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Week 4 - Caity Forgey

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The paper this week by Yiu et al. (2014) builds off of their earlier work in the paper by Han et al. (2009). Both papers share many of the same authors and come from the Josselyn Lab. Han and colleagues examined the role of lateral amygdala (LA) neurons and the memory trace, and demonstrated their mechanism to selectively erase an auditory fear memory by ablation of LA neurons included in the trace. To do this, they used diptheria toxin (DT) to ablate neurons overexpressing the transcription factor CREB. They found that their tactic successfully erased a learned fear memory and the effects were long-lasting and robust. In the second paper by Yiu and colleagues, this finding was built upon by examining whether expression of CREB, or excitability in general, would preferentially recruit specific LA neurons into a memory trace. Yiu et al. demonstrated this through the use of CREB, dnKCNQ2, hM3Dq+DREADD+CNO, and optogenetics. Their findings confirmed the competitive recruitment of the most excitable neurons (compared to their neighboring neurons) into a memory trace, that this is specific to the LA neurons (rather than CeA or BA) and is specific to the learned fear memory and not general anxiety-like behaviors.

Together, these findings provide a case for the importance of excitatory pyramidal LA neurons for the formation (and ablation) of  a learned fear memory. This has clinical applications for disorders that rely on fearful memories, such as PTSD. I am interested in seeing how this would apply to other mood disorders, like depression and anxiety, which are strongly correlated with the experience of trauma. Obviously, we cannot just open a human brain and stimulate or inhibit some neurons to eliminate PTSD, but this could provide a potential target region for pharmacological treatments.

I would also like to see additional work investigating memories of different connotations, such as reward learning, pleasant memories, neutral memories, and sad (but not fearful) memories. It is possible that LA neurons would not be implicated in these types of memories, or that other amygdalar regions would be more so implicated in emotional memory traces of different valences and arousal levels.

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