Introducing the brain: addressing novelty (Introduction)

by David Turell , Thursday, February 08, 2024, 20:09 (79 days ago) @ David Turell

Mice in a different maze:

https://www.the-scientist.com/news/novelty-activates-a-long-noncoding-rna-for-spatial-l...

"Recently, a team from the Weizmann Institute of Science showed in a paper published in Cell Reports that Silc1, a lncRNA, regulated spatial learning in an unfamiliar environment in mice. Unraveling the inner workings of these complex systems could help scientists understand how the loss of learned information in neurological diseases occurs.

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"To explore the function of this lncRNA further, the team reviewed publicly available RNA-seq data sets and saw that Silc1 and Sox11 are highly expressed in the hippocampus. “This led us to focus on studying brain functions that are related to the hippocampus,” Ulitsky said. According to Ulitsky, spatial memory formation is a key function in this region of the brain.

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"Compared to mice in their usual housing, animals placed in a new environment expressed more Sox11 and Silc1. The researchers then determined if Silc1 expression drove Sox11 expression by deleting Silc1. In the absence of Silc1 in adult mice, these Sox11 targets when placed in the novel environment, and this translated to reduced production of Sox11 protein. “We were really surprised to see that it acts like an immediate early gene,” Perry said.

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"Silc1-deficient mice took longer to learn where the platform and escape tunnel were in the respective mazes compared to mice with normal Silc1 expression. However, Silc1-deficient mice and normal mice performed comparably by the end of the maze probes, indicating that Silc1 deficiency does not impair long-term memory.

“'It is really cool that the long noncoding is regulated by novelty—that you have a physiological stimulus that regulates so specifically this long noncoding RNA, and that you then also can discriminate between, for example, two types of memories that it affects: spatial memory, but not long-term memory,” said Jeroen Pasterkamp, a translational neuroscientist at University Medical Center Utrecht who was not involved in the study.

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"In a follow up analysis, the team performed single-nucleus RNA sequencing followed by gene ontology analysis on hippocampus tissues from normal and Silc1-deficient mice to explore the functions of Sox11-regulated genes. They showed that many of these genes corresponded to activities such as synaptic transmission, axon guidance, and dendritic localization. They concluded that many of the pathways that Sox11 uses for neurogenesis during development also are used for learning in the adult brain, at which time their activity through Sox11 depends on Silc1.

“'We see that a program that is typically thought to be happening only as the brain is growing and as it is forming is reactivated during memory formation,” said Ulitsky. “But on the other hand, we see that this long noncoding RNA, which is activating this program, is actually not found in the embryo at all.'”

Comment: it is interesting that a memory program only appears after birth and infants start remembering around age two to three. I don't think we need to remember swimming in the uterus.