Prefrontal cortex down states can be triggered by CA1 stimulation and are enhanced by long-term potentiation in urethane-anesthetized rats

Slow waves are the main oscillatory activity during non-rapid eye movement sleep, playing a crucial role in synaptic homeostasis, memory consolidation, and cortical network regulation. In urethane-anesthetized rodents, frequently used in long-term potentiation experiments in vivo, brain activity alternates between a deactivated state, dominated by slow waves, and an activated state characterized by faster oscillations. However, the interplay between synaptic plasticity and slow wave dynamics within these fluctuating brain states remains unclear. Here, we investigated whether long-term potentiation in the hippocampal-medial prefrontal cortex (CA1-mPFC) circuit, critical for memory processing, modulates cortical slow wave dynamics during urethane anesthesia. Electrical stimulation of CA1 robustly evoked a transient (50 to 200 ms) event of population silence (down states) in the medial prefrontal cortex, which emerged after the typical evoked field post-synaptic potential, and was consistently associated with a slow waves. Importantly, long-term potentiation induction significantly enhanced the CA1-evoked medial prefrontal cortex down states and slowed spontaneous cortical slow wave oscillations, without altering the activated/deactivated brain state proportion. Our findings provide direct evidence of an interaction between synaptic plasticity and cortical slow wave dynamics, laying the groundwork for future studies on the underlying mechanisms of state-dependent synaptic homeostasis.