Carsten Lohan
On Tuesday December 1st, the Trinity Institute for Interdisciplinary Studies hosted a well attended lecture titled: Neuroscience and the Humanities. Three speakers each spoke on the notion of memory, and sought to clarify what current scientific knowledge of the brain could tell us about the study of the past. The first speaker, a Trinity professor of Psychology, Elizabeth Casserly, briefed the audience on the more concrete aspects of memory, and how it acts as a function of the brain. She discussed the notion of a concept network as it pertained to the linguistic label of the word ‘cat.’ While that label of ‘cat’ could trigger a concept network of other words or ideas related to a cat, professor Casserly could not remember the name of her grandparents cat, just that it was black in color, and agreeable. As she said this, I had recalled an instance from a week or so earlier where I attempted to draw a floorplan for home I lived in until I was six. Comparing my floorplan with those of other units in the building (from online for sale listings), I had done a very good job of representing the rooms and hallways of my childhood apartment. However, I could not remember the floor it was on for the life of me. This irked me to great avail, and it emphasised what Ms. Casserly had been saying when she mentioned the difference of how memory was encoded in the brain under normal circumstances, and how it was encoded as a ‘flashbulb’ memory. My own autobiographical ‘flashbulb’ memories made me certain of the placement of the dining room table, as I had severely cut myself on it one day as a young child running through the house.
The next speaker, Aaron Seider, a classics professor at Holy Cross gave an interesting viewpoint of memory from the classical greek and roman perspectives. Perhaps the most interesting facet of information I took away from Mr. Seider was his mention of the Roman lawyers and how they had to often remember important details of their cases without notes. They used the method of Loci, where one creates a memory palace and places objects in that space. Sure, I had heard of this practice before (even by name,) but I did not know those of ancient times practiced it. One thing that Seider did not particularly mention was the heavy dependence of oral history in these times, and it’s flawed interpretations (or reinterpretations) of the past.
Yet, I was delighted when Professor Evelien spoke next, with his frequent quotations from German philosopher, Walter Benjamin. Evelien quoted an important line from Benjamin, “Memory is not an instrument for surveying the past but it’s theater. It is the medium of past experience, just as the earth is the medium in which dead cities lie buried. He who seeks to approach his own buried past must conduct himself like a man digging.” While I fully embrace Benjamin’s notion, I simply can not trust memory as the foundation of history. To do so would be dishonest to the past. Memory, as science can tell us, is unreliable. This is a notion I struggle with as a History major. To trust someone’s recollection as fact can prove dangerous. This is why I often place less emphasis on autobiographies of historical figures written later in their life. What would our understanding of American slavery be if we solely relied on the oral testimonials given by former slaves during the 1930’s as part of the WPA Slave Narrative Project? Most of those interviewed were in their 80’s or 90’s at the time, and were only children when emancipated. Thus, it is the task of the historian not to leverage memory as fact, but rather to interpret it through the lens of the past.

Neuroscience and the Humanities
Meaghan Race

Amongst a panel of neuroscientists, psychologists, and humanitarians the topic of memory was dissected and analyzed in term of human nature and historical events. Professor Elizabeth Casserly started the conversation with a presentation on the “cognitive network” that makes up human memory. Memories are a series of snapshots encoded by the brain and placed in connecting super-ordinate categories in a person’s network of memory. Episodic memory, or an instant in time that one is remembering relative to a cue word or concept, was a key focus in the presentation due to the fact that it is highly distributed. Sensory areas and language areas of the brain can trigger memories and stimulate emotional responses. Remembering something is reconstructing an experience using many simultaneous sources such as a person’s current state of mind, recent states, previous recall, and in-network links. Due to these various contributing factors memories tend to be highly inaccurate. Even so, people put very high trust in their own memories which creates a mismatch between metacognition and reality.
Aaron M. Seider, professor at the College of the Holy Cross, discussed how in ancient Rome it was perceived that people would store their memories in their “memory palace” where they could later go back and recall the event perfectly. He pointed out how Virgil’s quote about 9/11 reflected this way of thinking in the statement, “No day shall erase you from the memory of time.” The Roman way of thinking suggested that memories are concrete and cannot be influenced or changed over time, which we now know is an inaccurate assumption.
Lastly, memory was discussed through experiences documented by individuals in exile. In Benjamin’s Berlin Childhood, he compares the retrieval of memories to an archeological dig. Memories are as incomplete as the specimen that archeologists discover, the more the archeologists explore the area of a certain specimen the more they find. This fact parallels the retrieval of memories; the more an individual investigates a thought the more reconstruction of a memory occurs. Benjamin and many others realize how memory is a work in progress and that reconnection and comprehension occurs over time and tend to be influenced by outside factors.

