Blanchette and Scalera et al., discover new insights into an intercellular communication method in neurons

Fruit fly neuron (magenta) with extracellular vesicle cargoes (green). Cargoes are packaged inside the neuron and, then released outside of the neuron in extracellular vesicles.

Research scientist Cassie Blanchette and Neuroscience Ph.D. student Amy Scalera, working in the Rodal lab, discovered a new mechanism of regulation of extracellular vesicles (EVs). EVs are small, membrane-bound compartments that can transfer cargoes such as DNA and proteins between cells for communication. EVs are important for normal cell-cell signaling, but they are also hijacked in neurodegenerative disease to spread toxic disease proteins to other cells. Therefore, it is crucial to understand how and where EVs are formed. Blanchette and Scalera discovered a novel method of regulation of EVs specifically at the synapses (the region of the neuron that contacts adjacent cells), using the fruit fly nervous system as an experimental model.

EVs are derived from endosomes, a network of intracellular sorting compartments that cells use to separate cargoes into different ‘packages’ with distinct inter and intracellular destinations. Blanchette and Scalera found a surprising function for the proteins that regulate endocytosis, a process in which the cell membrane buds inward, thus forming a compartment to bring cargoes to endosomes. The authors found that mutants lacking endocytic proteins lose the local pool of EV cargoes that are available for release from synapses, and instead send these cargoes for disposal elsewhere in the neuron. They hypothesized that the normal function of endocytosis  is akin to a plane circling in a holding pattern at an airport – while it waits for its time to land, it is better for the passengers to circle (between the cell membrane and endosomes), nearby their destination (release in EVs), rather than being sent to an entirely different city (a different region of the neuron). They also found that disrupting this holding pattern had consequences for the physiological functions of EV cargoes; in endocytic mutants, loss of Synaptotagmin-4, an EV cargo important for neuronal adaptability, was associated with failure of the neuron to grow in response to firing. Endocytic mutants also caused synaptic depletion of the Alzheimer’s disease associated EV cargo Amyloid Precursor Protein (APP), thus suppressing its toxicity and increasing the survival of APP-expressing flies. These discoveries raise the possibility that proteins regulating EV traffic may be targets for neurodegenerative disease therapies.

Divisional Prize Instructors design & teach new classes

The University Prize Instructorships have been a great opportunity for our graduate students to gain experience designing and teaching their own class, and a great opportunity for our undergraduates to engage in learning new areas with a great instructor. When the UPIs were put on hiatus during the pandemic, the Division of Science stepped in to keep this opportunity going for our community. We are really excited for the new courses that will be taught by Xin Yao Lin and Narges Iraji in the Spring 2022 semester- “Science versus Science Fiction” by Narges Iraji, and “Technology Use and Well-Being: Multidisciplinary Perspectives”.

Xin Yao Lin

Xin Yao LinI am very honored and delighted to receive the Divisional Prize Instructorship. I am currently a 5th-year psychology PhD student and I will be teaching a psychology course entitled “PSYC 55B: Technology Use and Well-Being: Multidisciplinary Perspectives” in the spring of 2022. The increase in technology use is changing how we connect, feel, and act. We are relying on technology more than ever, but whether the increased usage of technology is beneficial or detrimental to well-being has been controversial. Drawing on perspectives from psychology, neuroscience, computer-human interaction, and public health, this course explores the positive and negative impact of technology usage on our well-being across the lifespan. We will examine technology use in computer-mediated communication (e.g., smartphone, social media, internet, social apps), mHealth and telehealth, gaming, and other technology trends (e.g., Artificial intelligence, robots, virtual reality), and will explore how these technologies influence social life, adult development and aging, and health/health behavior (e.g., physical activity, diet, sleep).

I am very thankful for this opportunity provided by the Division of Science, and for my mentors and peers who have provided feedback and supported me along the way. I look forward to teaching this course and engaging students with how technology influences our social life, how we develop and age, and our health/health behavior.

Narges Iraji

Narges IrajiThe course Science and Science Fiction, designed for students with little to no science or math background, encourages conversations around science within the context of culture. Reading the works of science fiction by a diverse group of authors and discussing the science and imagination in them illuminates the inseparability of science from its human nature. I hope that this approach not only bridges the materials taught in class and the outside world but also sparks a curiosity that goes beyond the classroom.

