Salk Institute teams gain insight into how synapses separate important neural messages from background noise.

When neurons communicate, they send messages across a junction known as a synapse. Synapses don’t act as passive channels for the brain’s messages—they actively filter them, amplifying important messages while eliminating extraneous background noise. 

“Synapses, by their nature, are probabilistic little devices,” said Vitaly Klyachko, a neurobiologist at the Salk Institute in Southern California. “They don’t transfer every type of information they receive.”

In fact, only 10 to 25% of the signals that a neuron receives will be transmitted across the synapse; the rest are “dropped” much like a cell phone call.

New research led by Klyachko and Salk colleague Charles Stevens demonstrates one mechanism by which synapses separate the good stuff from the junk. 

The Salk researchers focused on a circuit that helps animals navigate through space and resides in the hippocampus—the large brain structure involved in learning and memory. They began by extracting and isolating neurons in this circuit from slices of rat hippocampus. Then, they administered electric signals to the neurons in a pattern that mirrored the electrical signals a rat’s neurons would receive as it explored a new environment.

Klyachko and Stevens discovered commonalities in the messages that were successfully relayed across the synapse. In a rat’s hippocampus, information about place is relayed in short bursts of high frequency electrical signals. These bursts were the inputs most reliably relayed across the synapse. Not only were such signals successfully transmitted, but they were actually amplified, becoming even stronger in the post-synaptic neuron.

“Things associated with information, which are bursts, are getting enhanced very strongly,” said Klyachko, whose findings appear in the July issue of PLoS Biology. “Synapses can sense them and enhance their ability to transmit.”

On the other hand, when neurons received widely spaced, infrequent electrical signals—which in the rat hippocampus are thought to correspond to quiet periods of relative inactivity—far fewer messages were relayed, Klyachko said. This finding indicates that synapses in this circuit are able to recognize high frequency bursts as more important signals and are able to improve their reliability in transmitting such impulses.

Many previous attempts to characterize how synapses work have been conducted at room temperature and produced data with few obvious patterns. Klyachko’s breakthrough came when he decided to conduct his experiment near the temperature at which the neurons actually work in the body.

“The circuit works somewhat differently from the way we thought,” said Robert Zucker, a neurobiologist at the University of California, Berkeley, commenting on the study. “If you look at the same experiments at room temperature, you don’t see the same trends. This is much clearer in terms of what seems to be going on. The synapse selects certain frequencies that are naturally present during behavior, transmits that information effectively and suppresses the rest.”

The researchers also found that excitatory synapses, which facilitate signal transmission, and inhibitory synapses, which stifle it, actually work together in helping these important messages to be transferred. While a high frequency burst prompts the excitatory synapse to enhance its ability to transmit information, it simultaneously weakens the effect of the inhibitory synapse. Rather than working against each other, the synapses work together, like two volume controls of the same amplifier, Klyachko said.

Klyachko acknowledges that his study examined only one circuit in one brain structure, and that all synapses may not work in exactly the same way.

“It will require very complex recordings from the whole brain to make sure this is the case in the whole brain,” Klyachko said. “But it’s very curious the way things are tuned.”

Originally published July 4, 2006

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