Introducing the brain: hippocampal controls (Introduction)

by David Turell , Wednesday, June 07, 2023, 19:33 (325 days ago) @ David Turell

Small special molecules:

https://www.the-scientist.com/news-opinion/short-lived-molecules-support-long-term-memo...

"Among the genes essential for synaptic remodeling during memory formation is the activity-regulated cytoskeletal associated (Arc) gene, whose mRNAs and proteins have a half-life of about an hour. Reconciling how these molecules produce changes on scales of hours or even days was one of the primary motivations for this study, said Sulagna Das, an RNA biologist and neuroscientist at the Albert Einstein College of Medicine and coauthor of this work.

"Das’s team tackled the question by visualizing all of the steps, tracking the mRNA from birth, following where they go and where they localize, watching when they are translated into proteins, and determining how long the proteins stay in the synapses. For this, the team fluorescently tagged the Arc gene and followed the journey of its mRNAs and proteins for several hours within individual brain cells after one initial chemical or optogenetic stimulus, both in cultured mouse hippocampal neurons and in mouse brain tissue.

"By closely spying on these molecules, Das and her colleagues found that a single initial stimulus resulted in a series of cycles of transcription. The first one was initiated by the stimulus, but the subsequent ones were induced by the translated Arc proteins themselves, suggesting the existence of a positive feedback loop.

"mRNAs produced during the second transcription cycle move to the dendritic regions populated by the translated proteins of the first cycle, leading to local translation and the formation of protein hubs. “That's how you can build up a lot of protein at a single location,” Das explained, and it’s important because this mechanism gives specificity to which synapses are being stabilized for long-term information storage."

Comment: This process takes many small steps, each dependent upon the last one. It cannot be developed by chance mutations and must be designed all at once fitting the steps together.