Synapses, Sonatas, and the Study Tour

Exposition (n.): 1) a passage or section which opens a movement of a musical piece; the first section of a classical sonata 2) a large public exhibition or festival

Welcome to my second blog! This week, I’ll be blogging about the course that took me to Stockholm: Molecular and Cellular Neuroscience — why I chose this course, what we’ve been doing so far, and of course, the amazing Study Tour (and one of the best weeks of my life).

I briefly touched on this in my last post, but I am fascinated by the potential of the connectome — a map of how the brain is wired — in aiding understanding of how different our brains are and in understanding how these differences affect our behavior. When I learned that researchers at Yale were able to identify a person just by the connectivity patterns of their brain, I was blown away.

The brain is a living network. It’s an architecture of neuronal cells and rapid-fire communication at junctions called synapses, complex electrical signals humming and firing every waking second to enable every second of our function as we know it. Any change (no matter how tiny) in the wiring system can be disastrous. The loss of synapses is a defining marker of Alzheimer’s; abnormal electrical spikes can signal seizures; slowed neuronal communication a telltale sign of multiple sclerosis. It is this delicate balance that makes comprehension of brain patterns and neuroimaging so crucial.

Neuroscience, as I learned then, offered the perfect crossroads where my love for biology and computer science intersected. Mapping neural networks is an extremely data-driven task built on clinical observations and records. The programming language MATLAB can aid in tasks from analyzing signal recordings of electrical activity to visualizing anatomical blood flow in the brain; new data formats such as the Scalable Open Network Architecture TemplAte (SONATA) have made it possible to model synapses with ease.

To this day, there has been no consensus on a singular, unified atlas or connectome — there are many out there at this time, each with their own perspectives and insights on mapping the brain. It’s difficult, though, to talk about disease or dysfunction if each atlas draws different boundaries for brain regions and circuits — we’re essentially left “without a common language.” At Yale, I conduct research in developing the Yale Brain Atlas, a project that seeks to map regions of the brain by structure and function in the hopes of eventually utilizing it as a guide for epilepsy treatment. But it’s just a small part of what’s out there — so when I saw that DIS was offering a class on exploring gene expression and proteins in the brain, led by two experts in the field studying the Human Protein Atlas — I was instantly intrigued.

Group reading with my classmates on three fascinating papers on neurodegenerative disease and memory. Later in the classroom, we shared the insights gleaned from these papers and added our critique to generate a lively discussion.

Under the guidance of Jan and Nick, the instructors of our course, we began our course with a study of brain anatomy and function, supplemented by hands-on learning in the classroom. We then began our study into an assigned protein of interest, where we will eventually learn to stain and visualize our protein in the lab at Karolinska. Our class was introduced to the multitude of public resources online generated by the Allen Institute for Brain Science, such as information on where it’s expressed in the brain and protein expression patterns in cell types. This coming week, we will present a coherent whole to the information we’ve found and discuss possible biological insights about our protein with our class, which I’m really excited about.

But before that…it was off to the airport to begin our weeklong Study Tour!

Days 1, 2, & 3: Vienna

To go on Study Tour in Vienna, in my opinion, was one of the most perfect choices to integrate place-based learning for this course. Vienna is not only home to some of the leading scientific institutions in the world for neuroscience research — it is often referred to as the “capital of classical music.” There’s a bit of an ongoing debate on whether Mozart sonatas can actually increase brain function or alleviate symptoms in patients with epilepsy, but music has long been used as a therapeutic tool in hospitals to aid recovery. In many ways, too, the brain works like music — just as the most complex symphonies arise from individual notes coming together in harmony, our functions and our thoughts are all the sum of individual neurons firing through synapses. As a longtime musician, I was excited to see the crossroads of two of my passions interact in Vienna.

Hundreds of years later, Vienna still pays homage to one of its most famous musicians: Wolfgang Amadeus Mozart, classical virtuoso. All of the members of the orchestra in the performance we watched at the Vienna Opera House were even dressed up as him!

