Marder, Shatz, and Merzenich share 2016 Kavli Prize in Neuroscience

Eve MarderBreaking news: The 2016 Kavli Prize in Neuroscience is awarded to Eve Marder (Brandeis), Carla Shatz (Stanford), and Michael M. Merzenich (UCSF), “for the discovery of mechanisms that allow experience and neural activity to remodel brain function.”

 

Trapping individual cell types in the mouse brain

Lines labeling cortical subplate, mesencephalic, and diencephalic cell types

Lines labeling cortical subplate, mesencephalic, and diencephalic cell types (see Fig. 7 in Shima et al.)

The complexity of the human brain depends upon the many thousands of individual types of nerve cells it contains. Even the much simpler mouse brain probably contains 10,000 or more different neuronal cell types. Brandeis scientists Yasu Shima, Sacha Nelson and colleagues report in the journal eLife on a new approach for genetically identifying and manipulating these cell types.

Cells in the brain have different functions and therefore express different genes. Important instructions for which genes to express, in which cell types, lie not only in the genes themselves, but in small pieces of DNA called enhancers found in the large spaces between genes. The Brandeis group has found a way to highjack these instructions to express other artificial genes in particular cell types in the mouse brain. Some of these artificially expressed genes (also called transgenes) simply make the cells fluorescent so they can be seen under the microscope. Other transgenes are master regulators that can be used to turn on or off any other gene of interest. This will allow scientists to activate or deactivate the cells to see how they alter behavior, or to study the function of specific genes by altering them only in some cell types without altering them everywhere in the body. In addition to developing the approach, the Brandeis group created a resource of over 150 strains of mice in which different brain cell types can be studied.

website: enhancertrap.bio.brandeis.edu

Shima Y, Sugino K, Hempel C, Shima M, Taneja P, Bullis JB, Mehta S, Lois C, Nelson SB. A mammalian enhancer trap resource for discovering and manipulating neuronal cell types. eLife. 2016;5.

Simons Foundation funds Brandeis Math, Physics collaborations

In 2014, the Simons Foundation, one of the world’s largest and most prominent basic science philanthropies, launched an unprecedented program to fund multi-year, international research collaborations in mathematics and theoretical physics. These are $10M grants over four years, renewable, that aim to drive progress on fundamental scientific questions of major importance in mathematics, theoretical physics, and theoretical computer science. There were 82 proposals in this first round. In September 2015, two were funded. Both involve Brandeis.

Matthew Headrick (Physics) is deputy director of the Simons Collaboration It from Qubit, which involves 16 faculty members at 15 institutions in six countries. This project is trying from multiple angles to bring together physics and quantum information theory, and show how some fundamental physical phenomena (spacetime, black holes etc.) emerge from the very nature of quantum information. Fundamental physics and quantum information theory remain distinct disciplines and communities, separated by significant barriers to communication and collaboration. “It from Qubit” is a large-scale effort by some of the leading researchers in both communities to foster communication, education and collaboration between them, thereby advancing both fields and ultimately solving some of the deepest problems in physics. The overarching scientific questions motivating the Collaboration include:

  • Does spacetime emerge from entanglement?
  • Do black holes have interiors?
  • Does the universe exist outside our horizon?
  • What is the information-theoretic structure of quantum field theories?
  • Can quantum computers simulate all physical phenomena?
  • How does quantum information flow in time?

Bong Lian (Mathematics) is a member of the Simons Collaboration on Homological Mirror Symmetry, which involves nine investigators from eight different institutions in three countries. Mirror Symmetry, first discovered by theoretical physicists in late ‘80s, is a relationship between two very different-looking physical models of Nature, a remarkable equivalence or “duality” between different versions of a particular species of multidimensional space or shape (Calabi-Yau manifolds) that seemed to give rise to the same physics. People have been trying to give a precise and general mathematical description of this mirroring ever since, and in the process have generated a long list of very surprising and far-reaching mathematical predictions and conjectures. The so-called “Homological Mirror Symmetry Conjecture” (HMS) may be thought of as a culmination of these efforts, and Lian was a member of the group (including S.-T. Yau) that gave a proof of a precursor to HMS in a series of papers in the late ‘90s.

Lian and his Simons collaborators are determined to prove HMS in full generality and explore its applications. One consequence of HMS says that if one starts from a “complex manifold” (a type of even-dimensioned space that geometers have been studying since Riemann described the first examples in 1845), then all its internal geometric structures can in fact be described using a certain partner space, called a “symplectic manifold”. The latter type of space was a mathematical edifice invented to understand classical physics in the mid-1900s. This connection goes both ways: any internal geometric structure of the symplectic partner also has an equally compelling description using the original complex partner. No one had even remotely expected such a connection, especially given that the discoveries of the two types of spaces — complex and symplectic — were separated by more than 100 years and were invented for very different reasons. If proven true, HMS will give us ways to answer questions about the internal geometric structure of a complex manifold by studying its symplectic partner, and vice versa.

Proving HMS will also help resolve many very difficult problems in enumerative geometry that for more than a century were thought to be intractable. Enumerative geometry is an ancient (and until recently moribund) branch of geometry in which people count the number of geometric objects of a particular type that can be contained inside a space. Mirror symmetry and HMS have turned enumerative geometry into a new way to characterize and relate shapes and spaces.

Fruit flies alter their sleep to beat the heat

Do you have trouble sleeping at night in the summer when it is really hot?

Does a warm sunny day make you want to take a nap?

