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bioRxiv · 10.1101/2024.07.19.604325

A distinct down state assembly in retrosplenial cortex during slow-wave sleep

Opalka, A. N.·Dougherty, K. J.·Wang, D. V.
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Abstract

Understanding the intricate mechanisms underlying slow-wave sleep (SWS) is crucial for deciphering the brains role in memory consolidation and cognitive functions. It is well-established that cortical delta oscillations (0.5-4 Hz) coordinate communications among various cortical, hippocampal, and thalamic regions during SWS. These delta oscillations have periods of Up and Down states, with the latter previously thought to represent complete cortical silence; however, new evidence suggests that Down states serve important functions for information exchange during memory consolidation. The retrosplenial cortex (RSC) stands out for its pivotal role in memory consolidation due to its extensive connectivity with memory-associated regions, although it remains unclear how RSC neurons engage in delta-associated consolidation processes. Here, we employed multi-channel in vivo electrophysiology to study RSC neuronal activity in freely behaving mice during natural SWS. We discovered that the RSC contains a discrete assembly of putative excitatory neurons ([~]20%) that initiated firing at SWS Down states and reached maximal firing at the Down-to-Up transitions. Therefore, we termed these RSC neurons the Down state assembly (DSA), and the remaining RSC excitatory neurons as non-DSA. Compared to non-DSA, DSA neurons exhibit a higher firing rate, larger cell body size, and no connectivity with nearby RSC neurons. Subsequently, we investigated RSC neuronal activity during a contextual fear conditioning paradigm and found that both DSA and non-DSA neurons exhibited increased firing activity during post-training sleep compared to pre-training sleep, indicating their roles in memory consolidation. Lastly, optogenetics combined with electrophysiology revealed that memory-associated inputs differentially innervated RSC excitatory neurons. Collectively, these findings provide insight on distinct RSC neuronal subpopulation activity in sleep and memory consolidation.

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Opalka, A. N., Dougherty, K. J., Wang, D. V.. 2024-07-23. A distinct down state assembly in retrosplenial cortex during slow-wave sleep. https://doi.org/10.1101/2024.07.19.604325

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