Skip to main content

Memory and the BLA

By

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.

Comments

Post a Comment

Popular posts from this blog

Week 2- Dopamine Modulation of Depressive-like Behaviors

By
The Chaudhury et al paper explored the neural circuit mechanisms involved in the dopamine modulation of certain symptoms of depression. In this study, the researchers looked at social interaction and sucrose preference as part of their social-defeat paradigm, which has been shown in the past to be indicative of depressive-like behaviors. Although I initially did not completely see the connection between the social-defeat stress model of depression and the tonic vs phasic firing of dopamine neurons, it seemed that susceptibility and resilience to stress played a role in the functional/behavioral effects of dopamine firing. It was interesting to see how chronic mild stress with phasic firing of VTA dopamine neurons converted even resilient mice into susceptible mice.  The Tye et al paper similarly looked at the dopamine modulation of depressive-like behaviors, focusing on motivation with the forced swim tests and open field tests, followed by measurement of anhedonia by quantifyi...
Post a Comment
Read more

Sial & Allsop

By
Sial et al. derived a novel approach for studying what they deem vicarious defeat stress (VSDS) as a model for MDD, PTSD, and other mood-related disorders as an alternative to the classical CSDS paradigm. Using adult male mice, they demonstrate that their model induces a robust and measurable social avoidant phenotype as well as other stress and anxiety related behavioral outputs. Their subsequent rescue study with chronic fluoxetine treatment shows reversal of the behavioral phenotypes and emphasizes the predictive validity of the model. Allsop et al. found that BLA-projecting ACC neurons preferentially encode socially derived aversive cue information by encoding the demonstrator’s distress response during observational learning, hence enabling acquisition of negative valence of cue by BLA neurons and behavioral output. In order to test their hypothesis, Allsop et al. used an observational fear conditional paradigm to create association between a conditioned stimulu...
Post a Comment
Read more

Buffington and Reber

By
Buffington et al. explore a mechanism by which maternal obesity can induce neuronal and subsequent behavioral disorders. Using a model of high-fat diet (MHFD)-induced obesity, the authors showcase the strong connection between the brain and the gut, and its impact on behavior. The findings are provocative; by exposing these offspring to the microbiome of control offspring, there was evidence of a rescued observed behavioral phenotype. Furthermore, a phylogenetic profiling of the gut microbiome revealed a decrease in L. reuteri within MHFD offspring, and introduction of live L. reuteri into the drinking water shows successful rescue of the behavioral issues in the MHFD offspring. L. reuteri-induced expression of oxytocin within the paraventricular nuclei of the hypothalamus provides a potential mechanistic explanation for the behavioral changes. I thought this paper provided robust support for the hypothesized interaction between the gut biome and the developing CNS, with tremendous po...
Post a Comment
Read more