Elizabeth DiRico

To initiate Trinity College’s celebratory Twenty-Five years of Neuroscience series president Joanne Berger-Sweeney discussed the extensive research that she has conducted on Rett syndrome over the past 15 years. A pervasive neurodevelopment disorder categorized on the autism spectrum that plagues young girls. Symptoms of Rett syndrome typically appear around six months of age, including purposeless arm motions, difficulty with speech and slow cognitive development.

The cause of this disorder is a mutation to the MECP2 gene, a repressible gene that is responsible for producing and regulating MECP2 protein production as well as additional protein production. A random mutation in the MECP2 gene results in inappropriate regulation of protein synthesis, the operon has no ability to turn off DNA transcription and excessive protein is produced. There are significant repercussions for this single gene mutation because MECP2 is an essential protein in neurological development. The bodies inability to regulate gene production impairs the nerve cells and resonates in the form of debilitating neurological symptoms. Due to the genes location on the X chromosome, Rett syndrome is exclusively observed in girls. Girls second X chromosome is essential for compensating for the mutation, where as males do not have the second set of genes and are not able to survive such a crippling mutation.

President Berger-Sweeney first set out to investigate the effect of acetylcholine on MECP2 function. A major hurdle she encountered in her early experimental design was choosing a test subject that would closely mirror human symptoms. Her decision to use mice as a test models opposed to rats based on a more extensively sequenced genetic code, set her ahead of her time. The MECP2 mutant mice produced many symptoms of Rett patients right down to the stereotypical hand grabbing customary to young girls with Rett syndrome.

The effect of acetylcholine was investigated by feeding choline supplements to pregnant mice. The results demonstrated an overall improvement including increased brain volume, motor coordination, growth factors and neuronal health. In her published research, her finding showed that Choline supplements played a role in regulating DNA and histone methylation. She aimed to take this approach a step further my implementing chromatin remodeling drugs in place of supplements to better control DNA and histone methylation. Following the tremendously impressive results of the previous studies, President Berger-Sweeney began experimenting with Acetyl-L-Carnitine a drug she described as “choline on steroids”. Instead of a supplement, this drug was injected a does per day for thirty-six days. The results pertained form these experiments were even more impressive than the previous experiments. The overall health of mutant mice brain improved continuously up until day thirty, dendrites were examined and found to be longer and more extensively branched than before. The take away message was that the key to reversing the effects of Rett syndrome is early intervention.

Although President Berger-Sweeny is at the forefront in Rett syndrome research and has yielded impressive results, in terms of improving Rett syndrome, she will not be satisfied until she finds a cure. She spoke of feeling both an obligation and a connection to the girls who suffer from Rett syndrome. For her future research she hopes to explore the carbon metabolic cycle and believes that this process may play a role in the underlying mechanism of many developmental disorders, including Rett syndrome. Although President Berger-Sweeny has taken off her lab coat in order to step in to an administrative role, she fully intends to return to her research in some capacity.

Tommy Hum-Hyder

In her talk entitled, Of Mice and Men and Girls and Autism, President Berger-Sweeney reviewed her years of research looking at the relationship of the MeCP2 transcriptional regulatory protein on a mouse model of Rett Syndrome (Katz et al., 2012). The crux of her research was focused on the 1 in 10,000 females, who are born with this regressive developmental disorder. For the first 6-18 months post-natal, the child appears to develop normally; subsequently, muscle begins to atrophy, difficulty crawling or walking, as well as Autism Spectrum Disorder (ASD) type symptoms, such as reduced eye contact. (NINDS, 2015).

Prior to President Berger-Sweeney’s research, scientists believed that the cognitive and behavioral abnormalities associated with Rett Syndrome were due to deficits in the cholinergic system, which they believed was due to abnormalities in the MeCP2 protein, a transcriptional repressor protein. Berger-Sweeney and team decided to proceed with a mouse model despite many colleagues in other research fields using rat models. President Berger-Sweeney spoke of the importance of a good animal model and of the first questions that her research group asked, which included whether to model symptoms, genetics, neurochemical changes, or neuroanatomical changes. The group decided to proceed with a mouse model with MeCP2 gene knockouts.

