Introducing the brain: silent synapses II (Introduction)

by David Turell , Friday, March 31, 2023, 15:41 (601 days ago) @ David Turell

More research:

https://www.the-scientist.com/news-opinion/silent-synapses-may-provide-plasticity-in-ad...

"Silent synapses are otherwise complete neuronal connections that lack a key signaling protein—AMPA receptors—that renders them inactive. They were thought to be unique to early development, as previous work found that the silent connections vanish by the time a mouse has reached adulthood. But researchers may have been looking in the wrong place. In young animals, silent synapses are formed from larger protrusions called dendritic spines. But in adults, they can be found on the ends of threadlike structures called filopodia, according to the new study.

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"They found that the tips of filopodia were indeed covered with AMPA-deficient synapses. Without AMPA, synapses cannot be activated, as the receptors clear magnesium ions that obstruct other receptors integral to synaptic transmission.

"They also realized that filopodia are far more widespread than they anticipated. They were found all over the brain and at levels ten times higher than previously described, making up 30 percent of the protrusions on a given dendritic branch. This suggests a similar proportion of synapses in the adult mouse brain are silent, waiting to be activated.

"To confirm that the synapses were in fact silent, the researchers released the neurotransmitter glutamate at the tips of filopodia to mimic activity in a neighboring neuron. Unlike the synapses on dendritic spines, which responded with a burst of electrical activity, the synapses on filopodia were unresponsive. When the team washed away the magnesium ions from the same filopodium—unblocking receptors typically activated by AMPA—the silent synapse discharged a babble of electricity.

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"The researchers then went a step further, unsilencing the synapse by injecting a current into an AMPA-deficient neuron while pouring glutamate onto its filopodia. This mimics the simultaneous firing of two neurons connected by the silent synapse. After just a few rounds of stimulation, AMPA receptors accumulated on the synaptic membrane and the filopodia started to resemble a dendritic spine. Performing the same experiment on dendritic spines, however, had no effect.

"The results suggest that the adult brain is far more plastic than was previously thought, says neuroscientist Gregor Schuhknecht of Harvard University, who was not involved in the study. It shows that “there’s a vast capacity for circuit remodeling,” he adds.

"The study may explain how the brain is able to learn new things without having to sacrifice existing connections, the researchers say. The ability of the brain to use different synapses “solves the plasticity versus flexibility dilemma,” says Harnett. If all the brain’s synapses are flexible, then you can’t preserve old information. But if they’re all stable, then it is difficult to learn new things, he says. Instead, the brain employs both: spiny synapses for stability and filopodia for flexibility.

"But instead of distinct categories, Harnett’s group are beginning to think about dendritic projections as existing on a continuum, from filopodia on one end to mature spines at the other. “It is a spectrum of maturity, strength, and plasticity,” says study author Dimitra Vardalaki, a PhD candidate in Harnett’s lab."

Comment: there had to be a way for much older brains to learn by plasticity, creating new connections, since we don't make new neurons.