The Simulation Study Of Single Neuron Firing In Hippocampal CA1 And CA3

Objective:Hippocampus is the limbic system, the dischagre activity of Hippocampal neurons and the memory function of the brain, emotional behavior and seizures are closely related. Up to date, most studies are focused on the Hippocampal CA1 and CA3, different firing patterns carry different signals, so the study of firing patterns of neurons has a significant sense for neural information coding. Firing frequency and the number of peak discharge in each of the bursting are important indicators to measure the discharge mode. The aim of this study is to analyze the variability of firing patterns and firing frequencies in Hippocampal CA1 and CA3 by modeling and simulation.Methods:1. The modeling and simulation of the Hippocampal CA1 single neuron:A 16-compartment cable model of a Hippocampal CA1 neuron is developed based on the Warmam model. The dendrites contain no active channels, but five active channels are contained in soma (INa,INap, IDR, IA, IM).In this model, the calcium currents and potassium currents (ICa,ICT and IAHP) regulated by calcium concentration are not included.2. The modeling and simulation of the Hippocampal CA3 single neuron:This paper uses a reduced Traub model which contains only the soma compartment and the dendrite compartment. Soma has sodium (INa) and potassium delayed-rectifier (IK-DR) currents; dendrite has calcium (ICa), Ca activated potassium (IK-C), potassium afterhyperpolarization (IK-AHP) and synapyic (ISyn) currents.3. Analyze the variability of firing frequencies and firing patterns of a single neuron with the changes of extracellular potassium concentration and ion channel conductances through the modeling and simulation of the single neuron in Hippocampal CA1.4. Analyze the variability of firing frequencies and firing patterns of a single neuron with the changes of external stimulus and electrotonic coupling through the modeling and simulation of the Hippocampal CA3 single neuron.Results:1. Simulation results show that the neuron can generate periodic spontaneous firing activity in Hippocampal CA1 single neuron. The spiking frequency increases with increasing [K+]。, sodium conductance and decreasing potassium conductances. Single neuron activity appears in singlets or is grouped into bursts of two or three spikes.INa has an important influence on spontaneous bursting, an increased INa alone can be sufficient to sustain spontaneous bursting.2. Simulation results show that (1) the firing patterns of the model of Hippocampal CA3 single neuron can be divided into five categories:very low frequency bursting (VLF bursting), low frequency bursting (LF bursting), high frequency soma spiking, soma-dendritic spiking and complex mode; (2) In Hippocampal CA3 single neuron model, when gc=0mS/cm2, there is no bursting. As isolated soma current Is is increased, the spiking frequency increases and the firing pattern is somatic Na spike; as isolated dendrite current Id is increased, the spiking frequency increases and the firing pattern is Ca spike. When gc=2.1mS/cm2, as steady somatic current Is is increased, the spiking frequency increases and there is a transition from resting to periodic VLF bursting to somatic spiking to steady depolarization; for increasing steady dendritic input current Id, the spiking frequency increases and there is a progression from resting to VLF bursting to LF bursting to steady depolarization. When gc=∞mS/cm2, the soma and dendrite compartment was combined one compartment model, as current Is (Id) is increased, the spiking frequency increases and the firing pattern is Na-Ca spike, there is no bursting.Conclusions:1. The hippocampal CA1 single neuron can generate periodic spontaneous firing activity. The variability of spontaneous firing frequencies and firing patterns of single neuron are relevant to [K+]。and ion channel conductances. The spiking frequency increases with increasing [K+]。, sodium conductance and decreasing potassium conductances. Single neuron activity appears in singlets or is grouped into bursts of two or three spikes, with complex mode.2. The firing patterns of Hippocampal CA3 single neurons are closely related to external stimulus and electrotonic coupling gc. As external current is increased, the spiking frequency of Hippocampal CA3 single neuron increases and the firing patterns change with the electrotonic coupling gc. When gc=0mS/cm2 or gc=∞mS/cm2, there is no bursting.