On our first academic visit, we were welcomed by Dr. Sarah Melzer, whose group conducts research in how neuropeptides affect behavior and neuronal circuits at the Medical University of Vienna. We also met Dr. Lukasz Piszczek, a postdoctoral associate working with Dr. Wulf Haubensak who investigates neuronal circuits involved with emotional behavior. On a tour of their labs, we were introduced to patch-clamp electrophysiology, which measures changes in currents of cells in order to investigate the biophysical properties of ion channels.

Our first academic visit took us to the Center for Brain Research at the Medical University of Vienna, which is the hub of many neuroscience disciplines and discoveries at the institute.

We also saw multiple methods that the researchers were using to test mouse behavior, such as the open-field test and fear conditioning chamber. This was particularly interesting to me because I also work in a lab investigating the effects of early life stress on outcomes of autism and Tourette’s syndrome in mice. Before coming to Stockholm, I had spent the majority of the summer conducting behavioral tests, and it was fascinating to observe how different disciplines within neuroscience use modified but similar behavioral paradigms to investigate neuronal circuits of interest.

Our final academic stop in Vienna was the lab of a:head bio, where we listened to a lecture from Josh Bagley, the CSO of the company and a longtime neuroanatomist. The majority of therapeutic drugs for the central nervous system (brain and spinal cord) fail in clinical trials with humans–subsequently, those that succeed are overwhelmingly expensive. At a:head bio, the company’s unique approach to investigating novel therapeutics for neuropsychiatric disorders is to reprogram patient blood cells back to stem cells, then induce these cells to become miniature versions of organs called organoids (in this case, cerebral organoids, which are pictured below). This way, the researchers at a:head bio are able to monitor and measure disrupted electrical activity on organoid arrays to formulate new drugs, all outside of the body. I’d learned about iPSCs (induced pluripotent stem cells) before, but never outside a textbook — and it was such a cool experience to learn about the intricate process in which they are cultured, as well as some of the challenges that a:head bio has overcome in their hopes for pioneering this innovative technology. And to see the miniature brains and think that they were grown from something completely different in the body was truly amazing!

At Vienna, we also had the opportunity to experience and enjoy its unique culture in terms of travel, taste, and tone. Our walking tour and explorations took us around the Ring Road, where we marveled at the grandeur of the Hofburg Palace (the residence of the former Habsburg Dynasty), the serenity of the Belvedere Gardens, and the majestic, towering spires of the St. Stephen’s Cathedral. In those two days, we dined on staples of Viennese food: Griessnockerl, which were doughy dumplings in hearty beef soup; schnitzel, a delicious breaded pork cutlet with a generous helping of cranberry sauce; and the traditional apfelstrudel with creamy vanilla sauce. To wrap up Vienna, we attended a performance by the Vienna Mozart Orchestra at the State Opera House, where we heard stunning arias from Figaro and The Magic Flute and classics such as Turkish March, which the crowd joined in for, making for a lively and unforgettable night.

On our way home from the concert, a few of us accidentally stumbled upon Filmfestival Rathausplatz, a bustling bazaar with a row of international food stalls as far as the eye could see, the scene accompanied by vibrant music from An American in Paris, all under the facade of the majestic city hall. The spectacular exposition was the perfect ending to our trip in Vienna. I came away from this leg of the trip feeling an overwhelming flurry of emotions: wonder at all of the novel ideas and experiences, a curiosity to see and learn more, and gratefulness to be making new close connections with my fellow peers.

Development (n.): 1) transformation of initial musical themes and ideas presented; the second section of a classical sonata 2) the series of changes that occur during the life history of an organism

Days 4 and 5: Budapest

I’ll never forget our first full day in Budapest. It started with a morning visit to the Semmelweis University in Budapest, where we discussed the significance of neurulation (a critical step in the proper development in the brain) with Dr. Alán Alpár, professor of Embryology, Histology, and Anatomy. The discussion was supplemented with a demonstration — a dissection of a human brain donated to the university. Even though I’ve seen jars of preserved brains and some neurosurgeries before, there was something very special about seeing the sharp knife slice a brain cleanly in half, exposing a perspective of the brain usually only seen in textbooks — a sight I’ve never seen in real life in a traditional classroom. “You may touch it,” he invited us.

