人工冬眠揭示功能性与病理状态转变中不同的相互作用动态

Neural population activity can reorganize without disrupting function, but how such changes differ from those associated with pathology remains unknown. Artificial hibernation, Q-neuron-induced hypothermia and hypometabolism (QIH), causes extensive synaptic remodeling in the hippocampus without erasing established memories, allowing us to examine how extensive network reorganization can occur without lasting functional impairment. Longitudinal calcium imaging showed that hippocampal activity recovered after QIH without returning to its pre-hibernation population configuration. Instead, QIH reorganized neuronal activity patterns and coactivity beyond representational drift. Electrophysiological recordings revealed that this reorganization of neuronal interactions depended on the preceding network state. In mice subjected to kainic acid-induced status epilepticus, QIH reduced seizure-associated increases in neuronal interactions and spike coactivity during sharp-wave ripples. Over the following 50 days, the divergence of hippocampal LFP trajectories was constrained, and the progressive development of electrophysiological and histological pathology was attenuated. These findings suggest that controlled, extensive reorganization of neural population activity can prevent the progression toward pathological network states, with changes in neuronal interactions, particularly sharp-wave ripple-associated coactivity, accompanying this process.

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