Brain state-dependent neocortico-hippocampal network dynamics are modulated by postnatal stimuli.

Abstract

Neurons in the cerebral cortex and hippocampus discharge synchronously in brain state-dependent manner to transfer information. Published studies have highlighted the temporal coordination of neuronal activities between the hippocampus and a neocortical area, however, how the spatial extent of neocortical activity relates to hippocampal activity remains partially unknown. We imaged mesoscopic neocortical activity while recording hippocampal local field potentials in anesthetized and unanesthetized GCaMP-expressing transgenic mice. We found that neocortical activity elevates around hippocampal sharp wave ripples (SWR). SWR-associated neocortical activities occurred predominantly in vision-related regions including visual, retrosplenial and frontal cortex. While pre-SWR neocortical activities were frequently observed in awake and natural sleeping states, post-SWR neocortical activity decreased significantly in the latter. Urethane anesthetized mice also exhibited SWR-correlated calcium elevation, but in longer time scale than observed in natural sleeping mice. During hippocampal theta oscillation states, phase-locked oscillations of calcium activity were observed throughout the entire neocortical areas. In addition, possible environmental effects on neocortico-hippocampal dynamics were assessed in this study by comparing mice reared in ISO (isolated condition) and ENR (enriched environment). In both SWR and theta oscillations, mice reared in ISO exhibited clearer brain state-dependent dynamics than those reared in ENR. Our data demonstrate that the neocortex and hippocampus exhibit heterogeneous activity patterns that characterize brain states, and postnatal experience plays a significant role in modulating these patterns.Significant Statement The hippocampus is a center for memory formation. However, the memory formed in the hippocampus is not stored forever, but gradually transferred into the cerebral cortex synchronized activities between the neocortex and hippocampus has been hypothesized (for hippocampus-independent memory see (Sutherland and Rudy, 1989)). However, spatio-temporal dynamics between hippocampus and whole neocortical areas remains partially unexplored. We measured cortical calcium activities with hippocampal electroencephalogram (EEG) simultaneously and found that the activities of widespread neocortical areas are temporally associated with hippocampal EEG. The neocortico-hippocampal dynamics is primarily regulated by animal awake/sleep state. Even if similar EEG patters were observed, temporal dynamics between the neocortex and hippocampus exhibit distinct patterns between awake and sleep period. In addition, animals' postnatal experience modulates the dynamics.