The strength of synapses -- the communication connections among nerve cells -- underlies our ability to learn and remember. A Picower Institute for Learning and Memory researcher reports in the Nov. 4 issue of Science that a kind of "backtalk" from a postsynaptic cell is crucial in the chemical and electrical dance that drives synapse development.
"This mechanism can mediate which synapses get reinforced and which do not," said J. Troy Littleton, associate professor of biology in the Picower Institute. "Knowing how this mechanism works at the molecular level may allow us to influence how synapses are modified during neuronal plasticity and ultimately influence brain storage mechanisms that are affected in neurological diseases such as Alzheimer's."
Littleton studies plasticity, the brain's amazing ability to change in response to stimuli. Throughout life, synapses are bolstered or killed off in a complex interplay of genes and environment.
Synapses undergo physical changes to become stronger after each use. To achieve these changes, an influx of information travels from the presynaptic cell to the postsynaptic cell. Surprisingly, the researchers found that robust stimulation of neurons results in information that also is transferred back to the presynaptic neuron. These are called retrograde signals.
It is the nature and effect of these signals that Littleton and his co-authors -- Picower Institute research scientist Motojiro Yoshihara, graduate student Bill Adolfsen and MIT affiliate Kathleen T. Galle -- investigate in the nervous systems of fruit flies. Their work sheds light on the "use it or lose it" theory of synapse formation.
Previous research had shown that synapses involved in memory formation remain electrically and chemically active while undergoing structural changes that consolidate their newfound strength.
Calcium is key to the chemical signaling that strengthens or breaks synaptic connections. In the Science paper, the MIT researchers report that calcium-dependent retrograde signaling was responsible for a miniature burst of postsynaptic activity that helped the synapse consolidate its latest structural changes.
After an initial burst of electrical stimulation, mimicking an influx of sensory stimulation, a "mini" burst onto the postsynaptic cell continued for as long as 20 minutes before dying down. "This work suggests a previously unknown role for miniature release in neuronal function," Littleton said.
This work was supported by the National Institutes of Health, the Human Frontiers Science Program Organization, the Packard Foundation and the Searle Scholars Program.
