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Memory and the BLA

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In “Selective Erasure of Fear Memory”, Han et al. observed that neurons in the lateral amygdala with relatively increased levels of the transcription factor CREB are known to be preferentially activated by auditory fear memory. The literature demonstrates the idea that overexpression of CREB using HSV and then a subsequent ablation of these neurons in iDTR transgenic mice causes selective memory erasure. Memory was behaviorally assessed pre and post induction of cell death in tagged LA neurons, and increasing CREB in a subpopulation of LA neurons enhances a weak memory and specifically ablating these neurons reverses this enhancement. Furthermore, if neurons overexpressing CREB are deleted, the result is long-lasting memory loss in CREB-cre mice and there is no evidence of memory recovery.

Yiu et al. conducts a robust series of experiments in a later publication elucidating that memory allocation is partially based on relative neuronal excitability of LA pyramidal/principal neuronal subpopulations at the time of conditioning or training. Although Yiu et al. is most robust in their methodologies, Han et al. really laid down the groundwork for exploring LA neurons with increased CREB in memory tracing.

Han et al. disclosed that although CREB plays an imperative role, increasing it in a subpopulation of LA neurons does not further enhance a strong memory. Moreover, Yiu et al. also discusses how the memory-enhancing effect of CREB is prevented by the decreasing excitability in the LA pyramidal/principal neurons. This stood out to me and I would be curious to see if manipulation or overexpression of any subpopulation of neurons in the LA could potentially have memory confabulation. We know the amygdala is heavily implicated in valence association, so I would be curious to see whether manipulation of the LA neurons could tag a negative memory as a positive one and vice versa. This idea was slightly presented in Steve Ramirez’s work on the DG, but the amygdala is so much more involved in emotional processing than the hippocampus so I’m wondering if this would generate more robust data. I’m both curious and excited to see how down the road, once research is more solid, how we apply this data clinically, and whether the engram will be deciphered in my lifetime.

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