Mesopontine median raphe regulates hippocampal ripple oscillation and memory consolidation

It has been suggested that hippocampal sharp-wave ripples (SWR) are important for memory consolidation. Here, the authors found that the activation of a non-serotoninergic subpopulation of median raphe neurons suppresses hippocampal sharp-wave ripples and impairs memory consolidation. These findings uncover a new brainstem influence on SWR and hippocampal memory function. Sharp wave–associated field oscillations (∼200 Hz) of the hippocampus, referred to as ripples, are believed to be important for consolidation of explicit memory. Little is known about how ripples are regulated by other brain regions. We found that the median raphe region (MnR) is important for regulating hippocampal ripple activity and memory consolidation. We performed in vivo simultaneous recording in the MnR and hippocampus of mice and found that, when a group of MnR neurons was active, ripples were absent. Consistently, optogenetic stimulation of MnR neurons suppressed ripple activity and inhibition of these neurons increased ripple activity. Notably, using a fear conditioning procedure, we found that photostimulation of MnR neurons interfered with memory consolidation. Our results demonstrate a critical role of the MnR in regulating ripples and memory consolidation.