The Modulation Of Central Pathway Nerve Conduction With Short-wavelength Near-infrared Laser Irradiation

Neuromodulation is an efficient technique to study how the neural activities operate brain functions,and it is also an important engineering technique to understand brain function and intervene brain disease.The conventional methods include mechanical stimulation,electrical stimulation,magnetic stimulation and optical stimulation etc,which present their own advantages and weaknesses respectively.Importantly,developing minimally invasive modulation techniques with high spatial-temporal resolution is an inevitable and beneficial trend.Near-infrared(NIR)laser has been extensively employed in modulating neuronal activity with its superiorities in non-contact and controlled stimulation range..Previous studies have demonstrated that NIR could not only activate induce neural response directly by changing the temperature field around the neural tissue through the thermal response of laser irradiated tissues,but also reversibly inhibit neuronal activity and block neural signal transduction with high spatial selectivity.Recently,the NIR research of neural regulation mainly focuses on the peripheral nervous system,neurons cultured in vitro and the superficial layer of the central nervous system,and the neuronal responsein the affected range of NIR Network connections and neural signal transduction exist between neurons and nerve nuclei.However,it is not clear about how the neuronal response and changes in functional state of central neurons modulated by NIR indectly affect other neurons and nerve nuclei by nerve pathways.Moreover,it is still a problem whether neuronal response evoked by NIR can transmit to other nerve nuclei through their own special pathway.Under the support of National Natural Science Foundation(NSFC31271060,31872751),impacts of SW-NIR on regulating central neural pathway nerve conduction has been thoroughly explored in this thesis;The auditory pathway with special frequency topological structure was selected to explore the feasibility of SW-NIR regulating auditory central pathway nerve conduction,meanwhile,SW-NIR was applied to the deep central nerve pathway to explore the feasibility of using SW-NIR in transcutaneous regulating the hippocampal pathway nerve conduction,so as to provides a new idea for the transmission regulation of neural pathways by SW-NIR.The following works have been carried on in this thesis:(1)In order to explore the inhibitory effect of SW-NIR on auditory central pathway nerve conduction,a temperature field model of laser irradiating the cochlear nuclear(CN)tissue was firstly established based on the COMSOL simulation software,and the effects of different light stimulation parameters on monitoring the tissue temperature were simulated considering the real size of CN,the boundary conditions of different tissue layers and the particularity of frequency topology in auditory pathway.The change of tissue temperature caused by different stimulus parameters was measured by near-infrared thermometry,and the model results were corrected according to the measured temperature.Based on the stimulation and measurement results,animal experiments were performed to observe the inhibitory effect of SW-NIR(980 nm)on the auditory center pathway nerve conduction.While the auditory pathway was activated by pure-tones through the rat's external auditory canal,SW-NIR was implemented on the rat's CN.The neural responses were recorded in the inferior colliculus(IC)by a multichannel electrode array(16 channels).The firing rates(FR)of IC neurons and the first spike latency(FSL)were then analyzed,and the state of neuronal tissue after light stimulation was tested.The result demonstrated that the 980 nm SW-NIR could effectively elevate the tissue temperature of CN to reversibly inhibit neuronal activity evoked by acoustical stimuli,block the transmission of neural signals to the neuronal tissue at the higher level of the CNS,and thus indirectly suppress IC neurons.The tissue temperature raised along with the increase of the stimulation magnitude,pulse width,and the distance from the fiber tip to the cerebrospinal fluid.Additionally,the different distance from the laser to the neuronal tissue with the optimal response could change the surface temperature of the neuronal tissue and then result in different inhibitory rate of IC neurons.The state analysis implied that the laser stimulation was not able to result in irreversible damages to the tissue.(2)Aiming to explore temporal characteristics of SW-NIR in inhibiting auditory pathway nerve conduction,four different stimulation paradigms were designed to investigate the temporal characteristics of the auditory pathway nerve conduction inhibited by SW-NIR according to the features of the time-varying curve of the temperature field induced by laser stimulation.And then animal experiments were performed to investigate the temporal characteristics of SW-NIR in inhibiting auditory pathway nerve conduction.The results revealed that different stimulus paradigms could induce the time changes of temperature field establishment,and then present variable effect on inhibition rate and FSL of IC neurons.Comparing with the sound and light synchronous stimuli(marked ed as: SS)paradigm,the light stimulation followed by sound stimulation(interval 5ms)(marked as DS-OA-5ms)paradigm resulted in higher inhibition rate and greater FSL variation.For SS paradigm,the tissue temperature and the changes of FSL increased with the increase of stimulation powers.In addition,different types of neurons also have distinct responses against the stimulation paradigms.It was demonstrated that the inhibition of SW-NIR on auditory central pathway depended on the establishment time of tissue temperature field.(3)For the activation of auditory central pathway by SW-NIR mediated by the gold nanorods,this thesis utilized the gold nanorods to mediate NIR to activate neurons.The temperature distribution of CN tissues induced by SW-NIR before and after the addition of gold nanorods was firstly simulated and measurement based on the temperature field model of CN irradiated by laser in chapter 3 and near-infrared temperature measurement technology.The simulation and measurement result before the addition of gold nanorods,the increased tissue temperature was mainly induced by heat transfer from the hydrocephalus layer to the tissue layer,while after adding gold nanorods,the extra effect on the increased tissue temperature resulted from tissue absorption of laser energy.As the increasing time after the addition of it,the concentration of gold nanorods decreases and then the increased tissue temperature also reduces.The veracity of the simulation is verified by near-infrared temperature measurement.And then,animal experiments were carried out to explore the activation of SW-NIR on auditory central pathway before and after the addition of gold nanorods.The results revealed that w the help of gold nanorods,SW-NIR could effectively and spatially selectively activate CN neurons to induce auditory response of auditory pathway and increase the response of induced neurons with the increase of stimulation magnitude.(4)To investigate transcutaneous modulation of deep hippocampus pathway by SW-NIR,we selected a part of the hippocampal excitatory "trisynaptic circuit" was selected as the research object.Laser stimulation was performed in hippocampus CA3 region,and the responses of hippocampal CA1 neurons were recorded by using16-channel electrode array.The results revealed that SW-NIR with a wavelength of 980 nm could securely and efficiently regulate nerve conduction in the deep hippocampus,that was,by directly regulating the neuronal release in CA3 region,it indirectly impacted the neuronal release in the CA1 region,presenting three different response types,namely,non-response,excitative response and inhibitory response.Under the experimental parameters of this study,with the increase of the stimulation magnitude,the number of neuron responses after the stimulus depicted a significant trend of increase,and more of them showed excitatory response.The effectiveness of SW-NIR in regulating central neural pathways was verified by theoretical simulation and animal experiments in this thesis.Based on the above results,the precise and transmissive regulation of SW-NIR may provide a new therapeutic perspective for designing treatments against tinnitus,epilepsy,Alzheimer's disease and other neurological disorders.