Compartment Models Of Unipolar Brush Cells Based On Cell Characteristics

With the in-depth research and development of brain science,the functions of the cerebellum in terms of cognition,memory and motion control have gradually been understood.Recent studies have shown that unipolar brush cells in the cerebellar granule layer play a key role in controlling and consolidating cerebellar motor learning.The responsiveness and discharge pattern of unipolar brush cell synapses depend on the intrinsic electrical response characteristics of the cells,thus establishing computational models of unipolar brush cells to study its electrical response characteristics helps to understand cerebellar function further.This thesis focuses on computational models and electrical response characteristics of unipolar brush cells.The research content mainly includes:(1)Combining the characteristics of cell ion channels,by fitting the experimental physiological data of unipolar brush cells,a complete single compartment model and a minimal single compartment model for unipolar brush cells were proposed,and cell stable status and electrical response were analyzed based on these two models.First,the steady-state characteristics of unipolar brush cells were studied.The effects of the intrinsic properties of ion channels on cell dynamics were investigated by comparing two models.The results show that T-type calcium channels and inward rectifier potassium channels play an essential role in maintaining the stability of resting potential.Then,the return-type discharge characteristics of unipolar brush cells were studied,and the voltage responses of the two models at the input of the inhibitory m Glu R2 current were tested.The results showed that the T-type calcium channel is the primary ion channel for inducing the return-type discharge.Finally,the resonance characteristics of the cells were studied,and the results showed that the subthreshold resonance could be generated when the model inputs the ZAP current.The experimental results of the models are consistent with the physiological experiment results and the physiological characteristics of unipolar brush cells.(2)Since the single compartment model proposed above does not consider the influence of cell morphology on the electrical response characteristics,in order to better reflect the electrophysiological properties of unipolar brush cells,a detailed compartment model of unipolar brush cells based on the morphological structure is proposed.The model reconstructs cellular geometry based on the distribution of ion channels in physiology while constructing multiple types of stimulation sequences.The experimental results show that the detailed compartment model of unipolar brush cells can generate regular spikes when inputting depolarization step current stimulation while the peak after a sag is generated when feeding the hyperpolarization step current stimulus.Besides,when the sinusoidal current stimulation with linear or non-linear frequencies is inputted into the model,it can produce subthreshold resonance in which the resonance amplitude is smaller than that of the single compartment model,and the potential stabilization process is relatively gentle.Also,when the input is the Poisson stimulation,common spikes are generated,and the output spike frequency is approximately positively correlated with the input Poisson stimulation frequency and the number of synapses.The electrical response characteristics of the proposed model are consistent with physiological experimental results and the physiological characteristics of the cells.In conclusion,the thesis proposes a single compartment and detailed compartment model of unipolar brush cells based on the ion channel and morphological structure of unipolar brush cells.The proposed two models remain the fundamental physiological characteristics of cells by reconstructing cellular ion channels and morphological structures and effectively simulate the electrical response characteristics of unipolar brush cells.