An article published in Proceedings of the National Academy of Sciences provides strong evidence for a novel type of communication between nerve cells in the brain.
The findings may have relevance for the prevention and treatment of epilepsy, and possibly in the exploration of other aspects of brain functions, from creative thought processes to mental illnesses such as schizophrenia.
The work was performed jointly by scientists at SUNY Downstate Medical Center in Brooklyn, New York; Colorado State University in Fort Collins, Colorado; Mount Sinai School of Medicine in Manhattan, New York; and the University of Newcastle in the United Kingdom. The lead author was Dr. Farid Hamzei-Sichani, an MD/PhD student at Downstate Medical Center, working in the laboratory of Roger Traub, MD, professor of physiology and pharmacology and of neurology at SUNY Downstate.
Epilepsy a group of disorders characterized by the recurrent occurrence of spontaneous seizures affects roughly one-half of one percent of the U.S. population, and a higher percentage still in developing countries. In approximately one-third of patients, seizures are not properly controlled by available treatments. Problems can arise in the ability of patients to function at home and in society.
Epileptic seizures are customarily regarded to reflect an imbalance between the ability of nerve cells to excite one another, on the one hand, and to inhibit one another, on the other hand. The excitation and inhibition take place because the activity of nerve cells leads to the release of particular chemicals called neurotransmitters at specialized junctions that are called chemical synapses. The neurotransmitters diffuse across a tiny space between the nerve cells, and then bind to proteins (called receptors) on other nerve cells. Binding of a neurotransmitter to a receptor in turn causes excitation or inhibition in the other nerve cells.
This is the classic means of communication between nerve cells, and lies at the base of most of current understanding of how the brain processes information and controls muscles in the body.* A seizure is presumed to occur when there is too much chemical synaptic excitation, and/or not enough inhibition.
There is, however, another means for nerve cells to communicate with one another, called gap junctions. Gap junctions allow electric current to flow directly from one cell to another, without involving the release and diffusion of transmitter chemicals, and may be thought of as 'short circuits linking or cutting across the pathways through which cells normally communicate.
Gap junctions are found in many parts of the body, such as the heart. Gap junctions between nerve cells have been most studied in older vertebrates (such as fish) and in invertebrates (such as leeches and crabs); additionally, gap junctions in mammals have been studied that exist between nerve cells that produce inhibition that is, between cells that are not primarily involved in epileptic seizures. Gap junctions between excitatory cells in the mammalian brain have not traditionally been part of the thinking of neuroscientists.
One source of the idea that gap junctions were vitally important in epilepsy came from observations of brain waves that are recorded just before a seizure begins: these waves can occur at very high frequencies, 100 times per second or even more. That observation, and other experiments performed in Europe starting 10 years ago, led one of the authors of the PNAS article (Roger Traub, at SUNY Downstate) to propose a novel hypothesis: that excitatory nerve cells the cells most critical in the generation of epileptic seizures are also coupled together by gap junctions; that is, gap junctions are not confined to the cells that produce inhibition. Furthermore, gap junctions between excitatory cells were predicted to occur at an unexpected place: the axons of the cells (the axon is the part of the cell that allows propagation of a signal over long distances).