After many years of research, the group found that the male mice with the gene knockout made to replicate Rett Syndrome experienced an increased in social behavior, which, at first, seemed to contradict typical Rett Syndrome symptoms. However, a literature review suggested that it is possible for Rett Syndrome human females to have increased social behavior, suggesting that the mouse model could be a good measure. The group then decided to look at ways in which they could take this effective genetic mouse model and try to improve symptoms. They began by using choline, a precursor molecule of the neurotransmitter acetylcholine. At muscle junctions, acetylcholine facilitates muscle contractions. Research has also suggested that it may be involved with awareness and attention, which could address cognitive Rett Syndrome symptoms. After positive results, the group decided to use an acetylated version of the l-carnitine molecule called acetyl-l-carnitine, which they gave to mice as a nutritional supplement. They then improved results relative to the choline treatments, but results also showed that the improvement only lasted until 30 days postnatal. This would lead to inconclusive results relevant to the treatment of Rett Syndrome in humans; however, due to few researchers interested in Rett Syndrome, any progress towards the eventual amelioration of symptoms can be considered a great advance in the study of females with Rett Syndrome.

On Thursday, Sept. 17, President Joanne Berger-Sweeney gave a lecture beginning a yearlong celebration of neuroscience within the Trinity community. Overseeing the festivities was neuroscience department chair Prof. Sarah Raskin. Students, faculty, and the Hartford community packed the Washington room last Thursday to listen to the president discuss her years of research on Rett Syndrome, a form of autism exclusive to girls.

The president’s lecture was segmented in two parts: The first, a general overview of Rett Syndrome, and the second being an in-depth accounting of the known genetic causes and possible treatments. Much of her research has been focused on trying to establish possible treatments for the condition as well as to recreate and test the work of others to help assess the validity of their research.

Throughout her talk, the president shared many personal anecdotes and continuously stressed persistence. She realated her experience of trying to gain the attention of a famed neuroscience researcher, which took her many phone calls. The President also playfully recounted an experience where her lab rats were sent from a colleague’s lab in Boston to her lab at Wellesley College via taxicab. On a more serious note, her research has revealed several causes of Rett Syndrome and identified several treatments. In her research, Dr. Berger-Sweeny has tested the effectiveness of her colleague’s treatments, though in several regrettable cases she found them to be ineffective. Fortunately, her joint research with a fellow colleague has produced and patented a compound they hope might be a viable treatment.

President Berger-Sweeney concluded her talk with some advice to budding young scientists; persist, ask questions, and ensure you have a strong support group. The president thanked her family for their tireless support of her as well as thanking her many colleagues in the scientific community, as well as her many undergraduate research assistants. President Berger-Sweeney’s lecture set the stage for a year which will feature a divers array of neuroscience related events, ranging from art and music, to scientific symposiums and guest lectures.

Amina Kureshi

On September 17th, our own President Berger-Sweeney gave a talk on the neuroscience research she has published. Rett Syndrome, which is on the Autism Spectrum Disorder, is a severe developmental disease which affects boys and girls alike. Rett syndrome is characterized by short term overconnectivity and long term underconnectivity of neurons. Unfortunately, boys with Rett Syndrome do not survive birth, so the disease is known to affect girls. It causes motor dysfunction as well as respiratory issues, which leads to a low survival rate after the age of thirty.

There is no known cause of Rett syndrome, so how do we give mice Rett syndrome so that we may study it further?  It was found that the Mecp2 gene is downregulated in about 95% of cases of Rett syndrome. Therefore, eliminating the Mecp2 gene in mice will be an electrical, biochemical, genetic, and neuroanatomical analog to the human condition, as genes regulate development from conception. So these mice which have the Mecp2 gene eliminated then have to be tested to determine how closely they model the disease in humans. Therefore, testing was done to determine the sociability, motor skills, respiratory ability, cognitive function, ect.. Once these mice were tested, and determined to be a viable analog to Rett syndrome, they were used to study treatments for Rett syndrome.

The Mecp2 protein is used to regulate transcription of genes by binding to the promoter region of the gene and recruiting other proteins to block transcription of the respective gene. Therefore, when the Mecp2 gene is not producing the Mecp2 protein, the gene that it normally blocks is upregulated. It is theorized that this is the cause of Rett syndrome.

Acetylcholine, which is a neurotransmitter used to communicate a signal from a neuron to a muscle can be upregulated by increasing its precursor, choline. Therefore, the research conducted in Prof. Berger-Sweeney’s lab used choline as a nutritional supplement in pregnant Mecp2 mice to determine its effectiveness in preventing the onset of symptoms, particularly the cognitive symptoms. It was found that the treatment did improve symptoms, but not for the entire lifespan of the mice born having had the nutritional supplement. New avenues for research are looking into the C1 metabolism pathway to improve acetylcholine function.

