RESUMEN
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. 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 through the recruitment of Lcn2 and activation of PSD95-NMDAR signaling. Removing this brake leads to memory damage. Our results highlight an unexpected regulatory mechanism of dendritic spine development and formation.
Asunto(s)
Espinas Dendríticas/metabolismo , Hipocampo/metabolismo , Proteínas de la Membrana/metabolismo , Memoria , Proteínas del Tejido Nervioso/metabolismo , Animales , Corteza Cerebral/metabolismo , Corteza Cerebral/ultraestructura , Espinas Dendríticas/ultraestructura , Homólogo 4 de la Proteína Discs Large/metabolismo , Potenciales Postsinápticos Excitadores , Lipocalina 2/metabolismo , Proteínas de la Membrana/deficiencia , Ratones Noqueados , Proteínas del Tejido Nervioso/deficiencia , Receptores de N-Metil-D-Aspartato/metabolismo , Transducción de Señal , Proteína de Unión al GTP rac1/metabolismoRESUMEN
Deficits in social interaction are hallmarks of neurological and psychiatric disorders. However, its underlying mechanism is still unclear. Here, we show that the loss of dendritic cell factor 1 (Dcf1) in the nervous system of mice induces social interaction deficiency, autism-like behaviour, and influences social interaction via the dopamine system. Dopamine receptor D1 agonist rescues this social cognition phenotype, and improves short-term plasticity. Together, 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.
Asunto(s)
Relaciones Interpersonales , Proteínas de la Membrana/fisiología , Proteínas del Tejido Nervioso/fisiología , Receptores de Dopamina D1/fisiología , 2,3,4,5-Tetrahidro-7,8-dihidroxi-1-fenil-1H-3-benzazepina/administración & dosificación , Animales , Dopamina/administración & dosificación , Dopamina/metabolismo , Agonistas de Dopamina/administración & dosificación , Potenciales Postsinápticos Excitadores , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Hipocampo/fisiología , Masculino , Proteínas de la Membrana/genética , Ratones Endogámicos C57BL , Ratones Noqueados , Proteínas del Tejido Nervioso/genética , Plasticidad Neuronal , Receptores de Dopamina D1/metabolismoRESUMEN
Under the new Hölder conditions, we consider the convergence analysis of the inverse-free Jarratt method in Banach space which is used to solve the nonlinear operator equation. We establish a new semilocal convergence theorem for the inverse-free Jarratt method and present an error estimate. Finally, three examples are provided to show the application of the theorem.