Biochemical controls: maintaining a memory (Introduction)

by David Turell , Wednesday, May 07, 2025, 19:38 (23 hours, 18 minutes ago) @ David Turell

Fixes a synapse:

https://www.quantamagazine.org/the-molecular-bond-that-helps-secure-your-memories-20250...

"The researchers discovered that a persistent bond between two proteins(opens a new tab) is associated with the strengthening of synapses, which are the connections between neurons. Synaptic strengthening is thought to be fundamental to memory formation. As these proteins degrade, new ones take their place in a connected molecular swap that maintains the bond’s integrity and, therefore, the memory.

"The researchers present “a very convincing case” that “the interaction between these two molecules is needed for memory storage,” said Karl Peter Giese(opens a new tab), a neurobiologist at King’s College London who was not involved with the work. The findings offer a compelling response to Crick’s dilemma, reconciling the discordant timescales to explain how ephemeral molecules maintain memories that last a lifetime.

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"Every time he repeated the experiment, he saw elevated levels of a certain protein within the synapses. “By the fourth time, I was like, this is it,” he said.

"It was protein kinase M zeta, or PKMζ for short. As the rats’ hippocampal tissue was stimulated, synaptic connections strengthened and levels of PKMζ increased(opens a new tab). By the time he published his findings in 1993, he was convinced that PKMζ was crucial for memory.

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"When Sacktor blocked the molecule’s activity an hour after a memory was formed, he saw that synaptic strengthening was reversed. This discovery suggested that PKMζ was “necessary and sufficient(opens a new tab)” to preserve a memory over time, he wrote in Nature Neuroscience in 2002. In contrast, hundreds of other localized molecules impacted synaptic strengthening only if disrupted within a few minutes of a memory’s formation. It appeared to be a singular molecular key to long-term memory.

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"In 2016, they published a rebuttal(opens a new tab), demonstrating that in the absence of PKMζ, mice recruit a backup mechanism, involving another molecule, to strengthen synapses.

"The existence of a compensatory molecule wasn’t a surprise. “The biological system is not such that you lose one molecule and everything goes. That’s very rare,” Giese said. But identifying this compensatory molecule prompted a new question: How did it know where to go to replace PKMζ? It would take Sacktor and Fenton nearly another decade to find out.

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"But are the KIBRA-PKMζ complexes needed to maintain memory over the long term? To find out, the researchers disrupted the complex four weeks after a memory was formed. Doing so did indeed wipe out the memory. This suggested that the interaction between KIBRA and PKMζ is crucial not only for forming memories, but also for keeping them intact over time.

“'It’s the persistent association between two proteins that maintains the memory, rather than a protein that lasts by itself for the lifetime of the memory,” said Panayiotis Tsokas, a researcher working with Sacktor and lead author on the new Science Advances paper.

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"This work also answers a question that researchers had put on the shelf. Sacktor’s earlier study showed that increasing levels of PKMζ strengthened synapses and memories. But how did the molecule know where to go within the neuron? “We figured, well, one day, maybe we’ll understand that,” Sacktor said. Now, the researchers think that KIBRA acts as a synaptic tag that guides PKMζ. If true, this would help explain how only the specific synapses involved in a particular physical memory trace are strengthened, when a neuron may have thousands of synapses that connect it to various other cells.

Comment: maintaining a memory involves maintaining a synapse all controlled by specific proteins, no thought involved by the proteins themselves.