Defects Of Synaptic Transmission And Plasticity In Hippocampal CA1Neurons Of Transferring Receptor (TfR1) Knock-out Mice

Transferrin receptors exist in many cells’ surface. Two types of transferrin receptors have been found in organisms, one is transferrin receptor1(TfR1) and the other one is transferrin receptor2(TfR2). The former widely distributes in the brain while the latter is rare, so we focus to the research of TfR1. The main function of TfR1in organism is that it can deliver ferroprotein into cells from outside of the cells. For example, in central nervous system (CNS), TfR1-mediated endocytosis transfers transferring (Tf)-iron complex to intracellular. Thus it can regulate the growth of cell. But its effect on neurons synaptic transmission and synaptic plasticity is not clear at present. As the major contact point and communication place between neurons, the synapse is regarded as the major location where learning and memory happen. The efficiency of synaptic transmission can be modified, so we called it as synaptic plasticity, which could persist from several hours to several days. Schaffer collateral of CA3pyramidal cells (CA3) receives inputs from CA1pyramidal cells (CA1). This circuit involves into many physiologic processes and is regarded as the major location where synaptic plasticities in hippocampal of cerebral happen. In this dissertation, in order to obtain a breakthrough on the function of TfRl in CNS, we investigated whether TfR1could affect synaptic transmission and plasticities by fEPSP and whole cell patch clamp techniques using the CA1-CA3circuit of hippocampal model.In our experiment, we detected the synaptic transmission, receptor expression and long term synaptic plasticity of CA1vertebral neurons in hippocampal area of conditional knock-out Nestin Cre-TfR1mouse. The results showed that glutamatergic presynaptic release rate decreased after TfR1knocking out. Although postsynaptic current declined, the ratio between postsynaptic NMDA receptor and AMPA receptor did not change. Furthermore, we recorded the long term potentiation (LTP) induced by100Hz (HFS) and TBS stimulation in CA1, and found that both LTP in TfR1knockout animals were down. So we concluded that TfRl played an important role in the growth of hippocampal CA1neurons.