WO2020107633A1 - 动物抓力测量方法及系统 - Google Patents

动物抓力测量方法及系统 Download PDF

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Publication number
WO2020107633A1
WO2020107633A1 PCT/CN2018/125631 CN2018125631W WO2020107633A1 WO 2020107633 A1 WO2020107633 A1 WO 2020107633A1 CN 2018125631 W CN2018125631 W CN 2018125631W WO 2020107633 A1 WO2020107633 A1 WO 2020107633A1
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grip
light
neurons
specific brain
subject
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French (fr)
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贾香连
王立平
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Shenzhen Institute of Advanced Technology of CAS
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Shenzhen Institute of Advanced Technology of CAS
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/22—Ergometry; Measuring muscular strength or the force of a muscular blow
    • A61B5/224—Measuring muscular strength

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  • the embodiments of the present application relate to the field of biomedical technology, for example, to an animal grip measurement method and system.
  • Grip is a kind of mechanical stress that the animal's limb (mainly forelimb) muscles are in a relaxed state. It can help maintain the state and position of the limbs between the joints, while providing the necessary pressure for the establishment of limb muscle movement. It is of great significance to use the experimental animal model to study the grip strength.
  • the grip strength can indirectly reflect the influence of the aging, nerve injury and muscle injury degree of the experimental animal model on muscle strength.
  • the grip strength measurement can only be used for the study of muscle tone after chronic stimulation.
  • the experimental animal needs to respond after receiving stimulation for a period of time.
  • the animal's nervous system controls muscle grip is an acute reaction.
  • the main disadvantage of the above technique is that it cannot be performed when the animal receives external stimuli. Real-time measurement.
  • the present application provides an animal grip measurement method and system, which can realize light stimulation to an experiment object and improve the real-time performance of grip measurement.
  • an embodiment of the present application provides an animal grip measurement method, including:
  • an embodiment of the present application provides an animal grip measurement system, including: a gene editing device, an optogenetic control device, and a grip measurement device;
  • the gene editing device controls the expression of the photosensitive protein of the test subject on neurons in a specific brain region through gene editing technology; the optogenetic control device irradiates the photosensitive protein with light of a preset wavelength to the specific brain region Neurons perform light stimulation; the grip force measuring device receives the grip force generated by the experimental object in real time after receiving the photo stimulation and calculates the grip force value.
  • FIG. 1 is a flowchart of a method for measuring animal grip provided by Embodiment 1 of the present application;
  • Embodiment 2 is a flowchart of a method for measuring animal grip provided by Embodiment 2 of the present application;
  • Example 3 is a schematic diagram of measuring the grip strength of an animal provided by Example 2 of the present application.
  • FIG. 4 is a schematic structural diagram of an animal grip measurement system provided in Embodiment 3 of the present application.
  • FIG. 5 is another schematic structural diagram of an animal grip strength measurement system provided in Embodiment 3 of the present application.
  • FIG. 1 is a flowchart of a method for measuring the grip strength of an animal provided in Embodiment 1 of the present application. This embodiment can be applied to the case of measuring the grip strength of rodents such as rats and mice.
  • the animal grip measurement method can be implemented in software and/or hardware, and integrated in the animal grip measurement system.
  • the animal grip measurement system includes: a gene editing device, an optogenetic regulation device, and a grip measurement device; the gene editing device controls the expression of the light-sensitive protein of a test subject on neurons in a specific brain region through gene editing technology; The optogenetic control device irradiates the photosensitized protein with light of a preset wavelength to perform photostimulation on neurons in the specific brain region; the grip measurement device receives in real time the experimental object generated after receiving the photostimulation Holding power and calculating the holding power value.
  • the method includes the following steps: S110-S130.
  • the light-sensitive protein of the test subject is controlled to be expressed on neurons in a specific brain region by gene editing technology.
  • the experimental objects in this embodiment mainly refer to rodents (rodents), which stimulate the neurons in specific brain regions of the animal by using light of a predetermined wavelength to cause the animal to respond to the stress Instinctively generate grip. Controlling the expression of light-sensitive proteins that can respond to external light stimuli on neurons in specific brain regions of the subject, this step is achieved by gene editing technology.
