Signaling Neurons Make Neighbor Cells "Want In"

Synapses are primed to strengthen (and thus enable learning) if a nearby one has just been stimulated















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HELP THY NEIGHBOR: When an electrical signal crosses a synapse, the spines strengthen, enabling better communication. A residual effect, however, has now been found to aid in strengthening neighboring synapses, as well. Image: © ISTOCKPHOTO/SEBASTIAN KAULITZKI

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A new discovery about the function of neurons could help scientists understand how the brain assembles information during learning and memory formation.

Scientists have found that when electrical impulses are passed from one neuron to another, they not only strengthen the synapse (connection) between them, but they also give a boost to neighboring synapses, priming them to learn more quickly and easily. Researchers report in Nature that the extra kick, which lasts from five to 10 minutes, may be key to memory formation.

The residual effect "had been predicted based on so-called classic models of plasticity"—the ability of the brain to adapt by strengthening or weakening connections between neurons—but had not previously been proved, says study co-author Karel Svoboda, a biophysics group leader at the Howard Hughes Medical Institute's Janelia Farm Research Campus in Ashburn, Va. "You'd like to have clustered plasticity of this sort" to keep memories grouped together.

Neurons, or nerve cells, each have a pair of projections—the axon and the dendrite, which transmit and receive impulses, respectively. The dendrite, a treelike structure, has several branches dotted with hundreds synaptic receiving terminals called "spines," each connected to the axons of scores of other neurons. When one of these spines receives stimulation (through the synapse it creates with another cell's axonal projection), the spine expands into the synapse, strengthening the link between its neuron and the other cell. This process of enhanced communication through a synapse is called long-term potentiation (LTP) and is thought to be the basis of learning.

Previous attempts to identify this process were stymied by inexact methods. Researchers primarily used electrical impulses, which do not allow for good spatial observation. Svoboda and study co-author Christopher Harvey, a graduate student in Svoboda's lab, used a more precise technique. They attached a light-absorbing chemical group to the neurotransmitter glutamate (an excitatory chemical messenger in the brain) at a particular synapse in a slice of a rat's hippocampus, the brain region responsible for short-term memory. When they trained a laser on the glutamate, it was freed from its light-absorbing molecular captor and thereby able to resume its function; it went to the dendritic spine in the synapse, allowing ions to enter the cell and an electrical signal to be generated.

As a result of this stimulation, the spine stretched farther into the synapse. Researchers did not find any evidence that neighboring spines had also expanded, but they did find that it took less stimulation—only 20 percent of the original prodding—to prompt any of the 20 spines within 10 microns (around four ten-thousandths of an inch) to undergo LTP. This effect appeared to last for five to 10 minutes, the scientists report.

Svoboda says that this cooperative activity may underlie how information is integrated when, for instance, an individual enters a new environment and looks around making associations of different cues within that space. "People didn't know how these associations over the course of 10 minutes or so could be coded in neurons," he says. "It provides a possible mechanism for associations over minutes."

In an editorial accompanying the article, Bernardo Sabatini, an assistant professor of neurobiology at Harvard Medical School, says that Harvey and Svoboda's work introduces new complexity into the brain's neuronal wiring.

"[For] some forms of activity-dependent plasticity in the hippocampus, the fundamental unit of regulation might be larger than an individual synapse," he wrote, "and, rather, a physically clustered cohort of synapses with similar firing patterns, whose spatial arrangement on dendrites arises naturally follow mutually reinforcing interactions between synapses."



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