Chris Moore Lecture
Amina Kureshi
Neuroscience Across the Curriculum
Neuroscientist Chris Moore recently gave a talk on Trinity’s campus about his research on the Hemo-Neural Hypothesis. As stated in the paper he co-wrote (Moore & Cao 2008), Moore describes the phenomena of increased localized blood flow to particular areas of the brain hyperemia, and the correlation of hyperemia to local brain activity is termed functional hyperemia. This increase in blood is not due to rising metabolic demands of the cell. We can see how this makes sense since the metabolic cycle of a cell would only increase activity over a longer period of time than it takes to fire the action potential. In order words, if the increase in blood flow was to provide more support for the cell to produce neurotransmitter, which is made in the cell body the slowly transported to the terminal bouton where it can then be released with the occurrence of an action potential, increase in activity would be a delayed response to hyperemia. However, what we see instead is a nearly instantaneous reaction of the neurons/glial cells to the local hyperemia. In fact, part of Moore’s talk discussed a cell that was imaged in his lab, which wraps around the blood vessel. Therefore, when the blood vessel dilates, it is proposed that mechanoreceptoros on the particular neuron cause immediate depolarization. This would theoretically relay information about local hyperemia to other cells. However, a cell need not be wrapped around the blood vessel in order to be affected by local hyperemia. As Moore himself stated, no soma in the brain is more than 30 microns away from a blood vessel. This is such a close proximity that it cannot be imaged with traditional techniques. The technique which allowed for this type of imaging is known as optogenetics, in which a light-sensitive protein is incorporated into the anatomy of genetically altered mice. This protein depolarizes the cells in response to light stimulus.
The greatest lesson to be learned through Moore’s research is that functional hyperemia, while poorly correlated with metabolic demands, is highly correlated with information processing. In layman terms: where the brain is firing is where the blood is going. It is important to note that correlation is not causation; though it may be that the blood flow increases the activity of the neurons/glial cells, it may also be likely that the neurons or astrocytes drive blood flow as a neuromodulator. One proposed mechanisms of interaction between the neural cells/glial cells and blood flow is via the neuromodulator nitric oxide gas, which might easily pass through the blood-brain barrier. Either way, blood acts as a highway to quickly communicate information long distances within the brain and throughout the body.
Chris Moore’s talk brings up many interesting points about how we see communication in the brain. It is important to have speakers like him come and talk at Trinity, as this type of research challenges our current view and context of neuroscience. That said, there were some major points for improvement in the lecture he presented. Moore seemed to jump from topic to topic, from experiment to experiment, glossing over the methods sections or mentioning it as an afterthought. This caused his lecture to lack flow and cohesion. Instead of using his slides to support the main theme of the talk, each slide stood independently of the others. This may have caused confusion for those in the audience. Perhaps the comprehensive lecture given before the common hour talk, which I was unable to attend, was better setup and more well-taught. However the common hour lectures are open to the entire campus and a non-science major who had not read his article would be like a fish out of water if they had only attended the common hour talk. Keeping these points in mind, if these lecture issues could be remedied, I would recommend Chris Moore to come and lecture at Trinity again.
Reference:
Moore, Christopher I., and Rosa Cao. “The Hemo-Neural Hypothesis: On The Role of Blood Flow in Information Processing.” Journal of Neurophysiology 99 (2008): 2035-047. Web

