Rat neuron injection lets mice that can’t smell sniff out cookies

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The hippocampus in a mouse brain that contains some rat cells (red)

M. Khadeesh Imtiaz/Columbia University Irving Medical Center (CC BY-NC-ND)

Rat cells grown inside the brains of mice with no sense of smell have allowed them to gain the ability. This is the first time that an organism of one species has experienced the world through the sensory neurons of another.

When cells from one species are grown in the body of another, the resulting organism is known as an interspecies chimera. These have previously been used for research into certain tissues, such as in mice that contain cells of the human immune system to study disease responses. But creating chimeras for other tissues, like neural tissue, is more complex.

Researchers at the University of Texas Southwestern Medical Center previously grew mice with partial rats’ brains. Now, another team has shown that this interspecies chimerism can give mice the ability to smell after they were genetically modified to lack the neurons for picking up scents.

Kristin Baldwin at Columbia University in New York and her colleagues injected rat stem cells into the embryos of these modified mice. Once the embryos were adult mice, the researchers monitored the activity of their neurons. They found that the animals had functional neural pathways for sensing smell that were composed of both rat and mouse cells that could communicate directly with one another.

When the researchers tested the sense of smell in these mice by having them search for hidden mini Oreo cookies, they found those that had received the stem-cell injection were able to easily find the food, in contrast to mice with the same genetic modification that weren’t chimeras.

“This has a great opportunity for human health, where we can understand better how to make cell replacement therapies for humans,” says Baldwin. “We can also make models in a mouse or rat of diseases that affect longer-lived organisms.”

The fact that the rat cells were able to promote food-seeking in mice that would otherwise have lacked a sense of smell is very impressive, says Walter Low at the University of Minnesota. “Now, whether this same kind of thing can occur in more disparate species remains to be determined, but at least [this study] shows what’s happening in two species that are relatively close [in evolutionary terms],” he says.

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