Posts Tagged ‘hippocampus’

How do neurons form long term memories ?

Reporter: Irina Robu, PhD

Neuroscientists at Harvard medical School are trying to understand the biology of long-term memory and fine ways to intercede when memory deficits happen with age or disease. They identified a new mechanism that neurons in the adult mouse hippocampus use to control signals they collect from other neurons, in a process that looks critical for memory consolidation and recall.

The investigators detected new experiences activate sparse populations of neurons in the hippocampus that express two genes, Fos and Scg2. The genes permit neurons to fine-tune inputs, to dampen neuronal excitation. The mechanism allows neurons to better talk to each other so that the next time a memory needs to be remembered, the neurons fire extra synchronously.

According to Dr. Yap and his team, the brain must somehow wire an experience into neurons so that when these neurons are reactivated, the initial experience can be recalled. Researchers hypothesized that Fos can play a vital role in learning and memory, but for decades, the precise function of the gene has stayed a mystery. In order to investigate their theory, the researchers exposed mice to new new environments and observed at pyramidal neurons. They observed that relatively sparse populations of neurons express Fos After exposure to a new experience. Then they prevent these neurons from expressing Fos, using a virus-based tool delivered to a specific area of the hippocampus, which left other cells unaffected.

Mice that had Fos blocked in this manner presented noteworthy memory deficits when evaluated in a maze that required them to recollect spatial details, representing that the gene plays a vital role in memory formation. They evaluated the differences between neurons that expressed Fos and those that did not. Withoptogenics to turn inputs from nearby neurons on or off, they discovered that the activity of Fos-expressing neurons was affected by two types of interneurons. Neurons expressing Fos were created to receive increased activity-dampening signals from one different type of interneuron and reduced inhibitory signals from another type. These signaling patterns vanished in neurons with blocked Fos expression.

Upon further investigation, the researchers looked at the function of Fos, which codes for a transcription factor protein that regulates other genes, which uses single-cell sequencing and additional genomic screens to classify genes activated by Fos. They  found that Scg2 gene played a critical role in regulating inhibitory signals.

In mice with Scg2 gene is silenced by experimentation,  Fos-activated neurons in the hippocampus displayed a defect in signaling and they also had defects in theta and gamma rhythms, brain properties believed to be essential features of learning and memory.

The study results indicate a possible molecular- and circuit-level mechanism for long-term memory. They showed how fundamental biology of memory formation and have broad implications for diseases of memory dysfunction.


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