The Neural Network And Cellular Mechanism Of Postoperative Two-way Episodic Memory Disorder

Part Ⅰ: Altered functional connectivity within the default mode network in two animal models with opposing episodic memoriesObject: The aim of the present study was to study the functional connectivity within the default-mode network(DMN)in two animal models with opposing episodic memories,such as postoperative cognitive dysfunction(POCD)and posttraumatic stress disorder(PTSD)by using resting-state functional magnetic resonance imaging(rsf MRI).This study investigated whether functional connectivity within the DMN is changed between POCD and PTSD,which will provide scientific proof for the neural mechanisms underlying opposing episodic memories between POCD and PTSD.Method: In the present study,we used the retrosplenial cortex as a seed region to study the functional connectivity within the DMN in two animal models with opposing episodic memories,of which memory enhancement was induced by footshocks to mimic PTSD and memory decline induced by lipopolysaccharide(LPS)challenge to mimic POCD.Results: POCD and PTSD showed significant differences in episodic memories compared with the control group,with significantly decreased and increased contextual freezing time in the POCD and PTSD group,respectively.With regard to the imaging data,there were significant differences in the functional connectivity between the retrosplenial cortex and the medial prefrontal cortex(m PFC),insular lobe,left piriform cortex,left sensory cortex,and right visual cortex among the three groups(P < 0.05).Post-hoc comparisons suggested that the LPS group showed a significantly increased functional connectivity between the retrosplenial cortex and m PFC as compared with the control group(P < 0.05).Compared with the POCD group,the PTSD group displayed significantly decreased functional connectivity between the retrosplenial cortex and the right visual cortex,retrosplenial cortex,insular lobe,left piriform cortex,and left sensory cortex(all P < 0.05).Conclusion: Our study suggests that differences in functional connectivity within the DMN may underlie opposing episodic memories such as PTSD and POCD.Thus,rsf MRI is a useful technique to study the opposing episodic memories.Part Ⅱ: Altered intrinsic activity and functional connectivity in two animal models with opposing episodic memoriesObject: The aim of this section was to study the neural network alternations in postoperative cognitive dysfunction(POCD)and posttraumatic stress disorder(PTSD)by rsf MRI,which will provid deeper neural mechanism understanding of episodic memories.Method: POCD and PTSD animal models were established as described in the first section.The amplitude of low-frequency fluctuations(ALFF)of spontaneous blood oxygen level dependent signals was applied to assess regional disturbances in POCD and PTSD.Then,we examined whether the memory relevant brain regions with impaired ALFF altered functional connectivity within the whole brain.Results: Compared with control group,POCD had significantly decreased contextual freezing time while PTSD showed increased contextual freezing time in the fear conditioning test(P < 0.05).There were significant group differences in ALFF in the bilateral dentate gyrus,left auditory cortex,left somatosensory cortex,and left visual cortex(P < 0.05).Taken the dentate gyrus as seed,our study showed that footshocks induced significant decrease in functional connectivity between the left dentate gyrus and visual cortex when compared with the POCD group(P < 0.05).Notably,contextual freezing time was negatively associated with ALFF values in the left dentate gyrus(P < 0.05).Conclusion: Our data suggested that damaged regional spontaneous activity and abnormal functional connectivity might differently involve in the neural mechanism underlying neuropsychiatric disorders with opposing episodic memories,such as POCD and PTSD.Part Ⅲ: Role of parvalbumin interneuron and γ oscillation in two animal models with opposing episodic memoriesObject: It has been demonstrated that a subset of hippocampal neurons that express parvalbumin(PV)and its neural circuit γ oscillation play key roles in cognitive performance,whereas their dysfunctions have been linked to many neuropsychiatric disorders.This section aimed to investigate alternations of PV interneurons and γ oscillation in POCD and PTSD,and the relation between them.Method: POCD and PTSD animal models were established as described in the first section.At 7 days before model establishment,animals in each group underwent a chronic implant surgery.Twenty four hours after LPS injection or footshocks,local field potential recordings were performed when the animals were under anesthsia by Plexon(Plexon,USA).The neuroanatomy of PV interneurons in the hippocampus was determined by western blot analysis and immunofluorescence.Results: Compared with control group,POCD had significantly decreased while PTSD showed increased contextual freezing time in the fear conditioning test(P < 0.05).Compared with control group,POCD had significantly decreased high-expression PV interneurons and gamma oscillation while PTSD had increased high-expression PV interneurons and gamma oscillation in the dentate gyrus(P < 0.05).In addition,POCD had significantly increased high-expression PV interneuron in the CA1 and CA3 regions when compared with control group(P < 0.05).However,there was no difference in these two regions between control and PTSD groups(P > 0.05).Conclusion: Our study suggested that PV interneurons and γ oscillation might play a key role in POCD and PTSD,which might differently involve in the neural mechanism underlying neuropsychiatric disorders with opposing episodic memories.