Mechanism Of Cognitive Mediated By Hippocampal-Cortical Neural Circuit

Social recognition memory(SRM),the ability to recognize and memorize another individual’s familiarity,reproductive status and relatedness,enable members spend more time on activities related to group management and protection,is essential for group reproduction and survival.As a critical process of social behavior,impairment of SRM usually leads to social behavioral defect.Neurodevelopmental disorders such as autism spectrum disorder(ASD)and intellectual disability are characterized by defective social behaviors.Therefore,understanding of the formation mechanism of social recognition memory is important for the development of individuals and population reproduction.The generation of SRM relies on the coordination of precise brain region circuits and functional synapse formation.Recent studies have identified multiple brain regions for social behaviors,such as social interaction and social recognition memory.These studies mainly focus on uncovering the function of a special nucleus for single social behavior.The distinct brain regions involved in different social behaviors and the underlying-structure molecular mechanism mediating the SRM still remain unclear.In our previous study,we identified a scaffold protein Lnx1 containing PDZ domains specifically expressed in postsynaptic densities(PSDs)of hippocampal CA3 neurons.Deletion of Lnx1 causes defective synaptic arrangement and further disrupts the hippocampal DG-CA3 neural circuits,suggesting a critical role of Lnx1 in the neural development and synaptic plasticity,and thus regulates cognition and memory of hippocampus.Therefore,we attempt to explore the role of Lnx1 in social recognition memory.In this study,we used WT mice and Lnx1-/-mice as the research objects to observe the differences of behavior and activated brain regions during the process of social recognition memory,and further uncovered the mechanism of Lnx1 mediated social recognition memory for a greater understanding of the brain functions and corresponding behaviors.Our results identify that the neurons of CA3 and CA1 areas are strongly involved in the process of social recognition memory,which relies on the critical role of Lnx1-NMDAR functional complex mediated synaptic function during adolescent period.The relationship and influence of emotion for learning cognition need further research.There is a long preclinical period for Alzheimer’s disease(AD)before cognitive impairment.Neuropsychiatric symptoms(NPS)such as depression,anxiety,apathy,and irritability occur very early and in prodromal phases of clinical Alzheimer’s disease(AD),which might be an increased risk for later developing AD.Here we treated young APP/PS1 AD model mice prophylactically with serotonin-selective re-uptake inhibitor(SSRI)paroxetine and investigated the protective role of anti-depressant agent in emotional abnormalities and cognitive defects during disease progress.Our data indicate that prophylactic administration of paroxetine ameliorates the emotional abnormality and memory deficit in AD mice.These neuroprotective effects are attributable to functional restoration of glutamate receptor in AD mice.