  • Genome editing refers to the "editing" of target genes to achieve the knockout, insertion and replacement of specific DNA fragments, such as CRISPR (clustered and regularly spaced short palindrome repeats, Clustered Regularly Interspaced Shorted) Palindromic Repeat)/Cas9 is a more advantageous gene editing technology, which is considered to be able to "edit” any gene more efficiently and more conveniently in living cells; the process of gene editing of experimental subjects can also be understood as The gene sequence that affects the expression of light-sensitive protein is inserted into a harmless virus, and then the required gene sequence is inserted into the genome of the neuron cell of the specific brain region of the test subject using the viral vector, so that the light-sensitive protein can be expressed in the nerve of the specific brain region Meta cells.
  • CRISPR Clustered Regularly Interspaced Shorted
  • Viral vectors can be used to directly select specific neuronal cells to express light-sensing genes.
  • the advantage of this method is that the preparation cycle is short.
  • the expression of the target gene is limited to the injection site, that is, neurons in specific brain regions, so it has better Spatial selectivity.
  • Photosensitive protein is a kind of protein that can produce physiological response in response to light signal in living body, and has important physiological significance for ion flow and cell signal transmission inside and outside neurons.
  • Gene editing technology is used to express photosensitizing proteins (ChR2 or eNpHR) on neurons in specific brain regions.
  • the specific brain regions mainly refer to the brain regions that control the limb movement and muscle tone of the subject.
  • the photosensitizing protein receives external light stimulation , It will promote the ion flow of neuron cells in this brain area to achieve the depolarization of neuron cells, thereby producing the effect of activating or inhibiting the activity of neuron cells.
  • Neurotransmitters continue to transmit this biological electrical signal to the next A neuron, which ultimately affects the subject’s limb muscles to produce grip.
  • the light-sensitive protein is irradiated with light of a preset wavelength to photostimulate neurons in the specific brain region.
  • the photosensitive protein mainly refers to the ion channel type photosensitive protein, including purpurin channel protein 2 (Channelrhodopsin-2, ChR2), eNpHR and variants, when ChR2 (and its variants) is expressed in the brain area that controls blood glucose metabolism After the neuron cell membrane is irradiated with predetermined wavelengths of light, ChR2 will open the ion channel of the cell membrane, causing K + outflow and Na + inflow, resulting in depolarization of the cell, thereby activating neurons, simulating the effects of nerve impulses. Neurons produce bioelectrical signals.
  • purpurin channel protein 2 Channelrhodopsin-2, ChR2
  • eNpHR purpurin channel protein 2
  • ChR2 will open the ion channel of the cell membrane, causing K + outflow and Na + inflow, resulting in depolarization of the cell, thereby activating neurons, simulating the effects of nerve impulses.
  • Neurons produce bioelectrical signals
  • eNpHR (and its variants) is expressed on the neuronal cell membrane of the brain region that controls movement and muscle tension
  • irradiating eNpHR with light of a preset wavelength can play a role in inhibiting the activity of neurons, which ultimately affects the experimental subject’s Holding power.
  • the use of light-sensitive protein to receive light stimulation to activate or inhibit neurons is basically harmless to cells, and can quickly play a role in generating grip for the test subjects.
  • Neuronal cells that do not express light-sensitive proteins do not respond to light stimulation.
  • the subject by placing the subject on a platform for measuring grip, the subject will instinctively grasp the rod-like or mesh-like objects provided by the platform after receiving light stimulation to generate grip, using a load cell It can receive grip force and calculate grip value in real time.
  • the grip force sensor converts the received grip force into an electrical signal proportional to the magnitude of the grip force, and the grip force can be calculated and displayed according to the voltage value of the electrical signal.
  • An animal grip measurement method provided in Example 1 of the present application expresses a photosensitive protein on a neuron cell in a specific brain region through gene editing technology, and then irradiates the photosensitive protein with light of a preset wavelength to light the neuron cell Stimulation, real-time receiving the grip force generated by the experimental object after receiving the optical stimulus and calculating the grip value, realizing photo stimulation of the experimental object and improving the real-time performance of the grip force measurement.
