Dcf1 Triggers Dendritic Spine Formation And Facilitates Cognitive Behavior

Dendritic spines,a special kind of structure in nerve cells,play a key role in performing cellular function.Structural abnormalities of the dendritic spine may contribute to synaptic dysfunction and have been implicated in memory formation.However,the molecular mechanisms that trigger dendritic spine loss remain unclear.Here,we show that the absence of dendritic cell factor 1(Dcf1)appeared dendritic spines dysplasia,which in turn leads to the damage of learning and memory,In contrast,enhancing Dcf1 expression rescues dendritic spines morphology and function,indicating a pivotal role of Dcf1 in cellular function.Electrophysiological test indicates that there is a significant reduction in the frequency of miniature excitatory postsynaptic currents in Dcf1 knockout(KO)mice,indicating a reduction in the number of functional synapses in the hippocampus of KO mice.Subsequent to optogenetic ignition,we observed a weaker neuronal activation in Dcf1 KO mice,explaining the neural circuit cause.On molecular mechanism,we demonstrated an unprecedented discovery that Dcf1 triggers the dendritic spine and synaptic function and memory through the recruitment of Lcn2 and activation of PSD95-NMDAR signaling.Our results highlight an unexpected regulatory mechanism of dendritic spine development and learning and memory.Further we show that the loss of dendritic cell factor 1(Dcf1)in the nervous system of mice induces anxiety and social interaction deficiency,autism-like behavior.Electrophysiological tests indicate that there is a significant reduction in the amplitude of long-term potentiation in NKO mice,indicating a reduction of dendritic plasticity in NKO mice.Dopamine and dopamine receptor D1 agonist could rescue this social cognition phenotype,and improves short-term plasticity,revealing a notable role that dopamine system plays on the autism spectrum disorders and the key area is the hippocampus.This study presents a new genetic mechanism that affects social interaction and may provide a new way to improve positive social interaction and treat autism spectrum disorders.In general,previous research on Dcf1 gene is still relatively little,this paper throughly explored the function of Dcf1 in the nervous system using Dcf1 knockout mice and Dcf1 knockout in the nervous system mice,providing a new therapeutic method for the study of gene function and nervous system diseases.