  It might start with forgetting appointments, but in the late stage of the disease, you depend on someone else for all your personal needs.  At this point in the disease, you are not able to communicate verbally and might have difficulty eating and swallowing.  As the disease progresses, walking becomes a challenge, which can lead to falling and breaking bones.  But, what if there was hope in giving you a better quality of life?    What if you delay the progression of Alzheimer’s by consuming wine?

A study conducted by Dr. Michael Collins at the Loyola University-Chicago, found that moderate ethanol consumption protects against cognitive decline in neurodegenerative diseases such as Alzheimer’s disease and HIV dementia.   Dr. Collins and his colleagues used rat cultures to study the effects of moderate ethanol preconditioning on neurons and glia cells.  The resulting data revealed that a concentration of 20-30 nM of ethanol, or 4-5 glasses of wine, prevents neurodegeneration caused by β-amyloid.  In Alzheimer’s disease, β-amyloid is a big player.  It is the main component of amyloid plaques found in the brains of those affected with the disease.

In a recent study, it was revealed that resveratrol, an antioxidant found in grapes and red wine, can alter β-amyloid levels in the brain.  Thus, resveratrol can aid in slowing down the progression of Alzheimer’s disease.  In this study, 119 people were given a high dosage resveratrol pill for one year.  The high dosage pill is equivalent to 1000 bottles of red wine!   A high dosage of resveratrol was needed to ensure that enough of it was entering the brain.  It is hypothesized that resveratrol changes the levels of β-amyloid in the brain by circulating it to the rest of the body.  It was noted that people taking the pill found it easier to perform daily tasks such as brushing their teeth. However, much more research is needed to assess its safety and long-term effects. But, it does give us hope in fighting this awful disease! 


 http://www.ncbi.nlm.nih.gov/pubmed/20422315

 http://www.cnn.com/2015/09/11/health/resveratrol-hope-for-alzheimers-patients/

The Pleasure Principle: The Brain Mechanism Involved in Drug Addictive Behavior

  The habitual use of addictive substances can be directly mediated by our brains reward systems. These reward systems in our brain are activated upon our retrieval of food, water, and sexual activity. Engaging in activities that directly excite the reward systems in our brain causes dopamine to be released and elicit a pleasing sensation. Drugs of abuse, specifically act on the brains reward center via the mesolimbic pathway. An area within the mesolimbic pathway, the ventral tegmental area (VTA) is specifically targeted by dopamine and contributes to the reinforcement of drugs of abuse.  In his speech, Dr. Stephen Steidel discussed his research and described how this mechanism is directly shown in mice.

            An electrode was inserted into the midbrain of mice, the excitement of dopamine levels was assessed as the mice were able to self-administer light to their VTA area. Mice were placed in a chamber with two holes, one hole was a control and the other turned on a light directly exciting dopamine neurons ( Steidel). As dopamine neurons excite the VTA, action potentials in the midbrain drastically increase. This mechanism supports how drugs of abuse target dopamine neurons, and reinforces addict’s behaviors by directly mediating on their reward system giving users a pleasing sensation that keeps them coming back for more.

            In an news article CenterCite describes how drugs of abuse, and specifically stimulant drugs keep individuals returning despite their harmful effects on their body “Although different addictions have different effects in the nucleus accumbens, they all activate the reward system. This in turn motivates us to repeat those behaviors, even though they may be harmful”(Horvath).

                                                                        Work Cited

Steidal, Stephan. “Role of laterodorsal tegmental nucleus cholinergic and glutamatergic inputs to ventral tegmental area in reinforcement, drug reward, and sensitization.” Neuroscience Seminar. Loyola University Chicago, Chicago.1Sep.2015.Speech.

Images:

centersite.net/poc/view_doc.php?type=doc&id=48375&cn=1408

Controlling Calcium-- Ion Channels and Familial Alzheimer's

Having the chance to hear Erika Piedras speak of her research on neuronal calcium channels and their relation to leptin resistance and homeostatic mechanisms in mice back in September, I began getting curious about what kind of common ailments and illnesses occur with relation to this type of neuronal system.  Her 2007 paper Voltage-gated calcium channels, calcium signaling, and channelopathies offers insight to the mechanisms of voltage-gated calcium channels (VGCCs), and states some linkages discovered between VGCCs and genetic diseases. Looking further into this topic on the (e) Science News website, I stumbled upon an interesting article about the role of calcium ion channeling and its relationship to familial Alzheimer's disease (FAD).

Research conducted by Kevin Foskett and other researchers at the University of Pennsylvania Perelman School of Medicine has linked genetic mutations in neural presenilin proteins to FAD. This research began when Foskett and colleagues found linkages between presenilin mutations (primarily, those in the PS1 and PS2 proteins) and their interactions with IP3R (the Ca²⁺ ion release channel) in mice: most importantly, that mutated PS1 and PS2 proteins interacted with IP3R receptors in such a way that neural Ca²⁺ ion flow was increased. They began to hypothesize about possible consequences between genetically altered PS proteins with IP3R receptors, and how these mutations could be related to the development of symptoms related to FAD.

