New Computational Neuroscience Textbook

Paul Miller bookComputational Neuroscience is an exciting branch of science, which is helping us understand how simple biophysical processes within cells such as neurons lead to complex and sometimes surprising neural responses, and how these neurons, when connected in circuits can give rise to the wide range of activity patterns underlying human thinking and behavior. To bridge the scales from molecules to mental activity, computer simulations of mathematical models are essential, as it is all too easy for us otherwise to produce descriptions of these complex interacting systems that are internally inconsistent. Simulations allow us to ask “given these ingredients, what is possible?”

Simulation showing how weaker input that is localized can produce spiking when stronger dispersed input does not.

The best way to study computational neuroscience is to write the computer codes that model a particular biological phenomenon, then see what the simulation does when you vary a parameter in the model. Therefore, the course I teach at Brandeis (NBIO 136B) is based around a large number of computer tutorials, in which students, some of whom have no computer-coding background, begin with codes of 5-10 lines that simulate charging of a capacitor, and end up completing codes that simulate the neural underpinnings of learning, pattern recognition, memory, and decision-making. It turns out that very few computational principles are needed to build such codes, making these simulation methods far more easily understood and completed than any mathematical analysis of the systems. However, in the absence of a suitable introductory textbook—most computational neuroscience textbooks are designed by Ph.D. physicists and mathematicians for Ph.D. physicists and mathematicians—it proved difficult for me to use the flipped classroom approach (see below). Therefore, my goal was to create a text that students could read and understand on their own.

Different behaviors of a three-unit circuit as connection-strengths are changed. (Multistable constant activity states, multiple oscillating states, chaotic activity, heteroclinic state sequence). Each color represents firing rate of a unit as a function of time.

In keeping with the goal of the course—to help students gain coding expertise and understand biological systems through manipulations of computer codes—I produced over 100 computer codes (in Matlab) for the book, the vast majority of which are freely available online. (All codes used to produce figures and some tutorial solutions are accessible, but I retained over half of the tutorial solutions in case instructors wish to assign tutorials without students being able to seek a solution elsewhere.)

Learn more at MIT Press.

From the Preface of the book:

I designed this book to help beginning students access the exciting and blossoming field of computational neuroscience and lead them to the point where they can understand, simulate, and analyze the quite complex behaviors of individual neurons and brain circuits. I was motivated to write the book when progressing to the “flipped” or “inverted” classroom approach to teaching, in which much of the time in the classroom is spent assisting students with the computer tutorials while the majority of information-delivery is via students reading the material outside of class. To facilitate this process, I assume less mathematical background of the reader than is required for many similar texts (I confine calculus-based proofs to appendices) and intersperse the text with computer tutorials that can be used in (or outside of) class. Many of the topics are discussed in more depth in the book “Theoretical Neuroscience” by Peter Dayan and Larry Abbott, the book I used to learn theoretical neuroscience and which I recommend for students with a strong mathematical background.

The majority of figures, as well as the tutorials, have associated computer codes available online, at github.com/primon23/Intro-Comp-Neuro, and at my website. I hope these codes may be a useful resource for anyone teaching or wishing to further their understanding of neural systems.

 

SciFest VIII will be on Thursday, Aug 2

Scifest VIII, our annual Poster Session featuring undergraduate researchers, will be held on Thursday, August 2. The poster session will be 1:00 to 3:00 pm in the Shapiro Science Center atrium.

SciFest features undergrads who have spent their summers working in both on-campus and off-campus labs doing scientific research, usually alongside grad students, postdocs and faculty members. It an opportunity for these dedicated students from across the Division of Science, including summer visitors and Brandeis students, to present their research for peers and the community.

As of today, 107 students have registered to present.

The public is invited to attend and to discuss research with the students. As always, refreshments will be served.

“Lessons from the Lobster” details Eve Marder’s research

Lessons from Lobster. Photo courtesy of MIT.By Eve Marder

Students often tell me that they don’t want to be scientists because it is too lonely. That always surprises me, because laboratories are filled with people. One of the conclusions that readers of Charlotte Nassim’s “Lessons from the Lobster” should take from the book is that laboratories are communities of scholars of all ages. Lifelong friendships are often formed and sustained as laboratory colleagues may spend as much time together as they do with other friends and family. When Charlotte approached me about writing the story of my research, I was very surprised because there are many eminent neuroscientists, including many other eminent female neuroscientists. What convinced me to work with Charlotte was her wish to reach teenage girls, before they decided that a career in science was not for them. And this decision was validated when a few days ago, one of the students (now working in a neighboring lab) whom I had taught in NBio 140, Principles of Neuroscience, told me that she loved the book, but wished she had had it when she was in high school. We agreed that after she finished the book, that she would donate it to her small home town library, in the hopes that it would encourage other high school students to consider becoming scientists.

Charlotte’s book is a piece of science history. She read our lab notebooks, and talked to many ex-lab members. Her choices of what to emphasize and how to frame the scientific issues speak as much about what she finds scientifically and sociologically interesting as it does about what I was thinking. By reading deeply, she relied not only on my flawed memory, but on what I and others had written. For me, it is an extraordinary reminder that even scientists who revere data have only partial recollections of their own intellectual paths.