Julianna Maisano

30 September 2015
Douglas Coutler’s Science for the Greater Good Lecture Reflection
On Thursday, September 24, 2015, Trinity College alumnus Douglas Coutler ’80, kicked off the College’s Science for the Greater Good lecture series. A Professor of Pediatrics, and a member of the Department of Neuroscience at the University of Pennsylvania, Dr. Coutler discussed the research that he as conducted on epilepsy. Dr. Coutler’s research centers on better understanding the cellular and molecular mechanisms that enable epilepsy to develop (University of Pennsylvania, 2015). To begin his lecture, Dr. Coutler expressed that epilepsy simply does not derive from a single source, but rather many sources. In order to understand how the underlying mechanisms for epileptic seizure and the distinct types of stimuli needed to generate these seizures, Dr. Coutler uses many different physiological, functional imaging, anatomical, and molecular techniques to address this disorder (University of Pennsylvania, 2015).
Epilepsy is one of the most common neurological disorders, with the most common symptom presented as a seizure. As the uniform component of epilepsy, seizures occur when there is an abnormal amount of synchronous neuronal activity within the brain. a seizure presents itself externally as numerous uncontrolled jerking movements, as a result of the excessive amounts of synchronous activity (Fisher et al., 2005). Dr. Coutler expressed that while there is no known treatment for the underlying disorder, it is known that the hippocampus is a structure involved in epilepsy. Subsequently, it is also known that those who suffer from epilepsy are at an increased risk for unexpected death.
Through his research on the disorder, Dr. Coutler has discovered that the dentate gyrus plays a key role in understating the mechanisms of epilepsy. By examining activity in the dentate gyrus during a seizure, we are able to assimilate, break down, and discover the network of structures that are involved during a seizure. Dr. Coutler found that during an epileptic seizure, the dentate gyrus amplifies neuronal activity into the hippocampus which is not suppose to be there. Subsequently, the dentate gyrus circuit within the hippocampus falls when apart when someone experiences epilepsy early on in their lives (Coutler, 2015).
While not enough is known about the development of epilepsy to single out a certain trigger stimulus, functional studies of the disorder are necessary in order to understand how the entire epileptic system works. Because neurons do not work in isolation, activity of all parts of the brain during an epileptic seizure must be assessed. Neuronal circuit dynamics can be analyzed using MRI, EEG, and MEG imaging, however MCI and VSD imaging are more effective as they are able detect activity at the smallest cellular level. To conclude his lecture, Dr. Coutler expressed gratitude towards about the benefits of being a Trinity College alumnus. He encouraged the audience to take classes outside of their comfort zone, pursue their interests, and when conducting scientific research to look for rigor and keep a broad approach.

References

Douglas, C. (2015, September 24). Epilepsy. Lecture presented at Science for the Greater Good
Lecture Series.

Fisher, R., Boas, W., Blume, W., Elger, C., Genton, P., Lee, P., & Engel,
J. (2005). Epileptic Seizures and Epilepsy: Definitions Proposed by the International League Against Epilepsy (ILAE) and the International Bureau for Epilepsy (IBE). Epilepsia, 46(4), 470-472.

University of Pennsylvania. (2015). Douglas A. Coulter || Department of Neuroscience || School
of Medicine || University of Pennsylvania. Retrieved from, http://www.med.upenn.edu/apps/faculty/index.php/g309/p10704

After a semester of work, today I said goodbye to a great organization.

This semester, I organized a 400-person annual fundraising event that saw a 30% rise in revenue for an amazing nonprofit.  I have had a great time with BIAC, and I can’t wait for the chance to speak of them fondly in the future!

Thank you, Professor Raskin, for facilitating this experience.  It has opened my eyes to all the wonderful work that BIAC does, the hard work that goes on behind the scenes, and the great people who are involved in brain injury prevention, awareness, and rehabilitation in Connecticut.  I can now say that I know a decent amount about how small nonprofits work and how I can contribute to their goals.

We are now working on post-walk tasks, which mostly revolve around sending out thank-you postcards and letters.

Last week, I mostly worked on the post cards.  It was quite frustrating to redesign the post card five times, as I mentioned in the most recent lab meeting, but the energy is necessary in order to portray the organization in a favorable light.  It’s all aesthetic and marketing.

This week, I worked on the thank-you letters.  In the process, I learned how to do mail merge, which is quite tedious but also quite helpful.  Eric, our temporary tech person, sat down with me and colorfully explain how to use mail merge and why it works like it does, which was so helpful!

The next thank-you task is for our volunteers.  Christina and I have done some brainstorming, but it’ll need a little more work.  We’re going for a “cutesy” theme, hoping to put a puppy on the card or something like it.

As for my final project, I have contacted Hartford Hospital to see if they are open to sharing (anonymous) data in regards to how their patients acquire brain injuries.  We’ll see how that turns out.

