Regulating Of Spatial Memory By The Postrhinal Cortex And Postrhinal Cortex–ventral Lateral Orbitofrontal Cortex Pathway

Part 1 The postrhinal cortex regulates spatial memoryBackground: Alzheimer disease(AD)is a neurodegenerative illness,clinical manifestations include deterioration of cognitive function,loss of self-sufficiency,and mental and behavioral disorders.It accounts for 60% to 80% of the dementia.Great efforts have been paid for earlier identification and treatment of AD,but they end in failure.Some research indicates that dysfunction of the postrhinal cortex(POR)may be an early symptom of AD,and lead to impairment of spatial memory.But the mechanism of this dysfunction is no clear.Purpose: Our study aims to dissect the POR in the spatial memory of mice,and lays a foundation for further research on early pathologic mechanisms of AD.Methods: We use immunofluorescence staining for cell type identification,in vivo optogenetic and electrophysiological methodologies with novel object place recognition,and c-fos staining to dissect the function of the POR in spatial memory.Results: Immunofluorescence staining results indicate there are GABAergic and glutamatergic neurons in the POR,cell quantification reveal that 45%± 0.7 of PORneurons are GABAergic,while 48.5% ± 1.6 are glutamatergic and 6.5%± 1.1 arecholinergic.In vivo optogenetic methodologies with novel object place recognitionexperiments and electrophysiological methodologies suggest inhibiting POR glutamatergic neurons or activating POR GABAergic neurons impairs the spatial memory retrieval of mice.Conclusion: The POR GABAergic and glutamatergic neurons both participate in the spatial memory retrieval,disproportionality of these activated neurons could lead to impairment of spatial memory retrieval.Part 2 The role of uncinate fasciculus in spatial memoryBackground: The uncinate fasciculus(UF)is a long-range white matter fiber tract in primates.The pathway(POR-vlOFC pathway)arising from the POR which projects to ventral lateral orbitofrontal cortex(vlOFC)may contribute to uncinate fasciculus functions in rodents.Previous studies have found that UF dysfunction is associated with spatial memory deficit in AD patients,but the UF exact function remains unclear,and it remains unknow how the UF participates in the spatial memory processing.Purpose: To further illuminate the UF function in spatial memory,we dissected the POR-vlOFC pathway of mice in the present study.Methods: We use cell-type-specific trackers to examine the structure of the POR-vlOFC pathway,in vivo optogenetic and electrophysiological methodologies with novel object place recognition,and c-fos staining to dissect the function of the POR-vlOFC pathway in spatial memory.Results: Anterograde tracing results indicate the POR-vlOFC pathway is glutamatergic structure,major terminal areas of the glutamatergic pathway from the POR also include dorsal hippocampal commissure(dhc)and laterodorsal thalamic nucleus(LD).In vivo optogenetic methodologies with novel object place recognition experiments suggest that there was no significant difference in memory performance between e Np HR3.0+ group and m Cherry+ group when the POR-dhc or POR-LD pathway was optically stimulated(Student's t-test.Figure 4c,dhc: t= 0.336,p= 0.744;LD: t=-0.212,p= 0.836).while inhibiting the POR-vlOFC pathway in recognition phase impairs the spatial memory retrieval of mice.Subsequent to behavioral testing,the level of activity-dependent c-fos expression in vlOFC was significantly lower in experimental group than control group.Using in vivo electrophysiological methodologies,activation or inhibition of this pathway with optogenetics technique can excite or inhibit the firing postsynaptic neurons in the vlOFC,respectively.Conclusion: The POR-vlOFC pathway is glutamatergic structure,and it regulates spatial memory retrieval specifically.