Cortisol Suppression in the Early Morning Enhances Memory Reconsolidation
Post by Andrew Vo
What's the science?
Our memories are not concrete, they are malleable and susceptible to change through a process known as reconsolidation. It has been proposed that manipulations of sleep and levels of the stress hormone cortisol can modulate reconsolidation and alter reactivated memories, however the direction of such effects is still unclear. Cortisol levels normally decrease during the evening but rise in the early morning and can also be manipulated pharmacologically. This week in The Journal of Neuroscience, Antypa et al. examine the effects of pharmacological cortisol suppression following memory reactivation on later memory retrieval.
How did they do it?
A group of healthy young adults participated in two experimental conditions (i.e., drug and placebo) spaced a minimum of 10 days apart. In each condition, participants completed (1) an encoding session, (2) a reactivation session, and (3) a retrieval session. In the encoding session, they were presented with two stories, each composed of visual slides and auditory narration. In the reactivation session that took place 2 days after encoding, participants slept in the lab from 11:00 p.m. until 3:55 a.m. when they were awakened, and one of the two encoded stories was reactivated through a cueing procedure. At 4:00 a.m., they were administered either metyrapone (a cortisol synthesis inhibitor) or a placebo before returning to bed until a 6:45 a.m. awakening. Salivary cortisol samples were collected immediately before drug intake as well as in 15-minute intervals for 3 hours after the second awakening (i.e., 6:45 a.m. to 9:45 a.m.). In the retrieval session that took place 4 days after reactivation, participants completed a multiple-choice recognition memory test on both the reactivated and non-reactivated stories. Finally, a subset of participants completed whole night polysomnography (PSG) recording for both experimental conditions.
What did they find?
Cortisol suppression via metyrapone administration just after memory reactivation enhanced performance on the multiple-choice recognition memory test in the retrieval session. This effect was not only greater for the reactivated relative to the non-reactivated story in the drug condition, but also in comparison to both reactivated and non-reactivated memories under placebo. Memory enhancement for the reactivated versus non-reactivated story negatively correlated with metyrapone-associated cortisol suppression during but not after sleep. That is, the more cortisol levels were suppressed, the more memory for the reactivated story was enhanced.
Analysis of salivary cortisol samples revealed that baseline levels (at 3:55 a.m.) did not differ between the two experimental conditions. These levels gradually lowered after awakening (6:45 to 9:45 a.m.) following metyrapone administration. Examining PSG recordings in a subset of participants, metyrapone affected subsequent sleep by increasing awake time, altering the proportion of time spent in different sleep stages, reducing total sleep time, and decreasing sleep efficiency. These metyrapone-associated changes in sleep correlated with cortisol decrease but not memory enhancement for the reactivated versus non-reactivated story because of metyrapone intake.
What's the impact?
In summary, this study demonstrated that metyrapone-mediated cortisol suppression immediately following memory reactivation enhanced reconsolidation and later recall of that memory. These findings demonstrate a cognitive (reconsolidation), physiological (sleep and cortisol levels), and pharmacological (metyrapone intake) mechanism through which episodic memories may be manipulated. Understanding of these processes holds potential clinical implications for the treatment of individuals with disease, trauma, or stress-related memory impairment.
Antypa et al. Suppressing the Morning Cortisol Rise After Memory Reactivation at 4 A.M. Enhances Episodic Memory Reconsolidation in Humans. The Journal of Neuroscience (2021). Access the original scientific publication here.