Chloe White
Professor Bell Lecture
11.7.2015 !
Stress on the Brain: The HPA Axis and Behavior !
Margaret Bell, a researcher on Neuropsychology and Biological Psychology at the
University of Texas at Austin, came to Trinity to give a lecture titled “Stress on the Brain: The
HPA Axis and Behavior.” Since she may potentially be a professor at Trinity in upcoming years,
Ms. Bell gave this lecture in the way that she would teach a class, so students could get a taste of
her teaching style. In her lecture, she diagrammed two main points: how the HPA axis is
organized, and what negative feedback is/how it works with the HPA axis.
In order to address the HPA system, we first need to talk about the basic endocrine system
in the human body. There are two main types of hormones that act in the human body: protein
hormones and steroid hormones. Steroid hormones, made up of fatty substances such as lipids
and cholesterol, can move right through the phospholipid bilayer of a cell. Hormones that cannot
do this, such as protein hormones, must use membrane receptors in order to get inside of the cell,
and nuclear receptors to then get into the nucleus of that cell. These nuclear receptors activate
2nd messengers in the cell. The membrane receptors activate the creation of mRNA and can
change protein expression: basically, they can change gene expression. The changes that occur
from these two receptors combined cause changes in the brain and in behavior.
The HPA axis is a set of interactions, signals, and feedback systems between the
Hypothalamus, Pituitary gland, and Adrenal Cortex (hence the name HPA). The main function of
this axis controls the body’s reaction to stress, however it also influences processes such as
digestion and the immune system (functions that are influenced when the body goes through a
stress response). Each of the endocrine glands in the axis releases hormones and substances onto
the next. The hypothalamus releases Corticotropin Releasing Hormone (CRH) onto the Anterior
Pituitary, which then releases Adrenocorticotropic Hormone (ACTH) onto the Adrenal Cortex.
The Adrenal Cortex releases multiple glucocorticoid hormones (mostly cortisol) in response to
receiving the ACTH- however, these glucocorticoid hormones then act on the hypothalamus and
the pituitary in a negative feedback cycle.
A negative feedback cycle is often compared to a thermostat. A thermostat works because
it knows what it’s supposed to be at (set point), it senses the environment around it, and makes
changes to adjust to the environment. Our body works this way as well. When the Adrenal
Cortex receives ACTH from the pituitary, it starts producing cortisol. However, if it starts
receiving too much ACTH, the cortisol will start acting on both the hypothalamus and the
anterior pituitary, signaling them to stop. It does this by binding with receptors on these two
glands, which notifies them to stop producing CRH and ACTH.
Ms. Bell then had us do some problems in order to apply these theories on a real-life
study. The study concerned two different types of mother mice: High LG-ABN and Low LGABN.
High LG stands for High Licking/Grooming, meaning this mother paid a lot of attention to
her newborns and created a lot of space for them. On the other hand, Low LG means the
opposite: she didn’t pay a lot of attention to her newborns. The study was looking at how
offspring of these two different types of mothers would respond to stress. Overall, it was found
that offspring of High LG mothers responded to stress with less of a chemically-stressed
reaction, and they also returned to their baseline chemical levels quicker than Low LG offspring.

Chloe White
Walk for Thought Blog Post
11.3.2015 !
What did you learn about brain injury? !
When thinking about brain injury, I often think about people who have become severely
debilitated and who can no longer function or care for themselves. I believe that this image
readily comes to mind because this is often what is portrayed in the media. When reading the
news or watching TV, the stories that are most often published are the ones which have the most
horrific results. However, this year at the Brain Injury Alliance’s annual Walk for Thought I had a
very different experience.
At the Walk for Thought, there were two different T-Shirts being handed out: yellow and
orange. The yellow shirt stood for survivors, and the orange shirts were given to everybody else.
I was amazed at how many yellow shirts were given out. An overwhelming amount of survivors
came out to the walk, as well as family members, friends and caretakers. I was surprised that so
many of them seemed, for lack of a better word, normal. More than once I was surprised to be
handing a yellow shirt to someone who I had assumed was a caretaker. (Disclaimer: I am not
saying that although some survivors seemed “normal,” they are not dealing with debilitations
every day).
To sum up, what I really learned about brain injury is that it can present itself in so many
different ways. Throughout everyone who came through my pre-registration table, they all
seemed to have one thing in common: they had all outwardly accepted that their brain injury was
something they had to live with, and they were ready to both fight for and support others who
were in the same boat that they were

Lizzy Foley

11/2/15

Neuroscience Across The Curriculum

Young Blood for Old Brains” lecture by Tony Wyss-Coray, Ph.D.