The president’s talk was well thought-out and proved her scientific “chops” to us undergraduate students. Indeed, she schooled us with questions about the byproducts of the Kreb’s cycle and other biochemical mechanisms. My impression is that President Berger-Sweeney would make a good Neuroscience professor not only in lecture, but also in laboratory research. If only she had a research lab at Trinity for us students to benefit from. Perhaps the most memorable part of her talk was a shared story of another fellow female neuroscientist who was her mentee. This woman wanted to start a family and in order to be a full time mom, she was seriously considering leaving the sciences as a profession. President Berger-Sweeney, in response to hearing this, told her to work in her lab, and eventually she rose the ranks to hold a prestigious position in the sciences. This message is especially important for the female science majors, myself included, as it gently reminds us and inspires us to live a full and complete life without having to sacrifice home life for career or vice-versa.

First off, an announcement: I found a food truck!  Julie was a little nervous, but it all worked out.

The thing I am seeing less success with is sponsorships.  I’m not sure if it has something to do with seeing my name instead of Christine’s, or if I am simply going about it in the wrong way (though I do copy Julie’s format each time I send out an email soliciting a sponsorship from a specific company).  It also could be that it’s simply a tougher task.  On the bright side, the new development director starts on October 1st, so communicating with potential sponsors with won’t be part of my job for much longer.

It feels as though I am making significant progress.  I don’t have the prior experience to judge where I am in the planning process as compared to where I should be, but it seems like things are moving along well.

It’s also easy to lose myself in the tasks and forget why I do this work.  At CASO today, someone new came in.   She has been concussed for almost five years.  As she was telling me about her struggles (and signing up for Team Trinity), I was reminded of the people I’m working for.  As I heal, it’s easy to lose touch with how difficult it used to be to even have a conversation with someone.  My meeting with this person helped put me back in touch with the struggles of a survivor.  I hope this humble reminder stays with me for awhile.

Few can deny that the producers at Pixar are capable of taking moviegoers on an emotional journey. Of the 15 Pixar films in the past 20 years, I can’t think of one that didn’t invoke several strong emotions, or a pull on my own heartstrings. They started two decades ago with Buzz and Woody in Toy Story, graduating to Nemo, WALL-E, Lightning McQueen, and most recently Riley of Inside Out.   The producers at Pixar certainly understand how to play to the audience’s emotions. Yet, Inside Out was different. The film was about emotions, and how they affected Riley in her tumultuous year that was compressed into 90 minutes. See, Inside Out was the first Pixar Film to make me think about what I was feeling as I was watching the movie. I cried when Bing Bong sacrificed himself so Joy could escape the abyss of the Memory Dump – but why was I crying? Was I crying because Pixar wanted me to cry, or simply because for a few moments I was transported to a more juvenile state where I could express my emotions freely? A week has passed since I saw the film, and I think I have finally realized why I was crying. The tears were the product of fear – a fear of forgetting those memories that I cherish, but are constantly being overwritten by newer memories. Perhaps this stems from a now deceased grandmother who had Alzheimer’s, and would constantly confuse me with my uncles, or worse, not even remember me at all. It was annoying at first, then terrifying, to have all these memories abandoned, forgotten and wiped. The visual depiction in the film was a strong one of bowling ball shaped ‘memories’ darkening and finally turning into dust. I could imagine this happening in the chasms of my own brain at an increasing rate – and the fear that comes along with it.

This realization brought about an internal dialogue on the differences between fear and anxiety. Was it anxiety or fear that drove my thoughts? There is a distinct difference, of fear being an emotional response to an implicit danger, and anxiety being the threat of a perceived danger. This I knew, but I believe the line between the two is not so sharp as some would like to believe. I will try to navigate the divide between fear and anxiety, however Inside Out allowed me to recognize the importance of all emotions – Joy, Sadness, Disgust, Fear and Anger.

As an older sister to a 7 and 12 year old, I am extremely familiar with animated movies, particularly those well loved Pixar and Disney films our society holds so dear. Last weekend, along with about two dozen other college students, I sat through (and enjoyed) Cinestudio’s showing of Inside Out and Professor Helt’s interpretation and analysis of the film.

