| Neurological disorders are regarded as significant contributors to mortality and disability.Consequently,there is an urgent need for the development of effective neural modulation techniques for intervention and treatment of these associated conditions.Exploring the principles governing neural modulation techniques in shaping the morphology and functionality of neurons holds profound theoretical value and practical importance in advancing the field of neural modulation and the treatment of neurological diseases.Terahertz radiation stands as a non-invasive neural modulation technique,operating at the molecular level by exciting non-linear protein resonances to modulate neuronal morphology and function.Hence,terahertz radiation harbors immense potential for intervening and treating conditions related to neurodevelopmental disorders.However,the long-term regulatory patterns of terahertz radiation on the dynamic growth,development,and morphology of neurons remain unclear,as does the correlation between changes in neuronal morphology and kinetic properties following terahertz radiation.Additionally,the modulation mechanisms of terahertz radiation on neuronal synaptic transmission and plasticity require further elucidation.Thus,this dissertation undertakes relevant research addressing these issues,with specific research and innovative contributions outlined below:Firstly,in order to enable real-time monitoring of the response of neuronal morphology and functionality to different parameter terahertz radiation,we developed both broadband and narrowband terahertz radiation neuronal experimental platforms that are compatible with neuronal morphology recording and electrophysiological systems.Given the diversity of radiation samples,adjustments to the direction and beam size of terahertz radiation are typically necessary during the course of the research.Therefore,this study employed the refraction method of plano-convex lenses and the ABCD law of Gaussian beams to optimize the terahertz wave transmission path.By altering the number and relative distances of lenses,it became feasible to adjust the size of the radiation spot.Additionally,we conducted tests to determine the absorption characteristics of terahertz radiation by various samples,including culture media,cerebrospinal fluid,rat brain tissue slices,and skull specimens.Secondly,to elucidate the mechanisms underlying the interaction between terahertz waves and neurons,we established a model for the propagation and thermal effects of terahertz waves within neurons.We analyzed the dielectric properties of neurons in the terahertz frequency range.In the simulation process,we employed the finite element method to solve for the distribution of terahertz wave field intensity and temperature within neurons.Additionally,we investigated the influence of different terahertz radiation protocols(frequency,power,and exposure duration)and neuronal dimensions on the outcomes.Consequently,we proposed selection criteria and methods for radiation protocols based on the propagation characteristics of terahertz waves within neurons and their thermal effects.Thirdly,to uncover the regulatory patterns and long-term effects of terahertz radiation on the dynamic growth and development of neurons,a short-term cumulative terahertz radiation approach was proposed.In this dissertation,both broadband low-dose(0.3-3THz,maximum radiation power 100μW)and narrowband high-power(0.138 THz,maximum radiation power 2m W)terahertz radiation systems were used for short-term cumulative radiation(3 min/day,20 min/day,totaling 3 days)of neurons.Neuronal dynamic growth and morphological changes were continuously monitored in real-time.Neuronal soma area,total neurite length,and the soma-neurite membrane area ratio were employed as metrics for assessing neuronal growth and morphological changes.The study aimed to investigate the impact patterns and cumulative effects of broadband low-dose and narrowband high-power terahertz radiation on neuronal dynamic growth and development.Then,in order to elucidate the correlation between changes in neuronal morphology following terahertz radiation and neuronal functionality,a novel approach was introduced.This approach involved utilizing the ratio of neuronal soma area to neurite membrane area as a regulatory factor in the context of terahertz radiation,and constructing a terahertz radiation-modulated neuronal model.During the simulation process,the viability of the constructed model was verified,demonstrating its capability to replicate the firing characteristics of pyramidal neurons and assess the impact of morphology on these characteristics under terahertz radiation.Furthermore,the study involved an analysis of the relationship between alterations in neuronal morphology after broadband low-dose and narrowband high-power terahertz radiation and neuronal action potentials and postsynaptic currents,ultimately shedding light on the influence of terahertz radiation duration on neuronal firing properties.Finally,in order to reveal the law that terahertz radiation modulates neuronal synaptic transmission and synaptic plasticity,a research method using terahertz continuous radiation of hippocampal slices was proposed.In the study,real-time postsynaptic field potentials of the CA1 region of the hippocampus were acquired,and the changing law of the kinetic parameters of the postsynaptic potentials with the radiation time was analyzed.In addition,in order to further explore the regulatory mechanisms of terahertz radiation,the changing patterns of synapse-related proteins and dendritic spine density in neurons after terahertz radiation were analyzed using immunoblotting and Golgi staining techniques.In the data analysis,in order to be able to accurately and efficiently extract the kinetic parameters of neuronal postsynaptic potentials from the raw signals containing noise and stimulus artifacts,an algorithm based on adaptive singularity spectral analysis for the extraction of kinetic features of the postsynaptic potentials was proposed. |
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