  • FIG. 2 is a flowchart of an animal grip measurement method provided in Embodiment 2 of the present application. This embodiment is optimized on the basis of the foregoing embodiments. For technical details that are not described in detail in this embodiment, refer to any of the above embodiments.
  • the method includes the following steps: S210-S280.
  • the light-sensitive protein of the test subject is controlled to be expressed on the neurons of the specific brain region through gene editing technology.
  • a modulation signal is generated according to a preset waveform, frequency, amplitude, and duty ratio.
  • a waveform generator can be used to generate a modulation signal with a certain waveform, frequency, amplitude, and duty cycle according to actual needs.
  • the modulation signal is used to adjust the light of a preset wavelength emitted by the light source.
  • the preset waveforms include square wave, sine wave and pulse wave, different waveforms will affect the period and time of photostimulation; the preset frequency determines the frequency of photostimulation of neurons; the preset amplitude determines the The intensity of the neuron's light stimulation; the preset duty cycle determines the mode of light stimulation of the neuron.
  • the light of the preset wavelength emitted by the light source is modulated according to the modulation signal.
  • the light source in this example is a laser
  • the modulated signals of the preset waveform, frequency, amplitude, and duty cycle generated by the waveform generator are input into the laser, and the laser is loaded with a specific electrical signal to output light.
  • the parameters of the laser oscillation can be changed according to the law of the modulation signal, that is, the formation of the laser can be controlled by using the modulation signal.
  • the laser is used to provide a light source with a preset wavelength.
  • the light of the preset wavelength emitted by the laser is modulated according to the modulation signal. According to different actual needs, the frequency, time, intensity, etc. of the light stimulation can be changed to achieve comprehensive light control. Stimulation parameters.
  • the light of the preset wavelength after being irradiated is used to irradiate the photosensitized protein to perform photostimulation on neurons in the specific brain region.
  • the irradiating the photosensitive protein with light of a preset wavelength to perform photostimulation on neurons in the specific brain region includes:
  • different wavelengths of light are used to activate or inhibit ion channel type photosensitive proteins expressed on the cell membrane of neurons, respectively, to regulate neuronal activity.
  • ChR2 and ChR2 variants are expressed on the neuronal cell membrane of the brain region that controls blood glucose metabolism, the blue ionization of the wavelength of 473nm can be used to open the ion channel, and the neuronal cells will secrete neurotransmitters to regulate or directly transmit this biological electrical signal.
  • eNpHR and variants of eNpHR are expressed on the neuronal cell membrane of the brain area that controls movement and muscle tone, and then use yellow light with a wavelength of 593nm to suppress these nerves. Meta-activity will ultimately affect the grip of the experiment subject.
  • the experimental subject is placed on the grasping net. After receiving the light stimulus, the experimental subject will react immediately and instinctively to generate grasping power.
  • the grasping net can be used to receive the grasping force of the experimental subject in real time.
  • the grip force is converted into an electrical signal.
  • the force sensor can be used to convert the received grip force into an electrical signal.
  • the grip sensor includes one or more elastic bodies that can deform after being stressed, and a bridge circuit (such as a Wheatstone bridge) composed of resistance strain gauges that can sense this deformation. After receiving the grip of the test subject, the strain gauge attached to the elastic body deforms and causes resistance changes. The resistance changes make the Wheatstone bridge out of balance and output an electrical signal that changes linearly in proportion to the external force. .
  • the grip value is calculated according to the voltage value of the electrical signal.
  • the voltage value is converted into a grip value according to a certain conversion rule, and the grip value is proportional to the voltage value to reflect the magnitude of the grip.
  • the grip value measured under the conditions of different waveforms, frequencies, amplitudes, duty cycles and preset wavelengths can be recorded to obtain different light stimulation time, frequency, intensity, light
  • the grip force generated when the neuron is activated or inhibited for comprehensive grip force measurement and data analysis can be recorded to obtain different light stimulation time, frequency, intensity, light
  • the use of light stimulation to activate or inhibit the activity of neurons has high time-resolved characteristics, so it can establish a good time-dependent relationship during data analysis, thereby improving the real-time performance of grip measurement.
