@article {5086, title = {Eszopiclone and Zolpidem Produce Opposite Effects on Hippocampal Ripple DensityDataSheet1.docx}, journal = {Frontiers in Pharmacology}, volume = {12}, year = {2022}, month = {01/2022}, abstract = {

Clinical populations have memory deficits linked to sleep oscillations that can potentially be treated with sleep medications. Eszopiclone and zolpidem (two non-benzodiazepine hypnotics) both enhance sleep spindles. Zolpidem improved sleep-dependent memory consolidation in humans, but eszopiclone did not. These divergent results may reflect that the two drugs have different effects on hippocampal ripple oscillations, which correspond to the reactivation of neuronal ensembles that represent previous waking activity and contribute to memory consolidation. We used extracellular recordings in the CA1 region of rats and systemic dosing of eszopiclone and zolpidem to test the hypothesis that these two drugs differentially affect hippocampal ripples and spike activity. We report evidence that eszopiclone makes ripples sparser, while zolpidem increases ripple density. In addition, eszopiclone led to a drastic decrease in spike firing, both in putative pyramidal cells and interneurons, while zolpidem did not substantially alter spiking. These results provide an explanation of the different effects of eszopiclone and zolpidem on memory in human studies and suggest that sleep medications can be used to regulate hippocampal ripple oscillations, which are causally linked to sleep-dependent memory consolidation.

}, doi = {10.3389/fphar.2021.792148}, url = {https://www.frontiersin.org/articles/10.3389/fphar.2021.792148/full}, author = {Becker, Logan A. and Hector Penagos and Francisco J. Flores and Manoach, Dara S. and Matthew A. Wilson and Varela, Carmen} } @conference {4522, title = {Disruption of CA1 Sharp-Wave Ripples by the nonbenzodiazepine hypnotic eszopiclone }, booktitle = {Society for Neuroscience}, year = {2019}, month = {10/2019}, address = {Chicago, IL, USA}, author = {Becker, LA and Hector Penagos and Manoach, DS and Matthew A. Wilson and Varela, Carmen} } @article {2943, title = {Oscillations, neural computations and learning during wake and sleep}, journal = {Current Opinion in Neurobiology}, volume = {44C}, year = {2017}, month = {07/2017}, type = {Review}, chapter = {193}, doi = {https://doi.org/10.1016/j.conb.2017.05.009}, author = {Hector Penagos and Varela, Carmen and Matthew A. Wilson} } @article {3499, title = {Thalamic contribution to CA1-mPFC interactions during sleep}, number = {Program$\#$/Poster$\#$: 799.13/TT8}, year = {2017}, address = {Washington, DC}, abstract = {

The consolidation of episodic memories is thought to require precisely timed interactions between cells in the hippocampus and neocortex during sleep, but the specific mechanisms by which this dialogue unfolds are poorly understood. During sleep, activity in the hippocampus and neocortex is temporally structured by a slow oscillation (1-4Hz) that frames the occurrence of faster oscillations: spindles (7-14Hz) in neocortex, and ripples (150-200Hz) in hippocampus. The observation of spindles suggests the participation of the thalamus, but its contribution has remained an open question. I will present results from simultaneous extracellular recordings of single units and local field potentials in the midline thalamus, mPFC and CA1 in freely behaving rats.

We find that both CA1 ripples and unit firing in the midline thalamus are coordinated with the neocortical slow oscillation. Interestingly, while hippocampal ripples are more likely to occur in 250ms windows before and after neocortical K-complexes (KCs, which mark the downstate of the slow oscillation), spiking probability in a subset of thalamic units is asymmetric and increases following neocortical KCs. Of the units recorded in midline thalamus simultaneously with CA1 and mPFC (n=29), 20.7\% showed a significant increase in firing rate (\>2 standard deviations from baseline) following mPFC KCs. This finding suggests that the time following KCs (the start of the slow oscillation) is functionally different from the end of the oscillation (before KCs), and includes an increased contribution from cells in the midline thalamus, which could influence neocortical populations in preparation for the reactivation of hippocampal memory traces. Furthermore, the correlation between KCs and thalamic units can be modulated by CA1 ripples, suggesting that combined {\textquoteleft}neocortical KC+CA1 ripple{\textquoteright} events can reveal subtle interactions between the three regions. Lastly, units in the reuniens and the ventromedial nuclei show a broad decrease in spiking probability around the time of hippocampal ripples. 57.6\% of units in these nuclei present a significant drop in firing rate compared to 20.8\% in cells recorded in other midline nuclei (p\< 0.05; n=57 units). This suggests that certain thalamic nuclei may be key for gating the transfer of memory information from the hippocampus to neocortex, by opening a time window in which ripples may be more likely to occur.

These results provide the first evidence of the involvement of midline thalamic cells in neocortico-hippocampal interactions during sleep, and point to specific mechanisms by which multi-region brain interactions may contribute to the systems consolidation of memories.

}, author = {Varela, Carmen and Matthew A. Wilson} }