Lizzy Foley
COLL-118
Neuroscience and the Humanities

During common hour on December 1st, Trinity Institute for Interdisciplinary Studies (TIIS) featured a panel discussion on Neuroscience and the Humanities. The panel included three professors: Aaron Seider, Ph.D. from the Classics Department at College of the Holy Cross, Johannes Evelein, Ph.D. from the Language and Culture Studies at Trinity College, and Elizabeth Casserly, Ph.D. from the Psychology Department and Neuroscience program at Trinity College. Ultimately, each professor presented on the relevance and function of memories within their respective discipline. Then, together they answered questions from the audience.
Professor Casserly began first, describing the concepts what it means to “know” and “remember” something. She suggested that the act of knowing is results of the formation of a neural network, what we consider a memory. Thus, the act of remembering is the activation of such network. She then mentioned that as we age, and our own self-concept as well as ideas that make up our neural network change, then our memories will change accordingly. This exposes the ideas of memory inaccuracy and inherent error in our own process of metacognition. Specifically, Professor Casserly mentioned a longitudinal study that recorded individuals recount of the terrorist attacks on 9/11, just after the events occurred. Researchers then followed up with the same subjects years later asking for them to recall what they remember. It was found that across the board, there were major inconsistencies between what was originally reported and what subjects later described, ultimately supporting the idea that changes of self-concept will affect the retrieval of a memory.
Another interesting study mentioned by Professor Casserly was concentrated on memory in terms of both recall and recognition of the apple logo. Interestingly enough, the study finding suggests that participants were overconfident in their ability to free draw and point out the correct apple logo. The results indicate that such overconfidence could be reduced if the participants attempted to draw or point out the apple logo before making judgments about their ability to do so.
Next, visiting Professor Seider spoke on the importance of memory to the Roman people. Just like Professor Casserly, he mentioned that memories change with time. He described that buildings were once inscribed with the names of the financial contributor. He recounted an instance of a particular building being burnt to the ground and reconstructed years later with the same inscription. To the romans, these buildings represented a resolute and solid form of memory. Professor Seider used this anecdote as a method to illustrate the inevitable nature of memory inaccuracy, because if a building was destroyed and remade it is inherently changed, therefore the inscription with the financial contributor’s name is effectively an inaccurate memory.
Finally, Professor Evelein talked about the documented memories of various European exiles. He described the emotions such as isolation and regret that may affect a memory when thought of retrospectively. This was in line with the previous talks of Professor Casserly and Professor Seider that touched upon the nature of memory reconstruction when the individual themselves has a changed in the way they view themselves. Professor Evelein left the audience with an quote by Salmon Rushdie which was a great example of the intersection of multiple disciplines: neuroscience, history, and literature: “Memory has its own special kind. It selects, eliminates, alters, exaggerates, minimizes, glorifies, and vilifies also; but in the end it creates its own reality, its heterogeneous but usually coherent version of events; and no sane human being ever trusts someone else’s version more than his own.”
Attending this panel left me with a strong sense of the importance of interdisciplinary studies. Concepts such as memory are so vast that they must be considered through the eyes of multiple disciplines in order to gain a true understanding. Ultimately, being exposed to the intellectual diversity of different disciplines opens the door for increased capacity to make larger connections and problem solve. After attending the talk during common hour, I believe that panels such as neuroscience and the humanities should be held much more frequently.