Paradis and Van Hooser labs collaborate on eLife paper

Figure 3 from research paper

Figure 3. Rem2 is required for late-phase critical period ocular dominance plasticity.

“Rem2 stabilizes intrinsic excitability and spontaneous firing in visual circuits.” Anna R Moore, Sarah E Richards, Katelyn Kenny, Leandro Royer, Urann Chan, Kelly Flavahan, Stephen D Van Hooser, Suzanne Paradis. eLife 2018;7:e33092.

Throughout our waking hours, we experience an ever-changing stream of input from our senses. The brain responds to this varying input by adjusting its own activity levels and even its own structure. It does this by changing the strength of the connections between neurons, or the properties of the neurons themselves. Known as plasticity, this process of continuous change enables the brain to develop, learn and to recover from injury.

The visual systems of mammals are particularly well suited to studying how sensory experience alters the brain. Studies in animals show that lack of sensory input to one or both eyes during a critical period in development causes long-lasting changes in the brain’s visual circuits. Similarly, children with the condition amblyopia or ‘lazy eye’ – in which one eye has impaired vision and the brain ignores input from that eye – can end up with permanent deficits in their vision if the condition is not treated during childhood. Changes in sensory input are thought to trigger plasticity in the brain by altering the activity of specific genes. But exactly how this process works is unclear.

Anna Moore, Sarah Richards et al. now show that a gene called Rem2 has an important role in regulating visual plasticity. In the key experiments, young mice had their vision in one eye blocked for a few days. Analysis of their brains showed that mice that had been genetically modified to lack the Rem2 gene responded differently to this change in their environment (i.e. the loss of input to one eye) than their normal counterparts. Further experiments suggest that Rem2 regulates the excitability of individual neurons: that is, how much the neurons respond to any given input. In the absence of Rem2, neurons in visual areas of the brain become hyperactive. This prevents them from adjusting their activity levels in response to changes in sensory input, which in turn leads to impaired plasticity.

Being able to harness the brain’s visual plasticity mechanisms on demand, for example by regulating Rem2 activity, could benefit individuals with disorders such as amblyopia. Rem2 is also active in many other parts of the brain besides those that support vision. This suggests that manipulating this gene could affect numerous forms of plasticity. However, various barriers must be overcome before we could use this approach to treat brain disorders. These include obtaining a more in depth understanding of the role of the Rem2 gene in the human brain.

Raul Ramos Pays It Forward in His Home State of Texas


photo credit: Simon Goodacre

Helen Wong | Graduate School of Arts and Sciences

Raul Ramos, a fourth-year Ph.D. candidate in Neuroscience, spent the five-hour flight from Boston to Austin, Texas trying to think of what to say to a classroom full of adolescents who had been sentenced to juvenile detention, like he had been once when he was a teenager.

“I was trying to get into the mindset of it all,” he says of those nerve-wracking hours before arriving in Austin. “I was trying to remember how I felt when I had been in their shoes.” He had put together a talk and a script, but the moment he entered the first classroom at the Austin Alternative Learning Center, all of it went out the window. “Instead of giving a lecture, I had an actual conversation with the kids,” says Ramos. “They could relate to me. I was someone who looked like them, talked like them, moved like them. So they listened when I told them about my story and how, despite what they were facing now, their outcomes could be different too.”

Ramos first started working with high school students after he moved to Waltham. Anique Olivier-Mason PhD’12, Director of Education, Outreach and Diversity at the Materials Research Science and Engineering Center had arranged “Pizza Talks,” a program where graduate students in the sciences visit classrooms at Waltham High School and discuss their decisions to pursue careers in science, their experiences as investigators and their research. The program has been a great success and now serves as the model for similar talks taking place nationally, sponsored by the American Association for the Advancement of Science (AAAS). Ramos volunteered to give a talk when he first heard about the program.

“Waltham High has a large Hispanic student population,” says Ramos. “These groups underrepresented in science. I really liked going to speak to them and talking about my own journey and its relation to my identity.” AAAS became aware of this community outreach and contacted the university to learn more. Ramos has always been open about the troubles in his own past, so when AAAS were looking for scientists to speak to students in alternative learning centers in Austin, they asked him if he would like to go. “I said yes, of course,” says Ramos. “I’m from Texas originally, so I agreed to fly down and talk to the kids.”

What began as originally just one or two schools became six upon his arrival in Austin as word got around of his visit. During the trip, Ramos gave sixteen talks and spoke to around two hundred students. “I went to juvie centers, alternative learning centers, drug rehabilitation facilities,” he says. “The level of engagement was amazing. For every kid that didn’t want to engage, there were a few more who wanted to talk to me and learn about how I’d gotten to where I am. One of the most frequent questions they asked me was, ‘Sir, what do I do when I get out of here?’ and I would tell them the truth. I told them that once they got out, they would have to actively avoid situations and people that would get them in trouble. I said that if that meant having to hole up in their room to study and get away from it all, then doing that would absolutely be worth it in the long run. Their environment matters.”

