AbstractNeurons fire at highly variable innate rates and recent evidence suggests that low and high firing rate neurons display different plasticity and dynamics. Furthermore, recent publications imply possibly differing rate-dependent effects in hippocampus versus neocortex, but those analyses were carried out separately and with possibly important differences. To more effectively synthesize these questions, we analyzed the firing rate dynamics of populations of neurons in both hippocampal CA1 and frontal cortex under one framework that avoids pitfalls of previous analyses and accounts for regression-to-the-mean. We observed remarkably consistent effects across these regions. While rapid eye movement (REM) sleep was marked by decreased hippocampal firing and increased neocortical firing, in both regions firing rates distributions widened during REM due to differential changes in high-firing versus low-firing cells in parallel with increased interneuron activity. In contrast, upon non-REM (NREM) sleep, firing rate distributions narrowed while interneuron firing decreased. Interestingly, hippocampal interneuron activity closely followed the patterns observed in neocortical principal cells rather than the hippocampal principal cells, suggestive of long-range interactions. Following these undulations in variance, the net effect of sleep was a decrease in firing rates. These decreases were greater in lower-firing hippocampal neurons but higher-firing frontal cortical neurons, suggestive of greater plasticity in these cell groups. Our results across two different regions and with statistical corrections indicate that the hippocampus and neocortex show a mixture of differences and similarities as they cycle between sleep states with a unifying characteristic of homogenization of firing during NREM and diversification during REM.Significance StatementMiyawaki and colleagues analyze firing patterns across low-firing and high-firing neurons in the hippocampus and the frontal cortex throughout sleep in a framework that accounts for regression-to-the-mean. They find that in both regions REM sleep activity is relatively dominated by high-firing neurons and increased inhibition, resulting in a wider distribution of firing rates. On the other hand, NREM sleep produces lower inhibition, and results in a more homogenous distribution of firing rates. Integration of these changes across sleep results in net decrease of firing rates with largest drops in low-firing hippocampal pyramidal neurons and high-firing neocortical principal neurons. These findings provide insights into the effects and functions of different sleep stages on cortical neurons.
Reduced firing rates of pyramidal cells in the frontal cortex of APP/PS1 can be restored by acute treatment with levetiracetam
