This week’s papers from Boston labs

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Play restores memory in brain-damaged mice

Mice with Alzheimer’s disease-like brain damage recovered long-term memory after playing and exercising in special cages filled with toys, according to a new study. MIT researchers found that the mice formed new connections between their surviving neurons in response to environmental stimulation.

The work, published online in Nature earlier this week, suggests that in neurodegenerative diseases like Alzheimer’s, memories may be inaccessible but not totally erased, and so may be reawakened under the right conditions.

Researchers have known that enriching the normally spare accommodations of healthy laboratory mice improved their ability to learn and remember. But Li-Huei Tsai and colleagues wanted to know if the same held true for brain-damaged mice.

To answer that question, the MIT team engineered mice with a gene for a protein toxic to brain cells. Before “switching on” that gene, the researchers trained the mice to associate a certain cage with a mild electric shock to one of their feet, a conditioning technique that forms a long-term memory and causes the mice to act fearful whenever they encounter the same cage.

When neurodegeneration set in, the mice lost their fear of the shocking surroundings, indicating that the memory of the shocks was lost. But after a month in the toy-filled cage, the animals once again showed fear when placed in the box.

Further experiments indicated that environmental enrichment worked to bring memories back by strengthening the connections between remaining neurons.

The researchers identified two chemical compounds that mimicked the effects of enrichment on memory in the mice. More work is needed to see whether more fun and games, or a pill, can bring memories back for humans. Pat McCaffrey

Prototype PCR machine gets small and fast

A cheap, pocket-sized device can quickly replicate DNA using polymerase chain reactions (PCR), a new study shows. The researchers hope the device, which runs on two AA batteries, could make PCR, a basic tool in molecular biology, more available in the field or in developing countries.

The prototype, developed by Nitin Agrawal of the Center for Engineering in Medicine at Massachusetts General Hospital, along with colleagues, takes advantage of the principle of convection to make a smaller, faster, and more energy-efficient PCR device.

This PCR device cost just $10 to make and can fit in your pocket. (Credit: Victor Ugaz)

In typical PCR machines, small test tubes containing DNA samples are inserted into a metal block. As the block is heated and cooled, the samples reach the three different temperatures needed for PCR to take place.

The new device consists of three small metal cylinders placed side by side, each heated to a different temperature. The device circulates the DNA sample through a continuous line of tubing wrapped around these blocks. As heat is applied, convection causes the fluid to flow through the tubing. Each cylinder brings the fluid passing by to its respective temperature, producing the necessary reactions.

Because the device keeps the temperature of the individual blocks constant, and the fluid continuously moves through the tube, the reactions for each temperature cycle take only seconds rather than minutes to occur. The researchers showed that the device—which costs about $10 in parts, including the batteries—could replicate DNA as precisely as more expensive machines and reduce the total reaction time from a couple of hours to as little as 20 minutes.

The research was published this week in Angewandte Chemie International Edition. Mason Inman

Neurons branch out by avoiding their own

Brain cells that process sensory information have extensive branches, known as dendrites, that fan out to form elaborate neural circuits. How a neuron sends out dozens of branches that evenly blanket a target area in an organized way, without getting tangled up with each other, has been a mystery.

Work from the lab of Dietmar Schmucker and colleagues at the Dana-Farber Cancer Institute sheds some light on this process. In a paper in this week’s Neuron_, the researchers showed that in fruit flies, dendrites organize themselves using special proteins located on their outer surface. These proteins enable the dendrites to detect and repel others emanating from the same neuron. Two papers from other labs independently reported similar findings, one in the same issue of Neuron and one in this week’s "_Cell":https://www.cell.com/content/article/abstract?uid=PIIS0092867407004709.

The gene for the protein, called DSCAM (Down’s syndrome cell adhesion molecule), is striking because it has the potential to produce 38,016 different versions of the protein. Each version can adhere to itself, but not with any other version. The researchers showed that dendrites with the same form of DSCAM on their surface recognized and then repelled each other, ultimately forming nonoverlapping patterns. Inactivation of the DSCAM gene in single neurons in flies led to dendrite disorganization, with branches that were tangled and overlapping.

The unusually large number of DSCAM versions may allow neurons to keep their own branches organized among the complex web of dendrites from multiple cells. Pat McCaffrey