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.

Learning from how viruses assemble

Capsid image from paper

credit: eLife

Michael Hagan, Professor of Physics, is quoted extensively in the Chemical & Engineering News article, Lessons learned from watching viruses assemble. The paper discusses how scientists are studying the ability for viruses to self-assemble. During a viral infection, infected cells manufacture the genetic material and other components of the virus. These components then self-assemble, or build themselves into complex shapes, to form new viruses capable of infecting additional cells.

Many viruses contain their genetic material within a protective shell known as a capsid. Michael Hagan is one of the scientists studying how these capsids are formed by modeling the conditions and chemical properties that allow viruses to build themselves. Once understood, researchers hope this will help in drug design and delivery.

Article: Lessons learned from watching viruses assemble, Laura Howes, Chemical & Engineering News-C&EN,  December 15, 2020.

First Rosbash-Abovich Award Recipients Announced

Michael Rosbash, the Peter Gruber Endowed Chair in Neuroscience and Professor of Biology and his wife, Nadja Abovich, established the Rosbash-Abovich Award as a way to inspire and acknowledge excellence in research by post-doctoral fellows and graduate students in the Brandeis life sciences. The Rosbash-Abovich award will be awarded annually.

The award honors the most outstanding papers published the previous year that have been authored by a Brandeis postdoctoral fellow and a Brandeis PhD student. In addition to the honor being selected, each winner is presented with a monetary award.

Future winners will present their talks at upcoming Volen Scientific Retreats, but due to COVID restrictions, the 2020 winners will be presenting their talks during the Molecular Genetics Journal Club meetings.

Most outstanding paper by a post-doctoral fellow

Michael O'Donnell

Michael O’Donnell, PhD

The 2020 winner for the most outstanding post-doctoral paper is Michael O’Donnell for the publication titled “A neurotransmitter produced by gut bacteria modulates host sensory behavior“. O’Donnell, is a former postdoc in the Piali Sengupta Lab. Sengupta said

Mike is a remarkable scientist and mentor. He single-handedly and independently established a new research direction in my lab. He also served as an informal mentor to many graduate students and has continued to do so even after he left my lab. I greatly appreciated our long discussions and arguments, and he is very much missed.

Sengupta also noted that O’Donnell was chosen to receive this award

on the basis of the creativity and novelty of his work that was published in Nature. The committee was particularly interested in nominating a researcher who was a driving force behind the work and Mike certainly fulfilled this criteria.

O’Donnell is now an assistant professor at Yale and recently formed the O’Donnell lab. He presented his talk to the Molecular Genetics Journal Club on December 2, 2020. He spoke about his work on neuromodulators produced by different bacteria.

Most outstanding paper by a PhD student

James Haber & Gonen Memisoglu

Professor James Haber & Gonen Memisoglu, PhD

The recipient of the 2020 award for the most outstanding PhD student paper is Gonen Memisoglu for the publication “Mec1 ATR Autophosphorylation and Ddc2 ATRIP Phosphorylation Regulates DNA Damage Checkpoint Signaling.“ She was a PhD student in James Haber’s lab. She received her PhD in 2018 and is currently a postdoctoral fellow at the University of Chicago. She will be presenting her talk at the Molecular Genetics Journal Club on February 2, 2021.

When asked about his former PhD student, Haber said

I was delighted to learn that Gonen was the recipient of the Rosbash/Abovich award for the best publication by a graduate student last year; but I had to ask “which paper” because Gonen made two important discoveries last year about the way cells respond to DNA damage. Gonen helped develop a highly efficient way to edit the yeast genome and to create dozens of very precise mutations in the Mec1 gene that is the master regulator of the DNA damage response.  When there is a chromosome break, the Mec1 protein phosphorylates a number of proteins that creates a cascade of signaling to prevent cells from progressing through mitosis until damage is repaired. Gonen discovered that the extinction of the this signal depended on Mec1’s autophosphorylation of one specific target and that changing that specific amino acid to one that could not be phosphorylated was enough to cause cells to remain arrested. She also identified several alterations of the Ddc2 protein that associates with Mec1 that were also critical for its normal activation.

During her time in my lab Gonen was a super hard-working and exceptionally insightful grad student, but also incredibly generous with her time, helping others in the lab

Bulbul Chakraborty Elected AAAS Fellow

Bulbul ChakrabortyBulbul Chakraborty, the Enid and Nate Ancell Professor of Physics and head of the Division of Science, has been named a Fellow by the American Association for the Advancement of Science. This honor is in recognition of Professor Chakraborty’s important theoretical contributions in the area of condensed matter physics, particularly disordered systems including frustrated magnets and granular materials.

Chakraborty has been a Brandeis faculty member since 1989. She is a condensed matter theorist who is currently focused on understanding the emergence of rigidity in solids that emerge in strongly nonequilibrium processes such as jamming or gelation.

A virtual induction ceremony for the newly elected Fellows will be held in February 2021.

Read more: BrandeisNow

Grace Han named Landsman Career Development Chair in the Sciences

Grace Han, Assistant Professor of Chemistry, has been appointed the Landsman Career Development Chair in the Sciences. Lisa Lynch, Provost and Dorothy Hodgson, Dean of Arts and Sciences, noted that Han’s work as a “scholar, a teacher, and an advisor, makes [her] highly deserving of the Landsman Chair.”

Grace directs the Han Group at Brandeis. This lab, whose scientific inquiry focuses on light-matter interaction in various material systems that range from photo-switching molecules to inorganic 2D crystals.  Her team seeks to develop optically-controlled molecular switches for energy conversation and storage and optoelectronic applications.

Grace’s research has resulted in a project, “Optically-Controlled Functional Heat Storage Materials,” which was featured in Chemical and Engineering News upon being granted Brandeis SPROUT Awards in 2019 and again in 2020.  In this work, the Han Group developed materials that recycle waste heat from a running engine and warm up frozen oil upon triggering to facilitate car startups in northern climes.  The Han Group is currently developing the initial prototype for the device containing the functional energy material.

At Brandeis, Grace teaches “Inorganic Chemistry,” “Polymer and Inorganic Materials Chemistry,” and “Chemistry Colloquium.”  She is co-chair of the Graduate Student Admissions Committee and of the Departmental Colloquium Committee and is also a member of the Graduate Studies Committee. Grace has most recently co-authored articles for the Journal of the American Chemical Society, Chemistry of Materials, and ACS Nano.

The Landsman Chair was established in 2015 through a gift from Dr. Emanuel Landsman. The Landsman Chair reflects his deep commitment to nurturing rising young scientists.

Longtime supporters of the University, Manny and his wife, Sheila Landsman, also gifted the funds used to build the Landsman Research Facility. This is the structure that houses an 800 MHz magnetic resonance spectrometer. The 15,000-pound superconducting magnet is used by scientists to search for solutions to neurodegenerative diseases and cancer.  Dr. Landsman co-founded the American Power Conversion Corporation, served on the Brandeis University Science Advisory Council for many years, and was named a Brandeis Fellow in 2008.  The Landsmans’ grandson, Wiley Krishnaswamy, is a member of the Class of 2020.

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.


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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