When cells go quiet

Inside the brain, communication breakdown is a nervous breakdown

For a nerve cell, it’s all about making connections and dropping the duds. Harvard neuroscientist Jeff Lichtman has been keeping an eye on nerve networking by observing how one neuron reacts when another grows silent. In a phone interview, he described the situation by analogy: “It’s like if I’m talking to you and you stop talking back to me. After a while I’ll hang up and walk away.”

NEURAL NETWORKING By watching nerve cells in the brain, a team monitors changes in the connections between nerve cells from the brain stem (stained yellow in image) of a living mouse and nerve cells near the salivary gland (stained blue). If one cell drops communication, the connection eventually breaks. C.M. McCann and J.W. Lichtman

Nerve cells grown in petri dishes are known to act this way — abandoning cells that ignore the chemical messages they send.

But now Lichtman and his colleagues, reporting online June 22 in Nature Neuroscience, document the phenomenon in a living animal, using a technique that allowed them to watch cells grow and change in real time.

The team shows how nerve cells from the brain stem (stained yellow in image) of a living mouse make connections with nerve cells (stained blue) near the salivary gland.

When the team injured the blue-stained cells, rendering them mute, the yellow-stained neurons first stopped sending chemical signals and, over time, pulled back. “Literally,” Lichtman says, “we watched connections get weak and disappear.”

Throughout life, connections are made and subsequently lost. Pruning unnecessary connections is an essential part of precise wiring, Lichtman says.

Doctors test the “wiring” in their patients’ nervous systems by tapping knees, expecting the strike to signal the brain and the brain to wire back down a “kick” response to the leg. In this study, the team examined salivary connections — the type that make animals drool at the scent of something scrumptious. They weren’t interested in salivation per se, but rather in understanding how neural connections are molded as an animal grows and experiences life. This malleable process, called synaptic plasticity (synapses are the places where two nerve cells meet), occurs throughout the brain. For example, in the hippocampus, memories form as connections are strengthened and may be lost when connections diminish.

“This is a terrific study because they watched real things in a real animal, in real time,” comments Darwin Berg, a neuroscientist at the University of California, San Diego. “These mechanisms are almost certainly employed in other systems such as learning and memory.”

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