Our first academic stop in Budapest was at the Semmelweis University, one of the leading medical institutions in the world.

A quieting wonder settled over the sterile room as we cradled this organ in our hands–this weighted, spongy mass the size of a grapefruit, yet so incredibly important. It was a privilege to be able to interact with such a well-preserved human brain, to handle the delicate treasure responsible for everything we know. We also got the opportunity to see a dissected cadaver that had taken six months to assemble, which was a truly surreal sight. It was this visit that allowed me to realize how far we had come in understanding the brain — but also the vastness of the unknown frontier of neuroscience.

We were given the rest of the day to explore Budapest on our own, and we grabbed lunch at the Great Market Hall, a marketplace lined with a plethora of shops selling everything from lavender to chimney cakes to téliszalámi (smoked sausage). Initially, I wasn’t sure if anything could top the beauty of Vienna’s polished Baroque buildings. But when we climbed to the summit of the Liberty Statue overlooking the Danube River (which separates Buda and Pest) I was speechless — the view of the city over the clear blue waters was absolutely breathtaking. My sense of wonder didn’t fade all day as we made our way to the majestic Buda Castle and walked across the ramparts of the ancient Fisherman’s Bastion, a Romanesque work of art in its own right.

The night concluded with a walking food tour of the city, where we visited historical memorials of Budapest and sampled traditional Hungarian cuisine, the first time I’ve ever tried it. We tasted freshly-baked strudels that ranged in flavors from poppyseed to cabbage; langos, fried bread topped with sour cream and cheese; goulash, a hearty, thick soup spiced with paprika and filled with beef and potatoes, and lastly, a sampling of túrógombóc, a cottage cheese dessert. Everything was so delicious!

Last but not least, we ended our trip to Budapest on an academic visit to the KOKI Institute of Experimental Medicine with Dr. Ádám Dénes, where we learned about the importance of microglia (a type of supporting cell in the brain), which aids in pruning synapses to make space for normal brain development. Dr. Dénes emphasized that if we are able to detect impairment or changes in normal functions of microglia before onset of symptoms, it could be a major step in active prevention of neurodegenerative disorders — an ambition I hope to closely follow the progress of in the future.

Recapitulation (n.): bringing the themes and main ideas all together again at the end; the third section of a classical sonata

I absolutely loved the Study Tour — it was unlike anything I’d ever experienced before, and I returned to Stockholm with a fresh new perspective on many aspects of neuroscience, culture, and connections. Unlike the majority of DIS classes this summer, our class went on Study Tour the second week of the session — which, in my opinion, was the most fitting in terms of academic schedule and class interaction. The opportunity to visit so many different academic institutions and labs in Budapest and Vienna truly opened my eyes to new ways at looking at the brain, with some of the most memorable place-based learning I’ve ever encountered. The Study Tour not only introduced us to a plethora of fascinating research and neuroscience concepts in the field, it really gave us a chance to meet one another, and I am grateful for all of the connections and memories that I’ve made with my fellow peers.

It is surreal to think that three weeks ago, I had never stepped foot in Europe before, met any of my current classmates, or heard of the Allen Brain Atlas. Today, I’ve just returned from an intense laser tag session in Stockholm Laserdome with my class to celebrate two birthdays. Today, I am getting ready to present a publication figure I’ve created with information on my protein from five different brain atlases, integrating information I learned in class and the place-based learning opportunities I’ve had. Today, nostalgia for the culture and cuisine of Budapest-Vienna hits me when I inhale the fragrant scent of a lavender sachet and hear the haunting notes of Mozart’s D minor sonata on my headphones — and I promise that I will return.

After returning from Study Tour, I’ve found a community of friends in my class, and cannot wait to experience the rest of our time in Stockholm together with them.

Song Recommendations:

Vienna by Billy Joel, on the plane from Stockholm to Vienna

Queen of the Night aria from The Magic Flute by Wolfgang Amadeus Mozart, during late night rain

La Campanella by Franz Liszt, on a stroll through Buda Palace

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