Elizabeth DiRico
COLL-118
December 6th, 2015
The Complexities of Memory
In order to accurately define a concept as immense and complex as memory, there are many compounding aspects that must be understood. This was the idea behind the memory panel, an interdisciplinary approach at defining the physiological, historical and literary spheres of memory in order to better understand memory as a whole.
First, Professor of psychology Elizabeth D. Casserly began by defining long term memory as a network on interconnected pictures, experiences, and associated concepts. Although memory is stored in and often associated with the hippocampus, memory lives throughout the brain, and therefore memory in robust. To illustrate, the sensory receptor portion of brain can detect a smell and can trigger memories of past experiences of that smell as well as associated images. Memory retrieval is equally as complicated and is influenced by your current state for example you remember the dentist better when your lying down because it triggers the memory of lying down in the dentists chair. Additionally, Memory is also shaped by your current mental state, that is to say if your in a bad mood your more likely to remember something in a negative light, which could differ from your actually mental perception at the time on the event. However memory is often unreliable because we misconstrue information but store it all the same rendering the human mind incapable of differentiation false perception from reality . This was illustrated in a study called The Apple of The Minds Eye where only 1 out of 85 participants were able to correctly re-create the apple logo despite all 85 participants thinking they knew it.
Aaron Seider, Ph.D. professor of history at the college of the Holy Cross looked at how the ancient Greeks view memory as it was accounted in ancient archives. In the ancient story, a man is attending a celebration but when he steps outside the building housing the celebration collapses. In order to recount who was inside, he describes closing his eyes and visually recreating the celebration in his mind, he is then able to walk around and see the faces of those lost in the disaster. This story is a representation of the way ancient Romans perceived memory. This idea of being able to visually recreate a scene and tap into the special memory region in the original memory palace and continues to influence metacognition.
Similarly, Dario A Euraque also discussed how time and space tied into memory when he presented the literary context of memory thought the writing of historians during the time of Nazi Germany. The historians recounted to horror of the past but were unable to act to change their future. This concept ties together the fluidity of historical events and memory as the medium of past experience that dictates the direction of the future and is anchored in the present.
Overall the memory panel broadened my perception of my own metacognition by deepening my understanding of the interworking of memory. Memory is an intricate tapestry weaving together experiences, emotions and perceptions. To truly grasp memory we must view it in its many relevant contexts and not just from a biological standpoint.

From the Gene to the Clinic
Khaoula Ben Haj Frej
Dr. Douglas Macdonald ’89

Who wouldn’t want to be able to find the cure for Huntington’s Disease? Dr. Douglas Macdonald, a Trinity alum, is a research who claims to be on the road towards realizing this goal. In his lecture “From the Gene to the Clinic,” he began by showing images of a brain with and without Huntington’s disease, showing a loss of brain tissue with the progression of the disease. While everyone loses brain matter with the years, brain neurons are lost at a much faster rate in patients. He related his studies and general neuroscience to the subject of Michelangelo’s Sistine Chapel, where a figure encased in what seems to be a brain bestows knowledge on a man directly below him.
According to the speaker, Huntington’s disease is an inheritable neurodegenerative and peripheral disease rampant in families, as only a single chromosome with the disease is needed to have it. Neurodegenerative diseases involve the loss of “specific neural populations”(Sajuan and Bates, 2015); according to Dr. Macdonald, this loss is characterized by increased ventricular space in people with Huntington’s Disease. Furthermore, regions in the brain affected by neuon degeneration are parts of the corpus striatum, cortical pyramd, motor, frontal, and occipital cortices, and the hypothalamus (Sanjuan and Bates, 2015). The disease is also late onset, impacting those in their early 40’s, so those who have it have often already had children who have a 50% chance of also having the disease, discovered serendipitous. In fact, it is rampant in Lake Maracaibo, in Venezuela, where thousands of people have the disease. Detecting the disease, often by detecting the protein to which it is attributed, can be incredibly difficult to diagnose in vivo (Chase, 2015). Dr. Macdonald suggests a “disease modification” approach to fight the disease (Sanjuan and Bates, 2015).
Some challenges of this research, includes questions like “What to target” so that knockdown is sufficient, “where to treat” in the brain, “How much to suppress” so that minimum suppression can occur, and finally “when to treat” for optimal results. The answer to that last question is probably, “as early as possible.” Today, there are no curing therapies for Huntington’s disease. Currently, many therapies are symptomatic intervention, attempting to reduce or cure symptoms. Others are disease modifying, where the disease is treated very early on, delaying the onset of symptoms.
Dr. Macdonald’s research is currently attempting to combine pharmacology and therapy that cure the disease itself. The cause of the disease is known; all that is left is preventing its onset. From the gene to the protein, you can intervene at different steps, like transcription, translation, and clearance. Current, pharmaceutical and biotechnology companies work with the clinic to lower or suppress Huntington’s gene expression in brains with the disease. So far, HTT ASO’s have shown reversal and sustained beneficial effects in BACHD mice, or those with the disease. When it comes to drugs, the location of the drug’s introduction is incredibly important. For example, in the NHP striatum in the brain, AAV2-HD5 can lower Huntington protein, reducing expression in that area. Thus Huntington’s was knocked down, without also killing the neurons. Right now, PET tracers are also being considered as biomarkers for the disease, thanks to clinical data with mice.

