Understanding biochemical mechanisms associated with memory formation

A discovery by a research team led by Dr. Ryohei Yasuda at the Max Planck Florida Institute for Neuroscience has significantly advanced basic understanding of biochemical mechanisms associated with how memories are formed.

The surprising results of the team's research were published Nov. 29 in the research journal Science.

The research focused on the communication between synapses and the nucleus of a neuron, specifically the mechanisms by which signaling initiated at synapses is transmitted into the nucleus to induce chemical changes.

Because the number of neurons in the adult brain does not increase significantly with age, neurobiologists believe that memories are not formed by new neuron production, but by a strengthening of the connections between existing neurons to improve the effectiveness of their communication. This process of synaptic strengthening is known as long-term potentiation (LTP) and is thought to result in the storage of information.

LTP is one of several phenomena underlying synaptic plasticity, the ability of chemical synapses to change their strength. Memories are thought to be created, or encoded, by modifications in synaptic strength.

Dr. Yasuda's team has been looking at the behaviors of proteins involved in synaptic plasticity within dendritic spines - small bristles on the surface of neurons that receive synaptic signals. There are roughly 10,000 spines on the dendritic branches of each neuron (and roughly 100 billion neurons in the adult brain).

His team's most surprising finding, he said, was that induction of LTP in as few as three of these spines was sufficient to exert profound effects on activity of proteins that control gene transcription in the cell nucleus. The team also discovered that these spines needed to be distributed over at least two dendritic branches for this process to be triggered. Efficiency of gene transcription was higher with a more geographically distributed pattern of spines.

The Science report was authored by Shenyu Zhai, Eugene D. Ark, Paula Parra-Bueno and Yasuda. Zhai and Ark are affiliated with the Department of Neurobiology at Duke University Medical Center.

It took the team nearly four years to confirm the results and understand the mechanisms involved. An enabling key to the research, Yasuda said, are the advancements in imaging technologies. Some of those advances, including the technology to visualize and record biochemical reactions during synaptic strengthening, were developed by Yasuda and his group. "With our imaging technology, we can directly monitor the activity of the proteins," he said. "That is very powerful."

Unraveling this signaling pathway is expected to lead to clinical applications and contribute, for example, to our understanding of how alterations in LTP may factor into a number of neurological diseases, including Parkinson's, epilepsy and Alzheimer's. "Understanding the mechanisms of how it works," Yasuda said, "should provide us insights into new therapeutics for these diseases."