Synapse-specific modulation of synaptic responses by brain states in hippocampal pathways.

Synaptic changes play a major role in memory processes. Modulation of synaptic responses by brain states remains however poorly understood in hippocampal networks, even in basal conditions. We recorded evoked synaptic responses at five hippocampal pathways in freely moving male rats. We showed that, at the perforant path to dentate gyrus (PP-DG) synapse, responses increase during wakefulness compared to sleep. At the Schaffer collaterals to CA1 (SC-CA1) synapse, responses increase during non-REM sleep (NREM) compared to the other states. During REM sleep (REM), responses decreased at the PP-DG and SC-CA1 synapses compared to NREM, while they increased at the fornix to nucleus accumbens synapse (Fx-NAc) during REM compared to the other states. In contrast, responses at the fornix to medial prefrontal cortex synapse (Fx-PFC) and at the fornix to amygdala synapse (Fx-Amy) were weakly modulated by vigilance states. Extended sleep periods led to synaptic changes at PP-DG and Fx-Amy synapses but not at the other synapses. Synaptic responses were also linked to local oscillations and were highly correlated between Fx-PFC and Fx-NAc but not between Fx-Amy and these synapses. These results reveal synapse specific modulations that may contribute to memory consolidation during the sleep-wake cycle. SIGNIFICANCE STATEMENT: Surprisingly, the cortical network dynamics remains poorly known at the synaptic level. We tested the hypothesis that brain states would modulate synaptic changes in the same way at different cortical connections. To tackle this issue, we implemented an approach to explore the synaptic behavior of five connections upstream and downstream the rat hippocampus. Our study reveals that synaptic responses are modulated in a highly synapse-specific manner by wakefulness and sleep states as well as by local oscillations at these connections. Moreover, we found rapid synaptic changes during wake and sleep transitions as well as synaptic down and upregulations after extended periods of sleep. These synaptic changes are likely related to the mechanisms of sleep dependent memory consolidation.