Sitting in the Life Science’s Center, Tony Wyss-Coray listened patiently as my fellow students and I working in Professor Masino and Ruskin’s lab talked about our own research projects. He asked questions that were both scholarly and though provoking, as expected from as Professor at Stanford University. Right across from him sat his daughter, Livia Wyss, a junior neuroscience major who has been working with ketogentic diet and it’s effect on inflammation in rodent models. Wyss-Coray listened, enthusiastically, to his daughter speak before steering the conversation towards his own life as a scientist.

Wyss-Coray explained that in his home of Switzerland, he grew up fascinated by science, most specifically by plants. However, he realized at a young age that his interest in plants was more of a pastime than a potential career. Instead, Wyss-Coray was swayed to study immunology by a particularly captivating professor. In terms of our scientific understanding of immunology, Wyss-Coray could not have begun research at a more fascinating time than the AIDS pandemic, which was initially recognized in the early 1980s. In 1993, his research on HIV related dementia led him to American where worked at Scripps Research Institute and later Stanford University’s medical school where he works currently as a Professor of Neurology. Today he studies blood plasma and it’s role in Alzheimer’s disease, which he talked about during his lecture this past Tuesday.

Wyss-Coray began his talk by introducing a study of parabiosis in which the vascular system of an old mouse was surgically attached to that of a young mouse. The artificial joining allowed for the blood of the young mouse to flow to the old mouse and vice versa. Remarkably, it was found that the brain of the old mouse looked younger when exposed to the younger environment. In such context, the term younger is defined as the creation of new neurons, higher synaptic activity, higher levels of genes involved in memory, and less inflammation in the brain.

When applied to humans, the parabiotic experiment opened the doors for many other age related studies. Wyss-Coray stated that as human’s age neurodegeneration is inevitable. Yet, it seems that infusing the blood or cord plasma of young humans into older humans with Alzheimer’s disease helps temporarily rejuvenate the brain by increasing neurogenesis and synaptic plasticity most noticeably in the hippocampus, a region associated with learning and memory. It seems to Wyss-Coray such neural transformation is due to the growth factors within the young plasma.

The research suggests that the human brain at every age is malleable. Such idea is an optimistic concept as it suggests that certain parameters such as plasma growth factors can help improve cognitive ability and delay neural degeneration. Although Wyss-Coray recognizes that the currently fountain of youth concept is unattainable, his research suggests that there are potential ways to delay the process of neural degeneration and prolong cognitive youth even as you age. Overall, Wyss-Coray’s research is ground breaking as it provides a possible way to deal with pervasive degenerative diseases and improve the quality of life for many individuals.

Tommy Hum-Hyder

Neuroscience Across the Curriculum

Novermber 2, 2015

Young Blood for Old Brains

Last week, Dr. Wyss-Coray of the Stanford spoke to us about his recently published work in Nautre magazine that further explored past research revolving around the idea of parabiosis. Parabiosis techniques began with the surgical joining of old and young mice, and it was discovered that old muscle was able to be rejuvenated with attachment to the young mice. Subsequent studies were then able to determine that other tissues could achieve the same effect. Dr. Wyss-Coray then began thinking of applications of this parabiosis to aging. As we age, synapses prune, neurons die, and the stability of our genomes changes, as the ends of chromosomes shorted and methylation occurs. Given that blood connects all organs, Wyss-Coray and his team wanted to see how aging affected the brains without performing biopsies. To do this, he measured one hundred proteins of cellular language in an effort to find the signature of aging, or the correlates that commonly occur in aging mice. Among these correlates, were proteins associated with inflammation, such as CCL11 or Eotaxin. With this knowledge, the team then transferred plasma from young mice to old mice and found increased memory function and that some of the correlates of aging decreased, which seems to suggest that there is something about young blood that can lead to a decrease in aging. The experiment was then redone, but this time with human plasma into aged mice, that were specially made to accept human plasma. They were then able to note that the greatest changes were in levels of CAMIIK an and c-fos.

