Research On NMDA Receptor-mediated Response Mechanism Of Purkinje Cell

Purkinje cells receive stimulus inputs from parallel fibers and integrate information through synapses.Normally,we think only AMPA receptor expression at the synapses affects the discharge of Purkinje cells.However,recent research found that NMDA receptors also exist at the synapses,but fail to clearly reveal how they affect the discharge of Purkinje cells.Therefore,this thesis focuses on the mechanism of NMDA receptor-mediated Purkinje cell response,and the main contents are as follows:(1)This thesis first analyses the role of NMDA receptors in the discharge response of Purkinje cells and studies the Purkinje cell model based on NMDA receptor expression.This model introduces NMDA receptors in the traditional Purkinje cell model to receive stimulus signals from parallel fibers and produces simple spikes via Purkinje cell dendrite and soma processing.Afterward,we analyze the effects of NMDA receptors from the perspectives of simple spike frequency coding,time coding,and phase modulation by considering the stimulus pattern and the intensity changes of NMDA receptors.The experimental results show that NMDA receptors increase the discharge rate of Purkinje cells under low-frequency Poisson stimulation and inhibit the discharge rate under high-frequency Poisson stimulation.In addition,NMDA receptor expression can reduce the dispersion and increase the local regularity of the discharge sequences.Finally,NMDA receptors lead to the simple spike phase advance of Purkinje cells under sinusoidal input.(2)The discharge mechanism of Purkinje cells is not only related to synaptic inputs but also is regulated by the intrinsic characteristics of neurons.In view of this,this thesis considers the inherent computational characteristics of neurons and explores the inhibitory properties of NMDA receptors in the discharge of Purkinje cells in terms of the dendritic ion current and synaptic distribution locations.The experimental results show that high threshold calcium-activated potassium channels and delayed rectifying potassium channels are the key ion channels causing NMDA receptors to inhibit the discharge of Purkinje cells.The low conductance of the high threshold calcium-activated potassium channel results in the continuous saturation of the current in the delayed rectifying potassium channel,and thus enable Purkinje cells fail to discharge as normal.Moreover,synaptic distributed locations can affect the inhibitory effect of NMDA receptors on the discharge of Purkinje cells.The closer the NMDA receptors exist near the soma or the dendrites with large diameters,the stronger its inhibitory effects are.In summary,by constructing Purkinje cell model based on NMDA receptor expression,this thesis not only analyzes the mechanism of NMDA receptors in the discharge response of Purkinje cells in the aspects of the frequency coding,time coding,and phase modulation but also explores the biological basis of NMDA receptor inhibition based on the inherent computational properties of neurons.This study is helpful to further understand the information transmission between Purkinje cells and parallel fibers,and thus enrich the mechanism of synaptic integration in cerebellar information transmission.