What Can Change In The Brain? Electrical Synapses, Research Shows

The brain's ability to reorganize itself - strengthening or weakening connections between neurons or adding or subtracting those connections - allows it to form memories, make transitions between sleep and waking, and focus attention on objects of interest.

This phenomenon is a form of neural plasticity. Chemical synapses, junctions where neurons communicate using chemical substances, have long been implicated in plasticity. Now, for the first time, Brown University scientists have demonstrated that electrical synapses are also subject to long-term changes in the brains of mammals. Their work appears in the journal Science.

"The fact that you can change the function of electrical synapses, and change them for longer than a few seconds, means that they may play a role in certain kinds of plasticity," said Barry Connors, a Brown professor of neuroscience and co-author of the paper.

"But plasticity governs many critical brain functions. Since electrical synapses help synchronize the activity of brain cells, these junctions probably help regulate specific brain rhythms that occur while you are awake or sleeping. So this work helps us better understand, in a basic sense, how the brain regulates behavioral states."

Carole Landisman, currently a neurobiology researcher at Harvard Medical School, is the lead author of the paper. Landisman was an investigator in Connors' lab at Brown, where the experiments were conducted.

To better understand how electrical synapses function, Landisman and Connors recorded activity from rat neurons that were connected by electrical synapses and stimulated other brain cells using brief bursts of electricity to see how the neurons would respond. They also treated neurons with two different drugs. All three techniques either activated or blocked metabotropic glutamate receptors or mGluRs, a type of neural trigger that responds to the amino acid glutamate, a trans-mitter molecule in the brain. The result: a long-lasting, 20 to 30 percent reduction in electrical synapse strength.

While previous studies have shown a related effect in the electrical synapses of goldfish, Landisman and Connors are the first to show that it also occurs in mammals.

"The change we describe here is similar to long-term mGluR depression at chemical synapses," Landisman said. "In both cases, communication between neurons is reduced."

The cells Landisman and Connors used in their experiments came from the thalamic reticular nucleus, a thin sheet of neurons that is part of the thalamus. The thalamus is a small region in the center of the brain responsible for relaying sensory information to the cerebral cortex, where it is transformed into memories and emotions, speech and movement.

The thalamic reticular nucleus' role as a sort of switch, starting or stopping the flow of sensory stimuli to the cortex, may implicate it as a major player in the regulation of sleep and wakefulness, the researchers said.

The pairs' work sheds important light on electrical synapses, which Connors' group discovered in the forebrains of mammals six years ago. The function and importance of these protein channels - which allow for lightening-quick signals to pass between neurons via ionic current - is only beginning to be understood. Last year, the Connors lab published research showing that electrical synapses help set the brain's master circadian clock.

The National Institutes of Health and the Eleanor and Miles Shore Scholars in Medicine Program funded the work.

Wendy Lawton
[email protected]
Brown University
brown.edu/Administration/News_Bureau

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