Modulating Methods And Mechanisms Of Magnetic Stimulation On The Electrical Activities In Rat Hippocampus

The synaptic electrical activity in CA1 region of hippocampus is closely related to learning and memory and abnormal synchronous discharge activity in CA3 region is the source of epilepsy.Clinical trials have shown that magnetic stimulation can effectively reduce the symptoms of neurological diseases by regulating the electrical activity of hippocampal neurons.However,the spatial resolution of traditional magnetic stimulation is low,so it is difficult to accurately locate the therapeutic target,and the best method of magnetic stimulation regulation and its mechanism of action on hippocampal electrical activity are not clear.In view of the above problems,the main research work of this thesis is as follows:(1)In this thesis,a novel transplantable"on-line magnetic stimulation"device was proposed and designed,which can match patch clamp platform and multi electrode array platform to realize real-time synchronization of magnetic stimulation and electrophysiological recording of hippocampal slices.The effectiveness and reliability of the device are verified by simulation and animal experiments.(2)In this thesis,the regulations of pre magnetic stimulation(adding magnetic stimulation before the intervention of normal electrical activity in hippocampus)and post magnetic stimulation(adding magnetic stimulation after the intervention of normal electrical activity in hippocampus)on synaptic plasticity(LTP)in hippocampal Schaffer-CA1 pathway and epileptic discharge activity in hippocampal CA3 region of rats were investigated.The results show that magnetic stimulation can reduce LTP level and inhibit epileptiform discharge activity,and this regulatory effect is dependent on magnetic stimulation mode(frequency,waveform,intensity and duration).(3)In this thesis,combined with pharmacological and electrophysiological experiments,different control groups,drug groups and magnetic stimulation groups were designed to study the mechanism of magnetic stimulation on the regulation of electrical activity in hippocampus before and after the addition of receptor antagonist.The results suggest that the regulation of LTP maintenance by magnetic stimulation is related to AMPA receptor(α-amino-3-hydroxy-5-methyl-4-isoxazol propionic acid receptor),while the regulation of epileptiform discharge by magnetic stimulation is related to GABA_Areceptor(γ-aminobutyric acid type A receptor).(4)In this thesis,a submillimeter size micro magnetic stimulation device with small size,high resolution and low power consumption was designed,and the key problems such as biocompatibility and safety were solved.The device can be placed in the hippocampal brain sub region with a spatial resolution of mm.The experimental results show that it can specifically inhibit epileptiform discharges.In this thesis,the design of"instant magnetic stimulation+electrical signal synchronous observation"device,the regulation mode of magnetic stimulation and the improvement of spatial resolution of magnetic stimulation were proposed,and the regulation and mechanism of different strategies of magnetic stimulation on hippocampal discharge were explored.The research results of this thesis provide a new idea for the basic research of magnetic stimulation in neuroscience or neurophysiology,and provide a theoretical basis and data accumulation for the clinical application of magnetic stimulation in the treatment of neurodegenerative diseases.