| Background: Maternal behavior is a special social behavior,which is also the first link and template for children to learn social behavior.Using rodents to study maternal behavior can provide references for relevant diseases.Previous studies have shown that the maternal behaviors in mice include lactation,sniffing,retrieving,crouching,and pup grooming.The goal of maternal behavior is to improve the living conditions of the offspring for ensuring the successful transmission of their genes.Therefore,maternal behavior is very important for the growth and development of pups.Any deviation from normal maternal behavior may lead to mental illness in both the mother and her offspring.Previous research has indicated that the medial preoptic area of the hypothalamus(MPOA)serves as a central brain region responsible for coordinating parenting motivation,hormonal changes,and parenting behavior.It is activated after maternal behavior.And either chemogenetics or optogenetics regulation of MPOA can affect maternal behavior.Previous works indicate that there are significant differences in maternal behavior between mother mice(Mm)with reproductive experience and virgin mice(Vm)without sexual or reproductive experience.On the one hand,this difference is caused by changes in various hormone levels in the body.During early pregnancy,the mother gradually increases her hormone levels and maintains a stable and relatively high level until delivery.In addition,after Virgin mice stay with Mother mice and babies(Vb),the release of oxytocin was increased and the maternal behavior of virgin mice was enhanced due to the learning of maternal behavior of mother mice and the stimulation of ultrasonic stimulation of pups.On the other hand,maternal behavior is closely related to reproductive experience,and postpartum female mice are relatively experienced in rearing babies.The neuron is the basic functional unit of the nervous system,and all behaviors depend on the regulation of neuron electrical activity.Therefore,we wanted to investigate whether the electrical activity of MPOA neurons in Mm is different from Vm female mice and whether the changes in hormone levels affect the excitability of MPOA neurons.What changes can the maternal behavior of mentally abnormal mother mice occur? To this end,the present study also explored changes in maternal behavior in mothers with autism spectrum disorder(ASD),a typical model of social behavior disorders.ASD is a neurodevelopmental disorder characterized by difficulties in social communication and repetitive behaviors.Previous research has primarily focused on the mechanisms of social communication dysfunction among autistic patients,but less on maternal behavior as a special social behavior.As mentioned earlier,maternal behavior plays a crucial role in infants’ healthy development and growth.In the second part of our study,we utilized a mouse model of autism induced by the deletion of a single gene-Shank3 KO(Shank3 knockout,KO)-to investigate potential alterations in maternal behavior.Objectives:What are the effects of maternal reproductive experience on the excitability of MPOA neurons in mice? What are the potential channel mechanisms and hormone regulatory effects? In the KO maternal mice model,are there any abnormalities in maternal behavior.Methods: 1.Female mice picking up and taking care of the pups were recorded in the soundproof box,as well as ultrasonic recordings of both mother mice and pups.2.The excitability,after hyperpolarized potential and calcium-dependent potassium channel currents of MPOA neurons on Mm,Vm and Vb coronal films were compared by whole-cell patch clamp combined with pharmacology.To explore the effect of oxytocin on the excitability and ion channel of MPOA neurons.3.The mother mice retrieving and caring for their pups were recorded in the sound isolation box and the open field respectively,and the ultrasound of mother mice and pups were recorded at the same time.Results: 1.Compared to Mm,Vm exhibits less maternal care behavior towards pups.There is no significant difference in the number of ultrasound calls or the duration of vocalizations of pups.2.The average firing frequency of MPOA neurons from Mm group was decreased compared with Vm group.It is caused by the increased amplitude of the afterhyperpolarization potential(AHP)which is mediated by small conductance calciumactivated potassium channels(SK).3.Vb showed significantly increased caring behavior to pups than Vm.The amplitude of AHP was increased and the average frequency of repeated discharge decreased in the Vb group compared with that of Vm group.Vm MPOA neurons displayed an increase in AHP amplitude and a decrease in discharge frequency following perfusion of an oxytocin agonist.Conclusion:1.The excitability of Mm MPOA neurons was lower than that of Vm.This was due to an increase in afterhyperpolarization(AHP)amplitude,which was mediated by small conductance calcium-activated potassium channels(SK).2.The change of AHP in Mm MPOA neurons may be related to the release of oxytocin.3.The maternal behavior of female KO mice in cared for their offspring decreased compared to female WT mice.4.The speed at which female KO mice carry their offspring in their mouths increased compared to female WT mice.This may be due to an increased aversion to their offspring,but further confirmation is required. |
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