The movie allows one a glimpse into the mind of a young girl and five of her six core emotions, Joy, Fear, Sadness, Anger, and Disgust, each in the form of a humanoid, three dimensional character “living” in her brain (with the final, non-personified emotion being surprise). Simply put, core emotions are those that are expressed universally, with culturally specific characteristics, with neurons firing, resulting in distinct, shared facial or audible reactions (Ekman). For example, any surprised person is likely to jump, gasp, and make a startled face, recognizable even in photos. In the movie, one is allowed the chance to directly visualize Riley’s exact feelings at a given moment through the actions of core emotions, which play bigger roles than most of the other characters. In reality, however, one cannot look into another person’s mind to ascertain their thoughts and must instead ascertain them otherwise, often using facial expressions to make such judgments. In the late 1970’s, researchers Ekman and Friesen came up with the Facial Action Coding System, which, as evidenced by the name, is the only method by which particular facial movements are scored. These recorded movements were then studied to come up with inferences directly relating to emotion and emotional expression. What they found was that all emotions, while they may or may not have a variety of sounds or actions associated with them, all have a distinct facial expression or set of facial muscle movements (Ekman). Your expression, therefore, is truly the most important indicator of how you feel at a given time.

Young Riley spend most of her life influenced by Joy, spending her time ice skating and having fun with her family and friends. However, as she turns 11, she hits the point in her life when such perpetual happiness no longer applies to such a degree, as is common at that time of pre-pubescence and end of childhood (Keltner and Ekman, 2015). Instead, the other core emotions begin scramble for control, to such extremes, that the young character experiences a numbness and emotionless dip mirroring that of depression.

Professor Helt claims that, just as in the movie, we all do tend to have a primary or dominant core emotions, though probably not the over-simplified degree expressed by the characters. For example, at the very beginning of the movie, Riley’s dominant emotion was joy, while her father’s was anger and her mother’s sadness. In reality, most people would also identify with a single emotion, as well, with the majority claiming joy to be theirs. Life changes, like Riley’s family’s move, can result in a sudden shift in emotional stability, sometimes even altering which core emotion dominates the conscious.

Riley’s emotional evolution is heavily based on an increase of Sadness’s influence, rather than simply a drop in Joy’s. It’s not as though a switch flicks in Riley’s mind and she’s automatically painfully desolate; rather, a series of unlucky and unforeseen losses allow Sadness to take control, in minute measures. However, both Professor Helt and Keltner and Ekman’s article agree that the movie’s portrayal of this Sadenss is somewhat inaccurate as the character’s depiction is a little too extreme, with features such as sluggishness and extreme pessimism mirroring attributes more akin to depression. Regardless of how it’s portrayed, the movie’s message is clear; the expression of sadness is necessary and can lead to happiness eventually, once the emotion has been properly processed.

After all, a single emotion is not enough for a functional, realistic life; they must all be felt for one to be considered “healthy.” This validation of sadness as a natural emotion and precursor to happiness, however, isn’t exactly reinforced by our society, which supports false optimism far more, leading to people feeling the need to apologize for sadness and thus numb themselves to avoid expressing or even feeling it at all. However, numbing negativity also numbs happiness, which as seen in Riely’s case, leads to a squelching of emotions and plummet into depression, where emotions have less of an effect and one can slowly lose interest in the things they love, resulting in a single dimensional personality. Though it seems counterintuitive, the happiest people are those who allow themselves to feel every emotion, including the difficult ones.

Emotions are the basis for people’s personality, memories, and the general autonomic expression. They are all equally important to ensuring an individual’s mental health and stability, regardless of whether they are considered to be “positive” or “negative” emotions.

“Happiness is a choice”. It’s a phrase that mom and dad would utter again and again as I toiled through my angst filled years. But did I really have a choice? Was it up to me? For Riley, the protagonist of the film Inside Out, the delegation of emotion was far beyond her control. In fact, the catalyst for Riley’s emotions comes from Joy, the physical representation of the emotion happiness. The people who inhabit Riley’s brain and control her emotions and memories are the characters: Anger, Fear, Sadness, Disgust, and Joy. These characters emulate the emotion that their names would suggest, and with Joy at the helm, the team does their best to guide Riley through life.

So, was it up to me? Was it up to Riley? Do we really have complete control over our own emotions? As professor Molly Helt, and others, would explain during the discussion that followed the film, the answer is not quite black and white. Through the pioneering work of Dr. Paul Ekman and many others it has been found that our emotions, which are largely defined by our facial expressions, provide the basis for our perception of the world. For example, if we are angry we are most likely to nitpick and find qualms with any incoming situation. Conversely, if we are happy we are more likely to find the upside in our life. However, emotions do not only affect our perception and interpretation of our surroundings. Ones interpretations of memories can be largely based off the emotions that you feel while you are recalling the events.