Lizzy Foley
COLL-118

“From the Gene to the Clinic: Developing Therapies to Modify the Course of Huntington’s disease”

On November 19, Douglass Macdonald, class of 1989, delivered a speech as part of the Science for the Greater Good series. Macdonald began his talk with a brief overview of Trinity experience, speaking fondly about his time as chemistry major. He then gave a brief overview of his life after Trinity, which includes laboratory research alongside Dr. Bruce Merrifield, leading to the development of a novel peptide antagonist of the glucagon receptor. Macdonald then continued on to earn a Ph.D. in pharmacology and experimental therapeutics from the Boston University School of Medicine. Currently, however, Macdonald serves as the Director of Drug Discovery and Development at the CHDI Foundation, which he described as a not-for-profit biopharmaceutical company with a concentration on drug advancement for Huntington’s disease.
Macdonald focused the majority of his talk on Huntington’s disease and his goal to develop effective treatments for the disorder, which is a dominantly inherited neurodegenerative disorder, presently having a prevalence of over 30,000 cases in the united states alone. In addition to the specific mechanism involved in Huntington’s, Macdonald touched upon the manifestation of further disorders as a result of the disease. Such disorders involve an individual’s movement, cognition, and emotional well-being. Fortunately, a major breakthrough has been made – the identification of the polyglutamine repeat in the huntingtin (HTT) gene as the cause of the disorder. Ultimately, it was mentioned that the CHDI Foundation has created a biomarker that has been successful for measuring such pathogenic mutation in the cerebral spinal fluid of individuals with Huntington’s disease. This is extremely beneficial for people who carry such mutation but have not yet started to exhibit the typical Huntington’s symptoms. Macdonald suggested that his goal is to develop therapies for Huntington’s that decrease the amount of mutated protein that is generated in the brains of these patients. By and large, his objective is to use such biomarker to measure treatment efficacy.
Macdonald is an excellent example of a Trinity graduate who joins discovery, development, and neuroscience research, in order to improve the quality of life for individuals. I found it inspiring to listen to a professional who is interested not only in identifying ways to better the world, but setting these ideas in motion. Later that night, after his talk, Macdonald was present at the National honor society (Nu Rho Psi) induction ceremony. Following the delivery of a short speech regarding his passion for neuroscience, Macdonald was inducted into the society that was established in 2006. As a student present, it was absolutely astonishing to be induction alongside such a well-established and influential professional.

Julianna Maisano
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Neuroscience Across the Curriculum
1 December 2015
Douglas MacDonald’s Lecture, “From the Gene to the Clinic: Developing Therapies to Modify the Course of Huntington’s Disease”
On Thursday, November 19, 2015, Trinity College Alumnus Dr. Douglas MacDonald ’89, concluded the Science for the Greater Good lecture series with his lecture entitled, “From the Gene to the Clinic: Developing Therapies to Modify the Course of Huntington’s Disease”. As the Director of Drug Discovery at CHDI Foundation, Dr. MacDonald and his team are eager to develop drugs that will slow the progression of Huntington’s disease and to provide meaningful clinical benefits to Huntington’s patients as quickly as possible (CHDI Foundation, 2015).
Huntington’s disease can be defined as a neurodegenerative disease that impacts everyday muscle movements. The disease manifests from genetics and is found to run rampant within a family. An individual who suffers from Huntington’s disease typically loses brain matter around the brain’s lateral ventricles. While brain scans make it seem as if the ventricles are enlarged, the brain matter surrounding the ventricles are actually shrinking year after year. Symptoms include but are not limited to involuntary movements, difficulty walking, and slurred speech. Subsequently, many Huntington’s disease patients also experience other comorbidities such as psychiatric disorders (depression or mood swings) and cognitive disorders (slow processing).
It is known that Huntington’s disease is able to be treated in the pre-manifest stage. An autosomal dominant disease, scientist’s use genetics to the to explore the causes of and treatments for the disease. To do this, Dr. MacDonald analyzed the CAG codon within one genome to look for molecular codon mutations. Additionally, the team use biomarkers to identify and validate causes of Huntington’s disease by through PET imaging, quantitative EEGs, and by analyzing the cerebrospinal fluid of patients. Dr. MacDonald’s strategy to develop a treatment for the disease includes lowering the levels of huntingtin (HTT) gene within the brain and by modulating the key mechanisms of huntingtin via mouse models.
Ultimately, Dr. MacDonald and his team are eager to look for different ways to lower huntingtin by targeting specific known neural structures of the disease, suppressing the gene, treating patients, and intervening with the overall downfalls of the disease. Dr. MacDonald and the CHDI Foundation believe that a treatment will be found for Huntington’s disease patients, however, a lot of collaboration will be needed on order to do so.

