A Research On The Resonance Phenomenon And Its Mechanism In Rat Substantia Nigra Compacta Dopaminergic Neurons

Neural oscillation activity is the feature of neural network on physiological state.Different neuron resonance characteristics are the basic of neural networkresonance. Oscillatory electrical activity is the periodic changes of electricalcurrent, which can be divided into two types: synchronous oscillation andasynchronous oscillation. Synchronous oscillation is an operational oscillationwhich could keep stable synchronizing to the input stimulation. In contrast,asynchronous oscillation is characterized by the loss of synchronization and thuscannot oscillate to the input stimulation. Resonance is a phenomenon thatdescribes the frequency-selective ability of neurons to respond the input signal.Frequency selectivity represents an intrinsic property of neurons. Resonance andfrequency selectivity of neurons are very important because they serve as an important basis for coordinating network activity in the brain. Besides, they playa vital role in the information transmission among the neurons. Dopaminergicneuron is the main neuron of the substantia nigra compacta components. It hassignificant functions in processing the information of basal ganglia structuresand the output of dopaminergic neuron, referring to many physiologicalfunctions of the substantia nigra compacta, such as moving, learning andmemory. At present, Pathological synchronous oscillation has been observed inthe Parkinson’s disease patients, and the main symptom is excessivesynchronization oscillation. Synchronous oscillation theory is thought to beclosely related to information detection, analysis and integration. And the theorymight be the internal mechanism of the sensational and movement informationdisorder and thus leading to different clinical symptoms of the Parkinson’sdisease.“Oscillation model” is one of newly raised pathogeneses of the PD.However, the pathogenesis of PD remains unclear. In addition, clinical and basicstudies show that the pathological changes of dopaminergic neuron in thesubstantia nigra compacta have involved in the emergence and development ofvariety diseases including Parkinson’s disease and depression. Therefore, thestudy on resonance property and neurons mechanism of DA resonance of PDwill discover the PD pathogenesis from a new perspective. This research includetwo parts: in the first part we recorded the electrical activity of dopaminergicneurons with infrared visual whole-cell patch clamp in rat horizontal brain slices;in the second part we studied its resonant characteristic and ionic mechanisms.1.Membrane resonance of dopaminergic neurons in substantia nigracompacta.Oscillation is an important biological rhythm in the brain. Whether a singleneurons or the whole neural network, the oscillation is of great significance for the functions of the brain. Resonance is used to describe the frequency-selectiveability of neurons to respond the input signal, and is one of the internalmechanisms of oscillation. As one of these intrinsic neuronal properties, θresonance has been found in hippocampal CA1pyramidal neurons, horizontalinterneurones in the stratum oriens, and stellate cells from layer II of the medialentorhinal cortex. As the one of the main type neurons in the brain, thedopaminergic neurons have unique physiological significance and functions insubstantia nigra compacta structure, as well as its direct and indirect pathways inbrain network. However, there is no data to show that membrane resonanceexists in DA neurons of substantia nigra compacta. Therefore, the first step ofthe research is to give the sine current (ZAP,0Hz~16Hz,20s) stimulation, whichwas continuously changed by the increasing frequency over time, to DA neuronsof substantia nigra compactan. Then we calculated the membrane resonantfrequency of neurons, and discuss the properties of DAergic neuronsmembrane resonance.Main results:1). The electrophysiological activities of dopaminergic neurons were recordedby whole-cell patch clamp in substantia nigra compacta in horizontal slices. Theresults with TH staining showed that these neurons were fusiform neurons.2). According to the different firing patterns evoked by depolarizing currentstimulation, the DA neurons of SNc can be defined as regular spiking neurons.The experiment showed that all the DA neurons presentresonant response to theZAP stimulation in the range of-55mV and-85mV.3). Membrane resonance frequency of the DA neurons were temperaturedependent. In other words, the frequency would increase with the rising of thetemperature. The frequency was increased from2Hz to4Hz with the temperature changed from33℃to38℃.And the frequency was in θ frequencyrange.4). Membrane resonance of DA neurons was voltage dependent. In differentmembrane potential levels, it showed different frequency of resonance.2. The Ionic mechanism of membrane resonance for dopaminergic neuronsin substantia nigra compactaAs reported, the main ionic channels related to DA neurons are K+, Na+and Ca2+ionic channels. Ih current is a mixture current which involves K+, Na+and otherpositive ionic components. Several studies have confirmed its modulation role inthe research of the neuron membrane excitability and its rhythms activities inseveral regions of neurons system. The research shows that Ih current havedifferent ways of modulation to synaptic transmission in presynaptic andpostsynaptic neurons. In addition, it has been confirmed in hippocampal neuronsand cortex. As an active current, it has participated in and thus formedsubthreshold membrane resonance. However, it is not clear that whether itparticipates in the formation of subthreshold membrane resonance of DAneurons as an active current. Besides, whether other ion channels have alsoinvolved in or mediated the properties of the subthreshold membrane resonanceof DA neurons was still unclear. At present, researches have shown that theblocking and activating of the small-conductance calcium-dependent potassiumchannel have some effect on the pacing and excitability of the DA neurons. Butits functions on the properties of membrane resonance still need furtherresearch.Main results:1). Hyperpolarization-activated cation current is the active current component toproduce theta frequency membrane resonance in DA neurons. The current component takes effect in the range of-65to-85mV.2). The small-conductance calcium-dependent potassium channel is also theactive current component to produce theta frequency membrane resonance inDA neurons. It ranges from-60to70mV.3). Persistent sodium currents, INap could magnify the amplitude of themembrane resonance at the level of depolarized transmembrane potential.Main conclusions:1). Dopaminergic neurons in substantia nigra compacta is about-65mV, theactive current which can produce membrane resonance is SK channel current.2). Dopaminergic neurons in substantia nigra compacta is about-75mV, theactive current which can produce membrane resonance is h current.3). INapcan diminish the membrane resonance amplitude in the hyperpolarizedlevel, but it has no effect on resonance frequency.4).Calcium ions involved in membrane resonance, but the specificmechanisms need further study.Our study showed that the membrane resonance of dopamine neurons insubstantia nigra pars compacta belonged to the θ frequency. Its ionic mechanismhad some particularity feature. This unique ionic mechanisms was better tounderstand the membrane resonance of DA neurons in substantia nigra parscompacta and important roles in the network. By the way, it provide a basicstudy for PD patients in electrophysiological features.