You are not alone — fruit flies also experience changes in their sleep patterns when ambient temperature is high. In a new paper in Current Biology, research scientist Katherine Parisky and her co-workers from the Griffith lab show that hot temperatures cause animals to sleep more during the day and less at night, and then investigate the mechanisms governing the behavior.

The increase in daytime sleep is caused by a complex interplay between light and the circadian clock. The balance between daytime gains and nighttime losses at high temperatures is also influenced by homeostatic processes that work to keep total daily sleep amounts constant. This study shows how the nervous system deals with changes caused by environmental conditions to maintain normal operations.

Parisky KM, Agosto Rivera JL, Donelson NC, Kotecha S, Griffith LC. Reorganization of Sleep by Temperature in Drosophila Requires Light, the Homeostat, and the Circadian Clock. Curr Biol. 2016.

Acid, Base and Electrical Charge at the Water Surface

Liquid water seems simple, but there’s a lot of chemistry going on in it.
It is common knowledge that, in pure water, under ordinary conditions, 1 in every 10 million H2O molecules is dissociated into the acid ion H+ and the base ion OH. However, what preference, if any, these self-ions of water have to sit at the air water interface has been the subject of lengthy and heated debate. The question is consequential in a wide range of contexts, including on the surface of droplets in the atmosphere and at the surfaces of biomolecules.  The Herzfeld group has now bridged the gap between experiment and theory by using a model that efficiently balances three subtle features of water molecules (polarizability, H+ sharing, and H+ transfer) that control the ambient behavior of the liquid. The model predicts that OH– prefers the air-water interface while H+ avoids it, consistent with observations of the response of air bubbles in water to an applied electric field.
water
Bai C, Herzfeld J. Surface Propensities of the Self-Ions of Water. ACS Central Science. 2016.

Sleep suppresses brain rebalancing

Why humans and other animals sleep is one of the remaining deep mysteries of physiology. One prominent theory in neuroscience is that sleep is when the brain replays memories “offline” to better encode them (“memory consolidation”). A prominent and competing theory is that sleep is important for re-balancing activity in brain networks that have been perturbed during learning while awake. Such “rebalancing” of brain activity involves homeostatic plasticity mechanisms that were first discovered at Brandeis University, and have been thoroughly studied by a number of Brandeis labs including the Turrigiano lab. Now, a study from the Turrigiano lab just published in the journal Cell shows that these homeostatic mechanisms are indeed gated by sleep and wake, but in the opposite direction from that theorized previously: homeostatic brain rebalancing occurs exclusively when animals are awake, and is suppressed by sleep. These findings raise the intriguing possibility that different forms of brain plasticity – for example those involved in memory consolidation and those involved in homeostatic rebalancing – must be temporally segregated from each other to prevent interference.

sleeprats

The requirement that neurons carefully maintain an average firing rate, much like the thermostat in a house senses and maintains temperature, has long been suggested by computational work. Without homeostatic (“thermostat-like”) control of firing rates, models of neural networks cannot learn and drift into states of epilepsy-like saturation or complete quiescence. Much of the work in discovering and describing candidate mechanisms continues to be conducted at Brandeis. In 2013, the Turrigiano Lab provided the first ­in vivo evidence for firing rate homeostasis in the mammalian brain: lab members recorded the activity of individual neurons in the visual cortex of freely behaving rat pups for 8h per day across a nine-day period during which vision through one eye was occluded. The activity of neurons initially dropped, but over the next 4 days, firing rates came back to basal levels despite the visual occlusion. In essence, these experiments confirmed what had long been suspected – the activity of neurons in intact brains is indeed homeostatically governed.

Due to the unique opportunity to study a fundamental mechanism of brain plasticity in an unrestrained animal, the lab has been probing the possibility of an intersection between an animal’s behavior and homeostatic plasticity. In order to truly evaluate possible circadian and behavioral influences on neuronal homeostasis, it was necessary to capture the entire 9-day experiment, rather than evaluate snapshots of each day. For this work, the Turrigiano Lab had to find creative computational solutions to recording many terabytes of data necessary to follow the activity of single neurons without interruption for more than 200 hours. Ultimately, these data revealed that the homeostatic regulation of neuronal activity in the cortex is gated by sleep and wake states. In a surprising and unpredicted twist, the homeostatic recovery of activity occurred almost exclusively during periods of activity and was inhibited during sleep. Prior predictions either assumed no role for behavioral state, or that sleeping would account for homeostasis. Finally, the lab established evidence for a causal role for active waking by artificially enhancing natural waking periods during the homeostatic rebound. When animals were kept awake, homeostatic plasticity was further enhanced.

This finding opens doors onto a new field of understanding the behavioral, environmental, and circadian influences on homeostatic plasticity mechanisms in the brain. Some of the key questions that immediately beg to be answered include:

  • What it is about sleep that precludes the expression of homeostatic plasticity?
  • How is it possible that mechanisms requiring complex patterns of transcription, translation, trafficking, and modification can be modulated on the short timescales of behavioral state-transitions in rodents?
  • And finally, how generalizable is this finding? As homeostasis is bidirectional, does a shift in the opposite direction similarly require wake or does the change in sign allow for new rules in expression?

Authors on the paper include postdoctoral fellow Keith Hengen, Neuroscience grad student Alejandro Torrado Pachedo, and Neuroscience undergraduate James McGregor ’14 (now in grad school at Emory).

Hengen KB, Torrado Pacheco A, McGregor JN, Van Hooser SD, Turrigiano GG. Neuronal Firing Rate Homeostasis is Inhibited by Sleep and Promoted by Wake. Cell. 2016.

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