Insights & Outcomes: Place cells, planarians, and ‘prewet’ proteins
This month, Insights & Outcomes roams far and wide for the latest Yale research. We start in the hippocampus, then visit with worms, check out some noteworthy ion collisions, and finish up on the membrane of a cell.
‘Place cells’ go to town — and back
The hippocampus is a region of the brain that helps form long-term memories and plays a crucial role in helping us navigate the world. In a recent study, Yale researchers revealed just how it does this, enabling us to find our place in the world, recall location and direction, and finally even predict what we might find when we reach a new destination.
For the study, the lab of George Dragoi placed rats in a series of novel environments and then examined what happened to the neurons of the hippocampus over time. The experiments revealed the key role that so-called hippocampal “place cells” play in navigation across multiple environments.
The process, Dragoi said, can be understood by examining what happens to the brain of a tourist walking down New York’s 5th Avenue for the first time. As the tourist walks from downtown to midtown and back, those neurons known as place cells become active, depicting specific locations along the avenue. Intriguingly, most of these active neurons also pinpoint specific locations while walking back and forth on the other avenues parallel to 5th Avenue. But as the tourist turns to walk down one of the crosstown streets, either towards 4th Avenue or 6th Avenue, these particular hippocampal neurons cease to be active — they are orientated to the environment of 5th Avenue or avenues parallel to it. Instead, other neurons that had been quiet on 5th take over the spatial mapping and navigation as the tourist walks down the cross street.
In this scenario, during the maiden stroll down 5th Avenue, the tourist’s brain emphasizes speed rather than accuracy and does not record specific details of the environment. They are vaguely aware that sights observed along 42nd Street look different than those on 14th Street. But the more the tourist explores, the more the place cells are refined, which allows them to discriminate finer characteristics such as storefronts or subway stations that uniquely mark 5th Avenue.
Finally, as coordinated activity of this network of neurons recognizes that restaurants are found on avenues, the tourist will know that an intriguing Italian restaurant might be found if they walk down 3rd Avenue for the first time. “This generalization across the same orientation helps rapid navigation in novel but similar environments and helps us anticipate new experiences without confusion,” Dragoi said. The study was published in the journal Neuron.
Of proteins and planarians
Planarians are worms with an astounding capability — if they lose any part of their body, even their brain, they can grow back exact copies. Some strains can reproduce sexually, but others simply divide and create a duplicate worm. In either case they replace all cells of their body on a monthly basis.
“It’s difficult to talk about generations when you are dealing with planarians,” said Yale’s Josien van Wolfswinkel, assistant professor of molecular, cellular, and developmental biology.
The capacity of planarians and some animals like salamanders to regenerate seems to depend upon the presence of PIWI proteins, which are potent regulatory molecules that are usually only found in embryonic stem cells and in sex cells of animals. Most people thought the role of these proteins was limited to regulating these two types of cells.
However, in a recent study, van Wolfswinkel’s lab found PIWIs play a much larger role in planarians. These proteins, they discovered, are crucial to determining the fate of different cell types that emerge from stem cells. They do this by guarding against improper activation of transposons, or stretches of DNA that can replicate and move around the genome. If transposons are too close to areas of DNA which contain specific instructions to make specialized cell types, they can disrupt production of these newly differentiating cells.
“PIWI proteins help ensure that differentiated cells can be created without errors caused by proximity to transposons and therefore create healthy tissue,” van Wolfswinkel said. “It is possible that in other animals PIWI proteins are similarly required for the production of healthy new cells,” she said. The work was published in the journal Cell Reports.
The hunt continues for a physics phenomenon known as the “chiral magnetic effect” (CME).
Physicists from the international STAR Collaboration, based at Brookhaven National Laboratory’s Relativistic Heavy Ion Collider, have released the results of a blind analysis of how the strength of the magnetic field generated in certain ion collisions affects the particles streaming out.
They were hoping to find evidence of CME — an electric current generated along an external magnetic field, caused by a chiral imbalance (when mirror-image particles are not identical). The data did not detect CME, but researchers said the experiment yielded quite a bit of useful information.
“The results represent a significant milestone in our field,” said Helen Caines, a professor of physics at Yale and co-spokesperson for STAR. “We believe that they quite possibly represent the most precise heavy ion measurement ever done. We are certain that they will lead to a burst of theoretical activity.”
STAR’s search for the CME has strong ties to Yale. Jack Sandweiss, Alexei Chikanian, and Richard Majka, all now deceased, as well as former Yale researcher Evan Finch, who is now a faculty member at Southern Connecticut State University, spearheaded the original CME analyses for STAR.
Beneath the surface of ‘surface densities’
In a new study in the Proceedings of the National Academy of Sciences, Yale researchers Mason Rouches and Benjamin Machta, as well as University of Michigan researcher Sarah Veatch, look at a specific way that cell proteins signal each other.
Called “phase separation of proteins,” it is an active area of current research and refers to the way proteins sometimes separate into two distinct phases — much like the way oil and water separate after they are mixed.
“We examine what we term ‘surface densities’ — liquid-like assemblies of proteins found exclusively on the cell membrane,” said Rouches, a graduate student in molecular biophysics and biochemistry at Yale. “Our focus is on the subclass of proteins that phase-separate at cell membranes, often aiding in signaling.”
Rouches and Machta argue that these surface densities are prewet — a technical term used in physics. A prewet ‘phase’ would be, for example, a molecularly thin, two-dimensional film of liquid that forms on the surface of a system whose bulk is in a three-dimensional gas phase.
In this case, proteins are stabilized as droplet-like films at the membrane surface. “We find that phase-separation in the membrane encourages the phase separation of proteins at the cell surface, and that proteins likewise encourage phase separation of lipids in the membrane, reinforcing each other in a single surface phase,” said Machta, an assistant professor of physics in Yale’s Faculty of Arts and Sciences and a member of the Systems Biology Institute at West Campus.
The research offers insight into mechanisms of signaling cluster formation — for example, the clusters that form in T-cells upon engagement with a foreign antigen — and of long-lived protein assemblies found in the synapses of neurons and other cell types.