References
CHDI Foundation. (2015). Retrieved, from http://chdifoundation.org/about-us/

MacDonald, D. (2015, November 19). From the Gene to the Clinic: Developing Therapies to
Modify the Course of Huntington’s Disease. Lecture presented at Science for the Greater
Good Lecture Series.

Andrew Hatch

Neuroscience Across the Curriculum
22 November 2015
Huntington’s Talk
In his talk about Huntington’s, Doug McDonald Spoke about the complicated path he took on his way to become the director of drug development at his pharmaceutical firm CHOI. Huntington’s is a common neurodegenerative brain disease for which little can be done. Since diagnosis comes late, after 50 percent of the striatal neurons have died off, treatment is focused on minimizing symptoms, rather than attempting to reverse the condition. Huntington’s is caused by the enlargement of ventricles, resulting in significant decreases in cognitive functioning. Huntington’s is a disease about 1 in 10,000 individuals will develop in the United States.
First observed by Dr. Huntington in the early 1900’s, the disease bearing his name is devastating in part by the difficultly to observe the onset. Typically, Huntington’s develops in individuals around 40 years old, and over the course of years, slowly kills off cells throughout the brain, with a specific focus on the neurons comprising the striatum. Over the course of time, patients with Huntington’s lose their ability to speak and movement becomes decreased and more uncoordinated. Huntington’s has a genetic basis, where it has been observed to be a recessive allele.
The focus of Dr. McDonald’s work is to focus on early, custom tailored treatments delivered in a “gene to the clinic” fashion. Huntington’s is difficult to treat, as it is but one way to help increase success rates is to treat both early and to tailor treatment of individual patients to their specific genetic makeup. Each persons Huntington’s might be a little bit different, therefore it follows that the best treatments are one focusing on individual treatments. Modern medicine has long tried to move to this methodology of treatment but patient access, particularly costs, make this near impossible, presently.
Dr. McDonald was a graduate of Trinity. He pursued his research at Rockefeller University. There he worked in the lab of Professor Merrifeid, who in 1984 won the Nobel prince for his research on the topic. He left and went to Medical School at Boston University where he pursued his joint MD/PhD. There he got introduced to working for major drug companies when he accepted a position working for Pfizer while still in school. The introduction to industry shifted his focus away from research and into the world of drug development.

Walk for Thought Blog

The Brain Injury Alliance of Connecticut is an organization that I hold close to my heart. I have had the opportunity to work with them on multiple events over the past year, such as the Valentine’s Day Dance and Healthy Living Retreat, and this past week I volunteered at their 11th annual Walk for Thought fundraising event. Events such as Walk for Thought are highly impactful for the brain injury community not just in a fundraising stand points but in recovery as well. The Brain Injury Alliance of Connecticut is the only organization in Connecticut that offers support to survivors and prevention education free of charge. Since brain injury is highly individualized and can happen to anyone it is beneficial to have access to a support system as a survivor. Acquired brain injury (ABI) is a commonly used umbrella term that describes brain injures that occur after birth but not related to degenerative disease or hereditary factors (“Brain Injury Basics”). Causes of ABI may include stroke, substance abuse, oxygen deprivation to the brain, and traumatic brain injury (TBI). Many of the individuals I encountered at the walk were survivors of traumatic brain injury, an injury acquired from a blow to the head or body that disrupts brain functioning (automobile accident, concussion, fall, etc). A large percent of the population has had or is still recovering from a TBI. Traumatic brain injury affects six times more people each year than spinal cord injuries, MS, HIV/AIDS, and breast cancer combined (“Brain Injury Basics”). There is also an increasing number in youths due to sports related concussions. Due to the fact that ABI’s are individualized there are many different recovery plans that can be pursued. There is not a set treatment plan for a brain injury; however, many patients receive rehabilitation in physical therapy, occupational therapy, speech therapy, psychology, physiatry, and social support (NINDS). Walk for Thought is one of the many events that provide social support for survivors while collecting funds to promote research being conducted to further understand the complexity of brain injury and develop better rehabilitation strategies. A big thank you is in store for the Brain Injury Alliance for all that they do for the survivors of brain injury and I am grateful to be a part of events like Walk for Thought which support the community.

