Haseeb Javed: cFos principal cells and interneurons are strongly reactivated by sharp wave ripples

How our subjective experiences are stored in objective biological tissue is one of the major unanswered questions in nature. Select networks of neurons that are co-active during an experience are believed to store the memory of that experience. These neurons, called the Memory Engram, express the cFos immediate early gene (IEG) in the hippocampus, amongst other areas of the brain. Secondly, fast oscillating brain waves in the hippocampus called Sharp Wave Ripples (SWRs) are implicated in the consolidation of memories via the reactivation of the experience neurons during sleep and rest. However, there is no experimental evidence investigating the relationship between these two mechanisms, which are important in the encoding and consolidation of spatial memories.

 

Here we exposed cFos-tTA mice to two novel environments and recorded extracellular unit and local field potential (LFP) activity in the dorsal CA1. The mice were placed back in the environments and tetrodes were lowered daily for several days while activity was recorded as the mice became familiar with the environments. cFos principal cells showed significant SWR reactivation during post-learning rest compared to non-cFos principal cells. Pairs of cFos principal cells also had significantly higher SWR co-activation compared with chance baseline, and compared with non-cFos principal cell pairs. cFos interneurons also increased their participation in SWRs compared to non-cFos interneurons. cFos place cells had larger place fields and carried less spatial information than non-cFos place cells, but had similar stability and remapping across environments. Lastly, cFos principal cells and interneurons had stable SWR reactivations over several days.

 

Together, our results identify for the first time using in vivo electrophysiology, the significant relationship between the cFos memory engram and sharp wave ripples.