Surgery News

Protein synaptotagmin-IV helps maintain an efficient brain

January 26, 2016

"When we stimulate brain pathways heavily with this experiment, we see that synapses are reinforced and produce bigger responses," says Chapman. "The synapses remember the stimulation, they learn something from it and we can see evidence of that."

Despite having learning disabilities, the Syt-IV-free mice produced improved LTP. In fact, it was too high.

"If synapses are tweaked to the max, as they were in this case, they lose plasticity and don't work well," says Chapman. "The overload also can lead to seizures."

The researchers believe that Syt-IV serves as a way to maintain synaptic homeostasis - or internal equilibrium - by reigning in LTP to a normal level.

The protein does its work indirectly by regulating brain-derived neurotrophic factor (BDNF), a growth factor essential for long-term nerve cell well-being. In recent years, BDNF also has been shown to affect synapses.

In the experiments, Syt-IV pulled down elevated LTP by restricting the release of BDNF on the receiving side of the synapse, gearing down synaptic activity.

"Syt-IV dynamically regulates LTP as it goes up and down, holding the activity in balance," he says. "For plasticity, you need a good dynamic range of synaptic activity - from low to high."

Meyer B. Jackson, Huisheng Liu, F. Mark Dunning and Payne Y. Chang were co-authors on the paper.