Our inner urge to observe, decode patterns, and predict has existed well past the modern times and so has our passing of knowledge to the future in the form of storytelling. The combination of imagination and science is nothing new but the access to both, who can imagine and who can be a scientist, has changed throughout history. During the course, the students will read, discuss, and write about science fiction stories that inspire questions and problems which call for mathematical modeling. After becoming more familiar with some well-known mathematical models in areas such as population modeling and epidemiology, the students start working on a final project. They will formulate a question related to what they are passionate or curious about and pursue the answer using the tools that they have gained from the course. The goal is not to solve the problem, but to gain some insight into the steps required in doing so.

Teaching a University Prize Instructorship course has been a dream of mine since I heard about this opportunity in my first or second year. I am grateful for this, and thankful to all those who are helping me along the way. Numerous challenges follow developing a course, and while being one of the greatest projects that I have taken on, it has tested my patience a few times. I hope that after serving as a University Prize Instructorship instructor, I can help other graduate students who are interested in this opportunity by sharing some resources, such as information on inviting speakers or reserving classrooms with computers. My experience as a graduate student in physics and my research in the field of mathematical biology have truly led me to a new perspective. I now look around and find questions in all that I observe knowing someone else might have already started working on the answer. The course, Science and Science Fiction, encapsulates one of my attempts to pass this curiosity about the universe and life forward.

New Undergraduate Engineering Science Program Approved

Technology is central to our society. Universities play a key role as innovation hubs in new technology development, by linking knowledge creation, workforce development and commerce. After a multi-year planning process with Brandeis stakeholders and Engineering education experts, the Brandeis Faculty and Board of Trustees has approved the creation of a distinctively Brandeisian undergraduate Engineering Science program, designed for ABET accreditation. Unlike other models in which Engineers are siloed in their own department or school, this interdepartmental program is designed to  maximize horizontal integration across and beyond the Sciences.  All hands are now on deck to make this program a reality.  Institutional Advancement is working closely with faculty to raise the funds necessary to meet our ambitious goals.

Science Engineering LogoTo build up this program, we will  capitalize on the existing synergy between the life and physical sciences, while enhancing core research areas with an emphasis on translating basic research to technological applications.  Our goal is to integrate the engineering curriculum with the social justice mission that is integral to Brandeis. We envision providing opportunities for our students and faculty to deeply engage in science, design, and problem-solving while participating in a curriculum and culture that grapples with issues of social justice, business ethics and sustainability. The curriculum will be designed with these aspirations by engaging faculty from all of arts and sciences, IBS and Heller.  Ultimately, we hope that this new program will give our students the tools to intervene in the world and challenge them to build a better one.

We welcome input from our friends and alums as we begin to engage in the task of building up this exciting new program.

Grants for undergraduate research in computational neuroscience

The Division of Science is pleased once again to announce the availability of Traineeships for Undergraduates in Computational Neuroscience through a grant from the National Institute on Drug Abuse. Traineeships will commence in summer 2021 and run through the academic year 2021-22.

From former trainee Dahlia Kushinksy’s first-author paper published in Journal of Experimental Biology, “In vivo effects of temperature on the heart and pyloric rhythms in the crab, Cancer borealis”

Please apply to the program by March 2, 2021 at 6 pm to be considered.

 

Traineeships in Computational Neuroscience are intended to provide intensive undergraduate training in computational neuroscience for students interested in eventually pursuing graduate research. The traineeships will provide approximately $5000 in stipend to support research in the summer, and $3000 each for fall and spring semesters during the academic year. Current Brandeis sophomores and juniors (classes of ’22, ’23) may apply. To be eligible to compete for this program, you must

  • have a GPA > 3.0 in Div. of Science courses
  • have a commitment from a professor to advise you on a research project related to computational neuroscience
  • have a course work plan to complete requirements for a major in the Division of Science
  • complete some additional requirements
  • intend to apply to grad school in a related field.

Interested students should apply online (Brandeis login required). Questions may be addressed to Steven Karel <divsci at brandeis.edu> or to Prof. Paul Miller.

