The Durk Pearson & Sandy Shaw®
Life Extension NewsTM
Volume 18 No. 4 • August 2015

Remembering a Pleasant Experience Protects Mice Against Stress Whereas Experiencing the Pleasant Experience Does Not

Huh? What? You might wonder about the title of this piece. How can it be that remembering a pleasant experience protects mice against “depressive-like stress responses” (Ramirez, 2015) by reactivating neurons that had previously been activated by a positive experience. Yet the pleasant experience itself did NOT provide this stress protection. Here is a paper worth thinking about because if we can use a method similar to what they used in the study to induce remembering a pleasant experience, we might also obtain this “enduring” protection against stress.

Here’s how the experiment was done. A section of the hippocampus that contributes to the generation of cellular representations of experiences by activating neurons is called the dentate gyrus. The dentate gyrus can be genetically tagged with light sensitive molecules while an animal is undergoing an experience. The dentate gyrus can subsequently be reactivated by pulses of light and, the scientists report, exhibit behavior that suggests they are recalling the experience. The physical substrate that is thought to comprise the memory of the experience is called an engram.

The mice with the light tagged dentate gyrus were subject to three possible experiences: a positive one where the male mice were put in a cage with a sexually receptive female, a neutral one where the male mice were put in an empty cage, and a negative one where they were immobilized, thereby being stressed. Following this, all the mice were subsequently exposed to stress for 10 consecutive days. Unsurprisingly, the mice became depressed and lost interest in things they enjoyed previously.

The scientists found that when they reactivated the engram every day for five days (by stimulating the tagged neurons with light), the previously stressed animals had their depressive-like symptoms of passivity and anhedonia REVERSED on day six. Yet exposing the animals to the original pleasant experience did NOT provide this effect.

The reason for this effect was not determined by the scientists that did the experiments. They provided some guesses. For example, the commentary (Dranovsky, 2015) on this study speculated that repeated recall of positive memories might result in resilience to adversity and that nostalgia is a human activity that might serve a stress-reducing purpose.

How might we duplicate these results? It has already been found that memories can be re-experienced during sleep in animals and in humans by playing a sound associated with the original experience itself. Why not just use a short clip of music that has some emotional content to “code” an experience while you undergo it and then the playing of the musical clip might perform a similar function as the light did in the light tagged dentate gyrus of the mice, by inducing a re-experiencing of the original pleasant event. Any human alive must have noticed that certain pieces of music are connected to certain events in a person’s life and induce emotions that connect to those events. Hence, it seems very plausible that this very simple method might do for us what the sophisticated method of light tagging did in the mice.

An aroma might also serve as the associated tag. Scents are processed in an extremely ancient part of the brain.

Nevertheless, neither the commentary or the paper cited here actually noted the potential use of music or scents for this remarkable stress resistance. The authors of the paper (Arzi, 2012), in fact, speculate that “exposure to natural exogenous positive cues may not be able to access similar neural pathways in subjects displaying depression-like symptoms such as passive behavior in challenging situations and anhedonia.” (No references supported this speculation.)

Here we cite a couple of the very many papers showing that exposure to sensory cues, such as music or smells, can (by being administered during an experience and then administered again during sleep), result in enhanced alertness and memory following sleep in humans and in animals.


  • Ramirez, Liu, MacDonald, et al, Activating positive memory engrams suppresses depression-like behaviour. Nature. 522:335-9 (2015).
  • Dranovsky and Leonardo. The Power of Positivity. Nature. 522:294-5 (2015).
  • Arzi, Shedlesky, Ben-Shaul, et al. Humans can learn new information during sleep. Nat Neurosci. 15(10):1460-5 (2012). In this paper, researchers showed that “sleeping subjects learned novel associations between tones and odors such that they then sniffed in response to tones alone.” The sniffing behavior differed according to the pleasantness of the odor. There was no later awareness of this learning process.
  • Also see Payne. Sleep on it!: stabilizizng and transforming memories during sleep. Nat Neurosci. 14(3):272-4 (2011). In this commentary paper (original paper, Diekelmann, 2011), presenting an odor during wakefulness rendered memories that were reactivated during slow wave sleep to be stabilized for the waking event during which the odor was administered. This reactivation was show by fMRI to activate the hippocampus and posterior cortical regions.
  • Diekelmann, Büchel, Born, Rasch. Labile or stable: opposing consequences for memory when reactivated during waking and sleep. Nat Neurosci. 14:381-6 (2011).

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