Memories May Be Made Of Clusters Of Proteins In A Certain Type Of Neuron

NEW YORK, Oct. 18, 2001—A new type of structural change that occurs when brain cells communicate with each other during what is believed to be the creation of memory and learning has been identified by researchers at Columbia University College of Physicians & Surgeons. Led by Dr. Robert Hawkins, associate professor of clinical neurobiology and behavior (in psychiatry), Columbia investigators, including Nobelist Eric Kandel and colleagues, have found for the first time rapid changes in the way certain proteins cluster in the pre-synaptic neurons in what is called long-term potentiation. Long-term potentiation is the increase of the strength of a synapse in a process associated with memory formation. A synapse consists of a pre-synaptic neuron that releases certain chemicals called neurotransmitters that act on cell surface receptors in the post-synaptic neuron to create nerve transmission. While most research has focused on alterations to the post-synaptic neuron as the locale for long-term potentiation, Columbia researchers now have the first evidence of rapid structural changes in the pre-synaptic neuron as another site for the laying down of memory pathways in the brain. “This is the first evidence of rapid structural changes to the pre-synaptic neuron that are associated with long-term potentiation,” says Dr. Hawkins. Their findings are being published by Science on Oct. 18 on the Science Express website. In the research, the investigators studied what are called “primary synaptic vesicle-associated proteins” in the pre-synaptic neurons of cultured mouse hippocampus cells. The hippocampus is a region in the brain where neuroscientists believe memories are stored. These proteins help form the bubble-like structures inside the neuron that carry neurotransmitters to the surface of the neuron for the release into the synapse. Using fluorescent-labeled antibodies, the researchers found that within minutes of long-term potentiation, these vesicle-associated proteins in the pre-synaptic neurons clustered together. The next step in the research is to understand how these early changes might relate to the formation of memories. Most neuroscientists think that long-term potentiation lasting more than a couple of hours involves the growth of new synapses, which means alterations to both the pre- and post-synaptic neurons. Columbia researchers are trying to find out if changes happen first on one side of the synapse that then cause changes on the other side. Most recent research has focused on post-synaptic changes with some investigators suggesting that changes in the pre-synaptic neurons are passive consequences. “Our research indicates that pre-synaptic changes occur surprisingly rapidly and could precede and even initiate some of the post-synaptic changes,” Dr. Hawkins says. “My own view is that there is probably a fairly elaborate dance with the two partners exchanging signals in both directions so they end up making matching parts of a whole synapse. This is what has been seen at the neuromuscular junction [the site of the transmission of neural impulses and muscle], where these questions have been studied much more extensively.”

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