Neural Stem Cells in the Hypothalamus Shown to Control Rate of Aging in Mice

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Scientists find brain cells that know which end is up

People are intuitive physicists, knowing from birth how objects under the influence of gravity are likely to fall, topple or roll. In a new study, scientists have found the brain cells apparently responsible for this innate wisdom.

In a part of the brain responsible for recognizing color, texture and shape, Johns Hopkins University researchers found neurons that used large-scale environmental cues to infer the direction of gravity. The findings, forthcoming this month in the journal Current Biology, and just posted online, suggest these cells help humans orient themselves and predict how objects will behave.

“Gravity is a strong ubiquitous force in our world,” said senior author Charles E. Connor, a professor of neuroscience and director of the university’s Zanvyl Krieger Mind/Brain Institute. “Our results show how the direction of gravity can be derived from visual cues, providing critical information about object physics as well as additional cues for maintaining posture and balance.”

Connor, along with lead author Siavash Vaziri, a former Johns Hopkins postdoctoral fellow, studied individual cells in the object area of the rhesus monkey brain, a remarkably close model for the organization and function of human vision. They measured responses of each cell to about 500 abstract three-dimensional shapes presented on a computer monitor. The shapes ranged from small objects to large landscapes and interiors.

They found that a given cell would respond to many different stimuli, especially large planes and sharp, extended edges. What tied these stimuli together was their alignment in the same tilted rectilinear reference frame. These cells, sensitive to different tilts, could provide a continuous signal for the direction of gravity, even as a person constantly moves.

In other words, Connor said, these neurons could help people understand which way is up.

“The world does not appear to rotate when the head tilts left or right or gaze tilts up or down, even though the visual image changes dramatically,” he said. “That perceptual stability must depend on signals like these that provide a constant sense of how the visual environment is oriented.”

The researchers’ initial discovery of cells sensitive to large-scale shape, reported in Neuron in 2014, was surprising because they found them in a brain region long regarded as dedicated exclusively to object vision. The new findings make sense of this anatomical juxtaposition, since knowing the gravitational reference frame is critical for predicting how objects will behave.

“When we dive after a ball in tennis, the whole visual world tilts, but we maintain our sense of how the ball will fall and how to aim our next shot,” Connor said. “The visual cortex generates an incredibly rich understanding of object structure, materials, strength, elasticity, balance, and movement potential. These are the things that make us such expert intuitive physicists.”

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Thermal microscopy of single cells

Thermal properties of cells regulate their ability to store, transport or exchange heat with their environment. So gaining control of these properties is of great interest for optimizing cryopreservation — the process of freezing and storing blood or tissues, which is also used when transporting organs for transplants.

Cell activity influences thermal properties, and at the tissue level this explains why infected wounds feel warm to the touch. Cancer cells, in particular, contain a thermal signature that reflects a higher metabolism than those of healthy cells. This feature is useful for grading tumors and can be used to complement classical histological analysis.

A team of researchers in France working within this realm wondered whether it might be possible to tap into active thermography camera technology — behind night-vision equipment and the thermal imaging of buildings — to create a sort of thermal microscope to produce heat maps of single cells to help them understand the thermal behavior of the cells or go a step even further by detecting diseased conditions at the sub-cell scale.

As the team led by the University of Bordeaux reports in the journal Applied Physics Letters, from AIP Publishing, the first step of their work involved growing cells atop a nanometric titanium sheet. Titanium was selected because it’s the main constituent of bone implants.

“We flash heat the titanium sheet by only a few degrees with a micrometric laser spot,” explained Thomas Dehoux, a researcher at CNRS, the French National Centre for Scientific Research. “You might say we ‘heat the spot’ to image the temperature variations on the bottom side of the sheet. If there is no cell on the other side, the heat remains in the titanium sheet and the temperature increases.” Conversely, if there is a cell on the other side it will absorb heat and create a cold spot on the sheet.

The temperature variations involved are quite small and occur on a tiny micron-sized spot — a hundredth of a human hair — so the researchers can’t rely on a standard thermometer. Instead, they measure the titanium sheet’s ‘bulging’ upon heating.

What exactly do they look for? “When the temperature is high — without a cell on the other side — the metal sheet dilates locally and creates a bump,” said Dehoux. “When the temperature decreases — a cell is probed — the sheet’s profile returns to normal. We’re able to detect this effect with a second laser beam that’s deflected by the movement of the bottom surface, which gives us unprecedented sensitivity.”

Each part of the cell absorbs heat differently, thanks to the inhomogeneities in its thermal properties. “This allows us to see through the metal sheet and produce a thermal image of the cell,” he added.

While many existing modalities exploit differences in optical properties to image cells, most use fluorescent marking to increase contrast. Such images reveal the structure and molecular composition of the cell, but provide no useful details about its thermal properties.

The significance of the team’s model is that it provides an image of a single cell with micrometer resolution via a contrast based on the cell’s thermal properties. “Before now, no such image has ever been produced — it’s like looking at cells with night-vision goggles,” pointed out Dehoux.

In terms of applications, the team hopes their technique can serve as a new tool to perform histological analysis and detect diseased cells within samples of patients’ tissue. “It might also reveal new information about the behavior of cells because we will be able to observe them with a new contrast,” said Dehoux.

What’s next for the team? Since this is the first time images of this nature have been produced, the technique could use a bit more optimization. “In particular, we want to improve its acquisition time and sensitivity to enable observation of cells in real time,” Dehoux noted. “We’d also like to test the effect of anti-cancer drugs on the thermal properties of cells to see if new thermal strategies can be defined to stop cancer.”

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