“As you grow, you learn more. Aging is not just decay…it’s growth. It’s more than the negative that you’re going to die, it’s also the positive that you understand that you’re going to die, and that you live a better life because of it.” –Morrie Schwartz

On Wednesday October 14^th Playhouse on Park brought to life once again the memoir Tuesdays with Morrie by Mitch Albom. I started off with a quote from the play because I found it enlightening that a man suffering from a disease that actually speeds up the decay of his own body could change his perspective and use the unfortunate events of life to better understand himself, the disease, and the purpose of life. Morrie Schwartz was a 78-year-old sociology professor at Brandeis University who was diagnosed with amyotrophic lateral sclerosis (ALS) during the summer of 1994. Commonly known as Lou Gehrig’s disease, nicknamed after one of baseball’s greatest, ALS is a progressive neurodegenerative disease that targets the nerve cells in the brain and spinal cord (“Amyotrophic Lateral Sclerosis (ALS) Fact Sheet”). Over time motor neurons in the body start to die and the brain’s ability to stimulate control of muscles is lost. Without this connection “sclerosis,” or hardening, of the muscles occur creating the inability to walk, speak, eat, and in Morrie Schwartz’s case eventually breathe. ALS is a debilitating disease that effects people of all race and ethic background and does not have a proven cause. It is the most common neuromuscular disease worldwide; however, there is still a copious amount of information about the disease that remains a mystery. Strides have been made in the past twenty years regarding ALS research identifying specific enzyme mutations associated with the disease. Due to the fact that the disease has been difficult to identify time has not been dedicated to intensively researching the disease until recently. People like Morrie Schwarts who use their own obstacles in life to help progress knowledge and spread awareness aid in the development of further research studies regarding ALS and hopefully one-day help pinpoint the cause and cure for the disease.

“Amyotrophic Lateral Sclerosis (ALS) Fact Sheet.” National Institute of Neurological Disorders and Stroke. National Institutes of Health, 18 Oct. 2015. Web. 25 Oct. 2015.

Elizabeth DiRico

Tuesdays with Morrie

Tuesdays with Morrie, the play adaptation Based on the true story of Morrie Schwartz is the story of a Brandies university professor of sociology dying of ALS and his relationship with a former student. As Morrie walks the finale bridge between life and death he shares life lessons with his student and consequently reconnects him with what is truly important in life. In fact, Morrie Schwartz shares his life lessons along with his dying process with the world through a series of interviews conducted by Ted Koppel.

On a deeper neurological level, the play illustrates the complexities and devastation inflicted by Amyotrophic Lateral Sclerosis more commonly known as ALS. ALS is characterized by the degradation of cells responsible for controlling voluntary movement, leading to paralysis and ultimately death. Thanks to recent campaigns such as the ALS ice bucket challenge, there is a high degree of public awareness surrounding this debilitating disease. Based on my comprehension of ALS on a cellular level I previously believed that I had a good understanding of the disease. However, witnessing Morrie’s battle first hand illustrated many facets that I had previously overlooked. Most notably, this was exemplified by Morries maintained mental capacity as his body deteriorated. This is one of the more gruesome aspects of the disease considering that ALS is a motor neuron disease it does not impair cognitive function. Instead it impends the mechanism responsible from sending signal from the brain to the muscles, inhibiting voluntary movement.

To date, mutations in 29 genes have been implicated in causing ALS, yet these mutations account for only one-third of total cases. A tremendous amount of research continues to be conducted to better understand ALS as well as prevent this devastating disease. Nearly twenty years after his death, Morrie’s story is still being told and he dose his part to spread awareness about ALS and continues to inspire his disciples to live a happy and meaningful life.