Turrigiano lab uncovers sources of neuronal heterogeneity

High activity neurons have greater instrinsic excitability and response to local inputs, but no difference in total input type or amount

Mammalian cortex has long been one of the most widely studied systems in neuroscience, dating back to the pioneering work of Santiago Ramon y Cajal in the late 19th century. The cortex is much larger in primates than other mammals, and is thought to be responsible for the advanced cognitive abilities of humans. Today, models of cortical connections and computations form the basis for some of the most powerful deep learning paradigms. However, despite this success, there is still much that is unknown about how cortex functions. One feature of cortex that has recently been discovered is that neurons that appear to be similar to each other can have very different baseline activity levels: some neurons are 100x more active than their neighbors. We don’t know how neurons that are otherwise highly similar in shape and genetic makeup can maintain such different activity levels, or if the neurons with high and low activity levels have different functions in the brain. These neurons are otherwise so similar to each other that it is difficult to tell them apart without recording their activity directly, and current techniques for recording the activity of many neurons simultaneously in live animals do not allow us to later re-identify them for further study.

In a paper recently published in Neuron, the Turrigiano lab, led by postdoctoral researcher Nick Trojanowski, reported a new approach for permanently labeling high and low activity neurons in live animals, and then determining what makes them different. To do this they used a fluorescent protein called CaMPARI2 that changes from green to red as activity increases, but only when exposed to UV light. By shining UV light into the brain, they caused neurons with high activity to turn red, while neurons with low activity remained green. This procedure allowed them to run a series of tests on high and low activity neurons to identify differences between them. They found that high activity neurons would intrinsically generate more activity than low activity neurons when presented with the same stimulus. These high activity neurons also receive more excitatory input specifically from nearby neurons of the same type. Surprisingly, however, they found that the total amount of excitatory and inhibitory input that high and low activity neurons received from other neurons was not a major factor in determining their activity levels. Together, these results tell us that the differences in activity between neurons are due to intrinsic differences, as well as their pattern of connectivity to their nearby partners. This has deep implications for how the networks that underlie cortical computations are built and maintained.

With these tools in hand, it is now possible to further explore the differences between high and low activity neurons. Do these neurons serve different functions? Are the baseline activity levels specified from birth? How do these activity levels affect the mechanisms of plasticity that are responsible for learning and memory? The recently published results represent just the tip of the iceberg of information that can be learned with this new technique, in the mammalian cortex as well as other brain regions.

Griffith lab finds that time-keeping brain protein influences memory

Figure from Griffith lab paperIn the Journal of Neuroscience, members of the Griffith Lab found that memory impairments can result from disruptions in the release of the peptide Pigment-dispersing factor (PDF). PDF aligns the brain’s time-keeping mechanism to the correct time of day.

Upsetting the brain’s timekeeping can cause cognitive impairments, like when jetlag makes you feel foggy and forgetful. These impairments may stem from disrupting a protein that aligns the brain’s time-keeping mechanism to the correct time of day, according to new research in fruit flies published in JNeurosci.

The brain contains ‘clock’ neurons that collectively mold circadian behaviors and link them to cues from the environment, like light and seasonal changes. In fruit flies, the peptide Pigment-dispersing factor (PDF) is released from the clock to both synchronize the activity of the clock neurons and to drive time-based behaviors like mating and sleep. PDF may also underlie memory formation, explaining the cognitive dysfunction that occurs when the clock is desynchronized from the environment.

Flyer-Adams et al. tested how well fruit flies with a functioning core clock, but lacking the PDF output signal, could learn. They found that without PDF signaling, flies had severely impaired memory. Interestingly, memory regulation by PDF likely occurs without direct signaling to the main memory structure of flies. Their results suggest that PDF from the clock may promote normal memory throughout the day by acting as a timestamp to learning. The VIP pathway in humans may play a similar role.

Publication:

Regulation of olfactory associative memory by the circadian clock output signal Pigment-dispersing factor (PDF). Johanna G. Flyer-AdamsEmmanuel J. Rivera-RodriguezJunwei YuJacob D. MardovinMartha L. Reed and Leslie C. Griffith. 

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