시냅스의 functional and structural change의 correlation

https://medicalxpress.com/news/2020-06-weaken-notion-size-equals-strength.html

 

Learning, memory and behavioral disorders can arise when the connections between neuron, called synapses, do not change properly in response to experience.

could yield new treatments for a disorder called Fragile X that causes autism.

Two classic forms of synaptic plasticity are that synapses either get stronger or weaker and that the tiny spine structures that support them get bigger or smaller. For a long time, the field's working assumption has been that these functional and structural changes were closely associated: strengthening went along with an increase in spine size and weakening preceded spine shrinkage. But the study published in Molecular Psychiatry adds specific evidence to support a more recent view, backed by other recent studies, that those correlations are not always true.

"One conclusion is you can't use spine size as a proxy for synaptic strength—you can have weak synapses with big bulbous spines. We are not the only ones to make this case, but the new results in this study are very clear."

To conduct the study the team stimulated plasticity via two different neural receptors (called mGluR5 and NMDAR) under two different conditions (neurotypical rodents and ones engineered with the mutation that causes Fragile X). In Fragile X, Bear's lab has found the lack of the protein FMRP leads to excess synthesis of other proteins that cause synapses to weaken too much in a brain region called the hippocampus, which is a crucial area for memory formation.

The first surprise of the study was that activating mGluR5 receptors induced the weakening, called long-term depression (LTD), but did not lead to any spine shrinkage in either Fragile X or control mice for at least an hour. In other words, the structural change that was assumed to go along with the functional change didn't actually occur.

In the NMDAR case, the two forms of plasticity did occur together, both in control and fragile X rodents, but not without a few more surprises lurking just beneath the surface that further dissociated functional and structural plasticity. When the team blocked a flow of ions (and therefore electric current) in the NMDAR synapses, that only prevented the weakening, not the shrinking. To prevent the shrinking in control rodents, the researchers had to do something different: inhibit protein synthesis either directly or by inhibiting a regulatory protein called mTORC1.

 

reference

Molecular Psychiatry (2020). DOI: 10.1038/s41380-020-0821-6