Literature Cited

“Brain Injury Basics.” Brain Injury Alliance of Connecticut. Centers of Disease Control and Prevention, n.d. Web. 6 Nov. 2015.

“Traumatic Brain Injury Information Page.” National Institute of Neurological Disorders and Stroke. NINDS, 2 Nov. 2015. Web. 6 Nov. 2015.

Young Blood for Old Brains
Tony Wyss-Coray
Khaoula Ben Haj Frej
Last week, I attended Tony Wyss-Coray’s seminar, titled “Young Blood for Old Brains.” As though the title weren’t intriguing enough, Wyss-Coray, a Stanford School of Medicine professor, described his study of the use of the blood from young, healthy mice to cure Alzheimer’s in older mice. He spoke of the “Fountain of Youth,” a mythical fountain that revitalizes the elderly and frail who bathe in it and compared it to the current advancements being made in neuroscience. As the human mind ages, it is often plagued by degenerative diseases. He goes so far as to suggest his study’s capacity to reverse the effects of such impairments.
One such example of an attempt at rejuvenation is parabiosis, a method that surgically connects a young and old mouse, creating a shared internal environment in animals (Paul and Reddy, 2014). According to Wyss-Coray, in stem cell studies involving parabiosis, when the older animal was injured, the wound healed similarly as in the young mouse. Similar effects were seen in the pancreas, liver, heart, and most applicable here, the brain. Simply through exposure to a young environment, demyelination and vasculature in the brain can potentially be rejuvenated to the point where they mirror the younger model. After all, in parabiosis studies, anastomosis occurs, where blood is shared between the animals. Backing this up, Wyss-Coray performed an experiment where two old mice were joined by parabiosis and one old and one young mouse were joined and the pairs were compared; incredibly, only the older mouse connected to a younger specimen expressed increased synaptic plasticity (Villeda et al., 2014). Such a discovery could revolutionize the way age-related mental degeneration is viewed. Similarly, according to Wyss-Coray’ presentation, in a comparable but less drastic experiment, human plasma was administered to old mice caused a very distinct gene signal in the brain, strongly supporting the belief that blood content could impact the brain.
Of course, it would not be at all acceptable or very much useful to surgically attach two humans, but that does not mean that the early stages of this research cannot be applied to people with Alzheimer’s. The research is still in its fairly early stages and even Villeda et al., (2014) recognizes the multitude of questions that have yet to be answered, like what exactly the revitalizing factors in blood are or, even more broadly, if they would have the same impact in humans as in mice. Only after answering these questions and others would research be able to progress to the level of manufacturing a new subgroup drugs that could reverse Alzheimer’s, as opposed to those that thus far can only attempt to slow down its progression.
Works Cited
Paul, Steven, and Kiran Reddy. “Young Blood Rejuvenates Old Brains.” Nature
Medicine (2014): 582-83. Print.
Villeda, Saul A, Kristopher E Plambeck, Jinte Middeldorp, Joseph M Castellano, Kira I
Mosher, Jian Luo, Lucas K Smith, Gregor Bieri, Karin Lin, Daniela Berdnik,
Rafael Wabl, Joe Udeochu, Elizabeth G Wheatley, Bende Zou, Danielle A Simmons, Xinmin S Xie, Frank M Longo, and Tony Wyss-Coray. “Young Blood Reverses Age-Related Impairments in Cognitive Function and Synaptic Plasticity in Mice.” Nature America (2014): Print.