  • the average value of the grip force value of the test subject is calculated through multiple measurements under the same set parameters, and the entire grip force measurement process is performed in a dark environment to avoid the influence of external light on the grip force measurement, Minimize measurement errors and improve the accuracy of measuring grip.
  • the infrared camera is used to monitor the entire grip measurement process. When an operation error occurs, the wrong value is eliminated to improve the authenticity of the data.
  • the instrument used in the experiment in this embodiment is connected to a PC, and the PC is used to read the relevant parameters of light stimulation and the corresponding grip value, which is convenient for comprehensive analysis and processing of the data .
  • FIG. 3 is a schematic diagram of measuring the grip strength of an animal provided in Embodiment 2 of the present application.
  • the photosensitive protein is expressed on neurons in specific brain regions.
  • the subject can respond to external light stimuli to generate grip.
  • the gene-edited experimental object 204 is subjected to light stimulation, and the waveform generator 201 is used to generate modulation signals of different waveforms, frequencies, amplitudes, and duty cycles.
  • the laser 202 is used to generate light of a preset wavelength.
  • the modulation signal generated by the waveform generator 201 is input to the laser 202 for modulation, and finally generates light with specific preset parameters, and the laser is introduced into the brain of the experimental subject 204 through the fiber jumper 203, and the photosensitive protein is irradiated to the specific brain area Neurons perform light stimulation, the subject 204 instinctively grasps the grasping net 205, and the force exerted by the subject 204 on the grasping grid is read and calculated by the grasping sensor 206 connected to the grid, and The measured grip force value is displayed on the display screen 207.
  • the grasping net 205, the grasping force sensor 206 and the display screen 207 can be provided by Reward grasping tester.
  • An animal grip measurement method provided in Example 2 of the present application is optimized on the basis of the above-mentioned embodiment, and activates or suppresses the experimental object by generating light with different waveforms, frequencies, amplitudes, and duty cycles at preset wavelengths.
  • Neurons in a specific brain area enable it to instantly generate grip power, improve the real-time performance of grip force measurement, and realize the adjustment of light source parameters to comprehensively measure grip power under different light stimulation modes.
  • FIG. 4 is a structural diagram of an animal grip measurement system 300 provided in Embodiment 3 of the present application.
  • the animal grip strength measurement system 300 provided by this embodiment includes: a gene editing device 310, an optogenetic regulation device 320, and a grip strength measurement device 320;
  • the gene editing device 310 controls the expression of the photosensitive protein of the test subject on neurons in a specific brain region through gene editing technology; the optogenetic control device 320 irradiates the photosensitive protein with light of a preset wavelength to the specific brain Neurons in the area perform light stimulation; the grip force measuring device 320 receives in real time the grip force generated by the subject after receiving the photo stimulation and calculates the grip force value.
  • the gene editing device 310 refers to a medical device that can use a viral vector to insert a desired gene sequence into the genome of a subject neuron, and can be provided by the CRISPR-Cas9 gene editing platform.
  • the photosensitive protein is expressed on neurons in specific brain regions.
  • the function of the optogenetic control device 320 is to generate a light source of a specific wavelength according to preset parameters after the gene editing device 310 completes gene editing and irradiates the photosensitive protein on the neuron cells of the specific brain region to provide photostimulation to the test subject.
  • the regulating device 320 can regulate the frequency, intensity, time, etc. of the light stimulation, so as to comprehensively measure and analyze the grip force generated by the experiment object in different stimulation modes.
  • the grip force measuring device 320 is used by the optogenetic control device 320 to perform light stimulation on the experimental object, and then receives the grip force of the experimental object in real time and converts it into a grip value.
  • An animal grip strength measuring device controls the expression of a photosensitive protein of a test subject on a neuron in a specific brain region through a gene editing device; the photosensitive device is irradiated with light of a preset wavelength by an optical genetic control device Protein, to stimulate the neurons in the specific brain area; the grip force measurement device receives the grip force generated by the experimental subject in real time after receiving the photo stimulation and calculates the grip value, so that the experimental subject is different
  • the mode of light stimulation improves the real-time performance of grip measurement.
  • FIG. 5 is another schematic structural diagram of an animal grip strength measurement system provided in Embodiment 3 of the present application.