At its core the film centers around Riley’s struggle with her transition to a new city. She fights her way through her first days of school, her first hockey tryouts, and the loss of old friends. All the while Riley feels immense pressure to keep her head up, adapt, and enjoy her new home. However, all Riley wants to do is go home. She pressures herself to make the choice to be happy, even though straying from her emotions worsens her situation. It is not until Riley embraces her underlying sadness that she is able to start her progress towards happiness. The film stresses the importance of how our emotions, especially sadness, hold the key to moving towards something better, something positive. Ultimately, it is Riley’s sadness that brings her the greatest joy.

Throughout the movie Inside Out, five out six of the commonly accepted universal
emotions are personified within the brain of a little girl, Riley. These five emotions are Joy,
Anger, Sadness, Disgust and Fear (the 6th emotion that was left out was Surprise). In Riley’s brain, the emotion that often seems to control her life is Joy. When we get a quick glimpse inside of the brain of Riley’s mother, it appears that Sadness is her main emotion. For Riley’s father, it’s Anger. Until our discussion after the movie, I didn’t think much of this detail- it seemed to me that the directors of the movie were just trying to mix up the characters so they weren’t all the same. However, during our discussion I learned that for a lot of people, there is one emotion that dominates them. The more I thought about this, the more sense it made. There are clearly people who get angry easier and more often than others, as well as people who seem overly cautious or who become disgusted easily. I believe that if I had a control board in my head similar to the one in the movie, Joy would be dominating it. When we discussed the dominant emotions of the parents, another interesting detail came up: as they age, women’s dominant emotion often becomes sadness, and males often become anger. When thinking about this detail while looking
at Riley’s life, the character Sadness definitely inherited a larger role as the movie progressed. While Joy seemed to run most of Riley’s childhood, she and Sadness started running Riley’s adolescent years together. If Disney and Pixar created another Inside Out movie about Riley as an older woman, would we see that her dominant emotion had completely turned to Sadness? Although there were a lot of small details throughout the movie that resonated true to me, I can only hope that this is not one of them. Although it can be easy to lose some of the fun-loving qualities of the childhood years that Joy brought to Riley, I refuse to give her up as my dominant emotion.

The story of Inside Out follows Riley and her family as they move their hometown in Minnesota to San Francisco. The Disney/Pixar animated movie follows five core emotions, Joy, Fear, Anger, Disgust, and, Sadness. As we follow Riley throughout her move, we become acquainted with each basic emotion and experience the complexities of emotions that Riley feels as a result of her move.

The beginning of the movie is largely dominated with Joy dictating most of the ‘controls’ in Riley’s command center. Joy prided herself on the four core memories that Riley has experienced, each of which was surrounded on a particular theme. These themes were family, trust, friendship, and hockey. These core memories focusing around times when Riley experienced immense joy, were on special display within the control center, which the movie portrayed as something akin to a marble. In the movie, memories were obtained through these marbles coming into the control center with a particular color: yellow denoting happiness, red – anger, green – disgust etc. For much of the movie, Riley’s memories were a single color – all memories were entirely dictated by one emotion. What I most enjoyed about Inside Out was the “long-term storage” area within Riley’s brain along with the commentary of the consolidation or removed of old memories. The movie accurately represented the ways in which memories are held within our brains. There are certain memories, referred to as flashbulb memories, which I found relevant to the movie’s usage of core memories. A flashbulb memory can be thought of a memory that is remembered very vividly or one that has significant emotional significance. Although most flashbulb memories are thought of with respect to negative feelings, it is possible to have positive flashbulb memories. Further, as Joy and Sadness were exploring Riley’s long term storage area, they stumbled across characters whose job was to dispose of memories that had lost their color, which signified that they were no longer memories that Riley had placed salience on. In many respects, this is accurate to our current understanding of the acquisition and holding of certain memories. We tend to hold on to memories with emotional significant or memories that we may need to recall, such as a birthday; whereas less important memories, such as someone’s telephone number, can be a memory for which salience can be easily lost.

As the movie concluded and the difficulties that Riley dealt with as a result of her move, we began to see a more mature Joy and Riley. Joy was able to learn that there is no scale for happiness without sadness and that a more complete individual is one who can appreciate the highs but power through the lows. Inside Out was able to beautifully capture not only the coming of age story or Riley but also the inherent struggles that we all go through in our lives, when we realize that the core memories that Joy had always thought were pure happiness was actually the result of another extreme emotion.