But even after telling them his advice, Ramos knew that advice alone wasn’t going to be enough for many of the kids he was speaking to. “You need a support network,” he says. “A lot of these kids don’t have that. Some of them are safer in detention than at home. So many of them are angry–why wouldn’t they be? They’re supposed to become upstanding members of society, but the way the system goes about that is to lock them up and isolate them. That’s not how rehabilitation should work.”

At some of the facilities he visited, Ramos saw kids as young as eleven or twelve being escorted by armed guards from classroom to classroom despite some of them being barely half his size. For Ramos, the sight was jarring. “It looks like overkill,” says Ramos. “I know they’re here because they did something wrong, but at the end of the day, they’re just kids.”

It also struck Ramos, as he made the rounds in each facility, that the kids incarcerated at these centers were all people of color despite Austin being in a majority white part of Texas. “Brandeis is all about recruiting underrepresented minorities into its science programs,” he says. However, the challenges of recruiting students of color for doctoral programs in science are significant, and Ramos realized during his trip to Texas that “part of the reason for the absence of black and brown individuals in science was that so many of them, who could potentially be scientists someday, are stuck in juvie–stuck in environments that deprive them of opportunities and healthy role models.

“And people like me that manage to get an education, we make it out and we leave. We come over here to go to college, we leave Laredo [Ramos’ hometown], and these kids don’t get to have good role models. They make mistakes fueled by a terrible home environment and get stuck in the juvie-to-prison pipeline. They repent and feel bad in juvie, but once they get out, if they don’t have a support network, it starts all over again. The system tries them as full adults at seventeen, when they’re not even old enough to vote. Things have to change. I want to help make that happen and to show them that right now, there are still opportunities open to them.”

Despite all of the system’s shortcomings, the alternative learning centers and similar institutions are making a tangible difference. “The system’s not perfect,” says Ramos. “It’s deeply flawed. But things are already better now than when I was in. Back then, I was put in what would conventionally be considered a prison cell. At least most of these kids get an education, space to walk, and are surrounded by people who care about them. Everyone working at the Austin Alternative Learning Center was so motivated and clearly cared about the kids.”

Upon his return to Brandeis, Ramos decided that he would dedicate more time to community outreach and consider the possibility of working in science policy after earning his doctorate. He wants to do work that not only has value in the scientific world, but that also actively helps bolster diversity and inclusion in the field, helping fight back against larger societal and institutional structures that disadvantage people of color.

“We need representation to show kids that the journey is possible,” says Ramos. “The cards feel like they’re stacked almost the entire way through. I’m going to do whatever I have to do to get the message out there to those kids who are hardest to reach and who need to hear from us the most.”

Brandeisians Receive 2018 NSF Graduate Research Fellowships

NSF Graduate Research FellowshipFive Brandeisians (past and present) have received NSF Graduate Research Fellowships for 2018. Also, one current graduate student received an honorable mention.

This program recognizes and supports outstanding graduate students in NSF-supported STEM disciplines who are pursuing research-based advanced degrees at U.S. institutions. In 2018, the National Science Foundation (NSF) received over 12,000 applications, and made 2,000 award offers. This fellowship provides three years of financial support within a five-year fellowship period ($34,000 annual stipend and $12,000 cost-of-education allowance to the graduate institution).

Alyssa Garcia, a Brandeis Physics graduate student, received a fellowship. Marcelle Soares-Santos, Assistant Professor of Physics, is Alyssa’s advisor. Marcelle said “Alyssa will work on obtaining a sample of neutron star collisions with the goal of using them as standard sirens to determine the rate of expansion of the Universe.  This is very timely after the discovery of the groundbreaking neutron star collision GW170817 as the gravitational wave detectors are now being upgraded and when they come back later this year, they are expected to yield almost 10 times more detection’s per year. That wealth of data, is a very exciting prospect for a student starting their PhD career!”

Christopher Konow, a Ph.D. candidate in Chemistry, received an honorable mention. He works in the Irving Epstein lab analyzing the Turing Pattern formation in Growing Domains using the CDIMA (chlorine dioxide-iodine-malonic acid) chemical reaction.  For the NSF GRF, he proposed developing a novel self-oscillating hydrogel that could have uses in drug delivery.  He plans to start this project in late summer/early fall of 2018.

The Brandeis undergraduate alumni receiving 2018 NSF GR fellowships are:

  • Caroline Cappello graduated in 2011 with a bachelor’s degree in Environmental Studies and Theater Arts. She is a Ph.D. student in the Department of Biology at the University of Washington.
  • Emma Chad-Friedman received a BA in Psychology and Anthropology in 2014 and is in the PhD. Psychology program at the University of Maryland at College Park.
  • Jung Park also graduated in 2014 with a degree in Neuroscience and Psychology. He is currently a Ph.D. student in Neurobiology and Behavior at Columbia University.
  • Stanislav Popov received his B.S. degree in Mathematics and Chemistry only 2 years ago (2016). While at Brandeis, Stanislav worked in Isaac Krauss’ lab. He is pursuing a Ph.D. in Chemistry at UCLA.

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