Reduction in LFP cross-frequency coupling between theta and gamma rhythms associated with impaired STP and LTP in a rat model of brain ischemia

The theta-gamma cross-frequency coupling (CFC) in hippocampus was reported to reflect memory process. In this study, we measured the CFC of hippocampal local field potentials (LFPs) in a two-vessel occlusion (2VO) rat model, combined with both amplitude and phase properties and associated with short and long-term plasticity indicating the memory function. Male Wistar rats were used and a 2VO model was established. STP and LTP were recorded in hippocampal CA3-CA1 pathway after LFPs were collected in both CA3 and CA1. Based on the data of relative power spectra and phase synchronization, it suggested that both the amplitude and phase coupling of either theta or gamma rhythm were involved in modulating the neural network in 2VO rats. In order to determine whether the CFC was also implicated in neural impairment in 2VO rats, the coupling of CA3 theta–CA1 gamma was measured by both phase-phase coupling (n:m phase synchronization) and phase-amplitude coupling. The attenuated CFC strength in 2VO rats implied the impaired neural communication in the coordination of theta-gamma entraining process. Moreover, compared with modulation index (MI) a novel algorithm named cross frequency conditional mutual information (CF-CMI), was developed to focus on the coupling between theta phase and the phase of gamma amplitude. The results suggest that the reduced CFC strength probably attributed to the disruption of the phase of CA1 gamma envelop. In conclusion, it implied that the phase coupling and CFC of hippocampal theta and gamma played an important role in supporting functions of neural network. Furthermore, synaptic plasticity on CA3-CA1 pathway was reduced in line with the decreased CFC strength from CA3 to CA1. It partly supported our hypothesis that directional CFC indicator might probably be used as a measure of synaptic plasticity.