By experimenting on mice modeled with FAD and then performing behavioral tests, the team showed that reducing an IP3R receptor (called IP3R₁) by 50% normalized the overexcited Ca²⁺ flow in the hippocampus which, in turn, reduced memory deficits and defective electrical signaling—both of which are common symptoms of FAD and other dementia-related illnesses. This project has shed new light on this genetic condition that affects close to a quarter million Americans, and could offer further connections to the non-genetic Alzheimer’s spectrum that affects another 4.5 million.

Sources:

Piedras, E. (2007, July 27). Voltage-gated calcium channels, calcium signaling, and channelopathies. Retrieved October 10, 2015.

Role of calcium in familial Alzheimer's disease clarified, pointing to new therapeutics. (2014, May 14). Retrieved October 10, 2015, from http://esciencenews.com/articles/2014/05/14/role.calcium.familial.alzheimers.disease.clarified.pointing.new.therapeutics

Image:

http://static-img-d.hgcdn.net/Media/_640x360/DFTIPS144_periodic-table-calcium_FS.jpg

How Mapping and Rewiring Circadian Circuits Converge in Exciting New Rhythms

           The human circadian rhythm, commonly dubbed the “body’s clock,” controls a wide range of physiological processes and overt behaviors, including sleep-wake cycles and environmental responses. Consequently, the body’s clock has an enormous impact on people’s health and how they function. Notably, it influences body temperature, hormone release, metabolism, and is linked to various disorders and diseases, such as insomnia, bipolar disorder, depression, seasonal affective disorder, diabetes, and obesity (nigms.nih.gov/CircadianRhythms). Circadian rhythms are not unique to humans; they have been discovered in most animals, plants, fungi, and cyanobacteria (esciencenews.com/circadian.clock, 2015), and regulate processes akin to those regulated by circadian rhythm in humans. Studying different organisms’ circadian processes allows multiple fields of biology to integrate their developments into current knowledge about human circadian processes, in turn, leading to innovative approaches for regulating physiological behaviors and treating relevant diseases. Consider the implications of the neuroanatomical research conducted by Loyola University Chicago professor, Dr. Daniel J. Cavanaugh, and colleagues (see Cavanaugh et al., 2014), in relation to recent work in genetic engineering led by Harvard University synthetic biologist, Dr. Pamela Silver (see esciencenews.com/circadian.clock, 2015).

            In brief, Cavanaugh et al. focused on mapping neural pathways within the circadian circuit of fruit flies that produce rhythms of physiological behaviors, chiefly the flies’ daily rest/activity cycles. These overt rhythms are produced by the activity of circadian clocks: a system of neurons containing input pathways, which coordinate clock neurons to external cues such as light, and output pathways, which relay time-of-day signals to downstream neurons, thereby modulating rhythmic behavior (2014). Through a random activation of neurons, Cavanaugh et al. screened for relevant circadian clocks and found neurons in the pars intercerebralis (PI) that constitute an important part of the circadian output pathway for fruit fly rest/activity cycles. In addition, they identified DH44, a protein expressed by PI clock neurons, which is necessary for keeping with the flies’ regular overt rhythms (2014). These findings bridge gaps in the current understanding of human circadian circuits inasmuch as the PI is homologous to the mammalian hypothalamus, and DH44 is analogous to the corticotrophin releasing factor (CRF) rhythmically secreted in mammals (2014).

            The work led by Silver (2015), on the other hand, yielded the first successful transplant of a circadian network using genetic engineering. Silver and colleagues engineered a circadian E. coli, a bacterial species that does not have a circadian rhythm in nature. They created the synthetic strain by removing the protein network responsible for regulating circadian rhythms in cyanobacteria, which is circadian in nature, and transplanting it into E. coli  (2015). Once transplanted, the protein network was connected to other factors involved in gene expression in order to manipulate physiological processes relative to the day-night cycle (2015). Silver et al. demonstrated the transplants success using fluorescence, where the circadian protein network was linked to fluorescent proteins, making the E. coli glow in rhythmic unison with its new circadian oscillations (2015). In sum, their work not only revealed the transplantability of a circadian network, but also the ability to manipulate it and its processes in an anticipated manner (2015). Indeed, this novel capability has many applications, especially in medicine. Silver’s ultimate goal is to be able to deliver the synthetic E. coli to patients in pills. Then, the transplanted circadian rhythm should link to other biological networks, and allow for the control of drugs’ release-time in order to get optimal efficiency, or be able to realize and alter a patient’s circadian rhythm (2015). 

           In the direction of furthering current knowledge, multiple fields of scientific study prove not only useful, but also necessary for understanding the multifaceted nature of circadian circuits. Cavanaugh et al.’s research aimed to determine how circadian circuits produce and control physiological behaviors, whereas Silver et al.’s research aimed to tap into circadian circuits for the sake of reprogramming and regulating physiological behaviors. Incidentally, these studies exemplify how advances in various disciplines, like the neural and genetic advances discussed, converge in treatment options for circadian-linked diseases and behaviors.

Setting the Circadian Clock (2015, June 12). In (e) Science News. Retrieved October 
          15, 2015.

Cavanaugh, D. J., Geratowski, J. D., Wooltorton, J. R., Spaethling, J. M., Hector, C. E., 
          Zheng, X., & Johnson, E. C. (2014, April 24). Identification of a circadian 
          output circuit for rest: Activity rhythms in drosophila. Cell, 689-701.