  • the optogenetic control device 320 includes a waveform generator 321, a laser 322, an optical fiber jumper 323, and an optical fiber ferrule 324.
  • the modulation signal generated by the waveform generator 321 is input to the laser 322, and the laser 322 generates light of a preset wavelength according to the modulation signal, and the light of the preset wavelength is transmitted to the optical fiber through the fiber jumper 323
  • the optical fiber ferrule 324 is implanted in a specific brain area of the subject.
  • the waveform generator 321 can generate a preset modulation signal according to actual needs, and the modulation signal is used to adjust the light of the preset wavelength emitted by the laser 322.
  • the preset waveforms in the modulation signal include a square wave, a sine wave, and a pulse wave, which are used to affect the period and time of the light stimulation; the modulation signal generated by the waveform generator 321 is also used to affect the frequency of the light of the preset wavelength, Amplitude and duty cycle to control the frequency, intensity and pattern of light stimulation.
  • the laser 322 is used to generate light with a preset wavelength according to the modulation signal, including a blue laser and a yellow laser.
  • the blue laser is used to generate blue light with a wavelength of 473 nm to activate neurons expressing ChR2; the yellow laser is used to generate Yellow light with a wavelength of 593 nm to suppress neuronal cells expressing eNpHR. Regardless of whether it is blue light or yellow light, the waveform, frequency, amplitude, and duty ratio of the blue light or yellow light are changed according to the modulation signal generated by the waveform generator 321.
  • the fiber jumper 323 is used to export the light of the preset wavelength generated by the laser 322 and transmit it to the fiber ferrule 324.
  • the optical fiber ferrule 324 is embedded in a specific brain area of the test subject, and is used to introduce light into the specific brain area to irradiate the photosensitive protein, activate or inhibit the neuron activity of the specific brain area, and make the test subject produce grip.
  • the waveform generator 321 generates analog signals of waveforms with different waveforms, frequencies, amplitudes, and duty cycles and inputs them to the laser 322.
  • the modulation signal generated by the waveform generator 321 is used to determine the waveform, frequency, amplitude, and duty cycle of light of a preset wavelength to adjust the time, frequency, intensity, and light stimulation mode of the light stimulation.
  • the grip force measurement device 320 includes: a grip net 331, a grip sensor 332, and a display screen 333;
  • the grasping net 331 receives the grasping force generated by the subject after receiving the light stimulus in real time, the grasping force sensor 332 converts the grasping force into an electrical signal, and calculates the grasping force according to the voltage value of the electrical signal For the force value, the display screen 333 displays the grip force value.
  • the experiment subject is placed on the grasping net 331, and the experiment subject will react instinctively and instantaneously to generate grasping force after receiving the light stimulation.
  • the grasping net 331 can receive the grasping force of the experiment subject in real time.
  • the force sensor 332 can convert the received grip force into an electrical signal, which changes linearly in proportion to the grip force, and converts the voltage value of the electrical signal into the grip force value according to a certain conversion rule.
  • the display screen 333 is used to display the measured grip value in real time.
  • the number of grip sensors 332 in the grip measurement device 320 may be one or two. When there is only one grip sensor 332, it is used to measure the grip of the forelimb of the subject; the grip sensors 332 are two At this time, it can be used to test the grip of the forelimb and hindlimb of the test subjects respectively.
  • the animal grip measurement system 300 further includes a PC 340, which is connected to the grip measurement device 320 through a data line to read the relevant parameters of the light stimulation, that is, the corresponding grip values, to facilitate Analyze and process the above data.
  • a PC 340 which is connected to the grip measurement device 320 through a data line to read the relevant parameters of the light stimulation, that is, the corresponding grip values, to facilitate Analyze and process the above data.
  • the system further includes an infrared camera, which monitors the grip measurement process through the infrared camera.
  • the grip force measurement process is performed in a dark environment, and the infrared force camera monitors the grip force measurement process. When an operation error occurs, the wrong value is removed to improve the authenticity of the data.
  • the animal grip measurement device provided in Embodiment 3 of the present application can be used to perform the animal grip measurement method provided in any of the above embodiments, and has corresponding functions and beneficial effects.

