Causal evidence for the role of REM sleep theta rhythm in contextual memory consolidation
Authors: Stephen D Glasgow
Antoine Adamantidis
Richard Boyce
Sylvain Williams
Journal: Science (2016)
Discipline: Multidisciplinary
Keywords: Rapid eye movement sleep; REMS; memory consolidation; neural activity; optogenetic silencing
Affiliations: Integrated Program in Neuroscience, McGill University, Montreal, Quebec, Canada., Department of Psychiatry, McGill University, Montreal, Quebec, Canada., Department of Psychiatry, McGill University, Montreal, Quebec, Canada.  ., Department of Psychiatry, McGill University, Montreal, Quebec, Canada. Department of Neurology and Department of Clinical Research, Inselspital University Hospital, University of Bern, Bern, Switzerland.  .

Abstract:  Rapid eye movement sleep (REMS) has been linked with spatial and emotional memory consolidation. However, establishing direct causality between neural activity during REMS and memory consolidation has proven difficult because of the transient nature of REMS and significant caveats associated with REMS deprivation techniques. In mice, we optogenetically silenced medial septum Œ≥-aminobutyric acid-releasing (MS(GABA)) neurons, allowing for temporally precise attenuation of the memory-associated theta rhythm during REMS without disturbing sleeping behavior. REMS-specific optogenetic silencing of MS(GABA) neurons selectively during a REMS critical window after learning erased subsequent novel object place recognition and impaired fear-conditioned contextual memory. Silencing MS(GABA) neurons for similar durations outside REMS episodes had no effect on memory. These results demonstrate that MS(GABA) neuronal activity specifically during REMS is required for normal memory consolidation. 

Retracted: No

PubPeer comments:
 I believe this paper contains a number of incorrectly applied statistical procedures.  In Fig. 1D (above), in the second row, left-most inset, the authors compare spectral power with and without light (triggering optogenetic inhibition). They use a two-way ANOVA followed by a Tukey post-hoc test. I believe the ANOVA is invalid for two reasons: i) the variances of the power at the different frequencies are quite different, violating the assumption of equal variance, ii) the design appears to involve  repeated measures , because each animal yields parallel measurements for each frequency band. Furthermore, the design implicitly involves a third factor, which is the ArchT YFP genotype, but that factor is not incorporated and that interaction has therefore not been tested. I could find no explanation of the  0.07 appearing in those inserts.  In Fig. 3E (above), the authors compare  Object 2 discrimination indices between two days, where a difference would reflect formation of a memory. Depending on the experimental conditions, some of the comparisons are reported as significant or not. However, the aim of the experiment is to show that the memory formation can be disrupted, so it is necessary to compare the (day 2) - (day 1) differences, which does not appear to have been done.  The difference between significant and non-significant is non-significant .  In Fig. 4D (above), the two-way ANOVA is, I believe, invalid; a repeated-measures test should have been used instead. It is stated that the results are  confirmed with Kruskal-Wallis test , but I believe this is a one-way test. If that is so, it would presumably have been applied separately at each time? Without correction for mutliple comparisons? ,