Re-activation positive memory alleviate depressive symptom

Dranovsky, A., & Leonardo, E. D. (2015). The power of positivity. Nature, 522, 294. doi:10.1038/522294a
Ramirez, S., Liu, X., MacDonald, C. J., Moffa, A., Zhou, J., Redondo, R. L., & Tonegawa, S. (2015). Activating positive memory engrams suppresses depression-like behaviour. Nature, 522, 335. doi:10.1038/nature14514

I didn't totally understand the experiments in Ramirez et al (2015), but it reads like a lot of works had been done by the authors. 

The basic idea is simple: if we re-activated the positive memory of mice that currently depressed, the positive memory will decrease the depressive behaviours. This basic idea was clearly illustrated by Dranovsky & Leonardo (2015), see below

Of course, the actual experiment is more complicated, as well as the figures:

The above figure is the figure 1a of Ramirez et al. (2015). So, there are 6 groups. The key manipulation is the positive experience, which was exposed the mice to a female conspecific in a home-like situation, the negative experience was fixed in a tube in which the mice can't move ( chronic immobilization stress, CIS). After that, the authors used the optogenetic method to re-activate the neurons that responsible for the positive experience and found that the depressive behaviours were decreased.

Then, the authors localized the brain structures that responsible for this effect, i.e. the c-Fos expression. They found that nucleus accumbens (NAcc) shell, lateral septum, basolateral amygdala (BLA), central amygdala, as well as the dorsomedial, ventromedial, and lateral hypothalamus, NOT mPFC.

The next step is going further and see whether this effect has a long-term effect, and found that 5-day re-activation of positive experience, instead of one-day or no re-activation, showed a reversal of depressive behaviour!

One important message in the discussion part of this article is: depression-like behaviours of the mice were ameliorated by re-activated of positive experience, but anxiety-like behaviours not. 

OK, this group is fantastic, because their engram cell studies all published on science or nature, so not surprising this paper also appeased on nature.

PS: I searched articles that cited this paper, and selected a few important ones.

Anacker, C., & Hen, R. (2017). Adult hippocampal neurogenesis and cognitive flexibility — linking memory and mood. Nature Reviews Neuroscience, 18, 335. doi:10.1038/nrn.2017.45

In this review, the authors concluded that "improved cognitive flexibility may in turn help to decrease anxiety-like and depressive-like behaviour." This conclusion is very closely related to Raffael's idea.

Etkin, A. (2016). Remember the Good Times? Biased Autobiographical Memory in Depression. American Journal of Psychiatry, 173(1), 8-9. doi:10.1176/appi.ajp.2015.15101313

This editorial introduced a study by Young, K. D., Siegle, G. J., Bodurka, J., & Drevets, W. C. (2016). [Amygdala Activity During Autobiographical Memory Recall in Depressed and Vulnerable Individuals: Association With Symptom Severity and Autobiographical Overgenerality. American Journal of Psychiatry, 173(1), 78-89. doi:10.1176/appi.ajp.2015.15010119], which found that depressive individual has less positive memory and abnormal amygdala activity. Young et al's paper should be my next read, because autobiographic memory is always related to my studies.

Holmes, E. A., Blackwell, S. E., Heyes, S. B., Renner, F., & Raes, F. (2016). Mental Imagery in Depression: Phenomenology, Potential Mechanisms, and Treatment Implications. Annual Review of Clinical Psychology, 12(1), 249-280. doi:10.1146/annurev-clinpsy-021815-092925

This review mainly summarized the contribution of imagery dysfunctions to depressive psychopathology and implications for cognitive behavioral interventions.

Hu, H. (2016). Reward and Aversion. Annual Review of Neuroscience, 39(1), 297-324. doi:10.1146/annurev-neuro-070815-014106

This review focused on the functions of DA and 5-HT systems in coding the distinct components of rewards.

Josselyn, S. A., Köhler, S., & Frankland, P. W. (2015). Finding the engram. Nature Reviews Neuroscience, 16, 521. doi:10.1038/nrn4000
Kitamura, T., Ogawa, S. K., Roy, D. S., Okuyama, T., Morrissey, M. D., Smith, L. M., . . . Tonegawa, S. (2017). Engrams and circuits crucial for systems consolidation of a memory. Science, 356(6333), 73-78. doi:10.1126/science.aam6808
Tonegawa, S., Liu, X., Ramirez, S., & Redondo, R. (2015). Memory Engram Cells Have Come of Age. Neuron, 87(5), 918-931. doi:https://doi.org/10.1016/j.neuron.2015.08.002

These three papers discussed the engram, which is out the scope of my knowledge.

Murphy, S. E., Clare O’Donoghue, M., Drazich, E. H. S., Blackwell, S. E., Christina Nobre, A., & Holmes, E. A. (2015). Imagining a brighter future: The effect of positive imagery training on mood, prospective mental imagery and emotional bias in older adults. Psychiatry Research, 230(1), 36-43. doi:https://doi.org/10.1016/j.psychres.2015.07.059

This seems like the only paper that actually continues the "positive-memory-suppress-negative-memory" logic. The authors trained aged people using a magery cognitive bias modification and found that the training increased the vividness of positive memory, but negative interpretation bias is not changed.