Fear Memories and CREB - Dana Walker

Han's 2009 articles establishes that CREB-expressing neurons are crucial to the expression of a fear memory. Their other findings indicate that neurons in the lateral amygdala that show increased levels of CREB (via HSV vectors) are preferentially activated when creating an auditory fear memory. Therefore, they hypothesized that destroying these neurons with DT/DTR would disrupt the memory. CREB-cre, Cntrl-cre, and CREB were injected into iDTR mice and control mice, making six groups. They first confirmed that CREB-cre neurons are more likely to be activated by fear memory testing than neurons not expressing an increase in CREB. This effect was also seen for strong memory training. Furthermore, by having this selection of cells undergo apoptosis, the weak fear memory disappeared. Deleting other nearby neurons that were not involved in fear memory formation had no effect on memory. Further tests also confirmed that this memory loss is independent of memory reactivation, and it does not damage future memory storage.

Yiu's 2014 article builds on Han's findings and further investigates the mechanisms dictating which neurons are recruited for fear memories. CREB is involved in many processes, and it is unknown how exactly it is important for memory formation. The authors demonstrated excitability before training influences which neurons are allocated to a fear memory, first by infecting neurons in the lateral amygdala with HSV expressing dnKCNq2 or Kir2.1 The former increases excitability, while the latter decreases it. Kir2.1 also blocked the ability of CREB to increase excitability. Expressing CREB or dnKCNQ2 either two days before or immediately before weak auditory fear conditioning increased excitability and enhanced the fear memory. These effects were not affected by the act of performing surgery, and injecting CREB or dnKCNq2 after fear training had no effect on the resulting memory. Finally, reactivating these infected neurons containing the fear memory successfully produced fear responses, even in a new context.

These articles are a good continuation of the concepts in last week's articles. The use of optogenetics and synthetic memory activation is an application that I had not previously thought of. However, only auditory fear memories were mentioned. I wonder if different fear memories that are potentially encoded in different areas of the brain are affected differently by excitability and areas of the amygdala. I'd be interested in seeing a similar experiment with visual fear conditioning.

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