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Abstract

一种动物抓力测量方法及系统，方法包括：通过基因编辑技术控制实验对象（204）的光敏蛋白表达在特定脑区的神经元上；使用预设波长的光照射光敏蛋白，对特定脑区的神经元进行光刺激；以及实时接收实验对象（204）在接收光刺激后产生的抓力并计算抓力值。

Description

动物抓力测量方法及系统
本申请要求在2018年11月29日提交中国专利局、申请号为201811444915.6的中国专利申请的优先权，该申请的全部内容通过引用结合在本申请中。
技术领域
本申请实施例涉及生物医学技术领域，例如涉及一种动物抓力测量方法及系统。
背景技术
抓力是动物的肢体(主要是前肢)肌肉处于松弛状态下所具有的一种机械应力，它能够帮助肢体保持在关节之间的状态和位置，同时为肢体肌肉运动的建立提供必要的压力。利用实验动物模型对抓力进行研究具有非常重要的意义，抓力能够间接反映实验动物模型的衰老、神经损伤以及肌肉损伤程度等对肌力的影响。
目前，已经有多种测试动物抓力的仪器，但由于刺激条件的限制，抓力的测量只能用于慢性刺激后肌肉张力的研究，例如，对实验动物实施药物、毒理等刺激后再进行抓力测量，实验动物需要在接收刺激一段时间后才能做出反应，然而，动物的神经系统控制肌肉抓力是一种急性反应，上述技术的主要缺点是不能在动物接收到外界刺激时进行实时测量。
发明内容
本申请提供了一种动物抓力测量方法及系统，可以实现对实验对象进行光刺激，提高抓力测量的实时性。
第一方面，本申请实施例提供了一种动物抓力测量方法，包括：
通过基因编辑技术控制实验对象的光敏蛋白表达在特定脑区的神经元上；
使用预设波长的光照射所述光敏蛋白，对所述特定脑区的神经元进行光刺激；以及
实时接收所述实验对象在接收所述光刺激后产生的抓力并计算抓力值。
第二方面，本申请实施例提供了一种动物抓力测量系统，包括：基因编辑设备、光遗传调控装置以及抓力测量装置；
所述基因编辑设备通过基因编辑技术控制实验对象的光敏蛋白表达在特定脑区的神经元上；所述光遗传调控装置使用预设波长的光照射所述光敏蛋白，对所述特定脑区的神经元进行光刺激；所述抓力测量装置实时接收所述实验对象在接收所述光刺激后产生的抓力并计算抓力值。
附图说明
图1为本申请实施例一提供的一种动物抓力测量方法的流程图；
图2为本申请实施例二提供的一种动物抓力测量方法的流程图；
图3为本申请实施例二提供的对动物抓力进行测量的示意图；
图4为本申请实施例三提供的一种动物抓力测量系统的结构示意图；
图5为本申请实施例三提供的一种动物抓力测量系统的另一结构示意图。
具体实施方式
实施例一
图1为本申请实施例一提供的一种动物抓力测量方法的流程图，本实施例可适用于对大、小鼠等啮齿类动物的抓力进行测量的情况。在一实施例中，该动物抓力测量方法方法可以通过软件和/或硬件的方式实现，并集成在动物抓力测量系统中。其中，动物抓力测量系统包括：基因编辑设备、光遗传调控装置以及抓力测量装置；所述基因编辑设备通过基因编辑技术控制实验对象的光敏蛋白表达在特定脑区的神经元上；所述光遗传调控装置使用预设波长的光照射所述光敏蛋白，对所述特定脑区的神经元进行光刺激；所述抓力测量装置实时 接收所述实验对象在接收所述光刺激后产生的抓力并计算抓力值。
参考图1，该方法包括如下步骤：S110-S130。
S110中，通过基因编辑技术控制实验对象的光敏蛋白表达在特定脑区的神经元上。
在一实施例中，本实施例中的实验对象主要是指啮齿类(鼠类)动物，通过利用预设波长的光刺激该动物特定脑区的神经元，使该动物做出应激反应而本能地产生抓力。控制能够应答外界光刺激的光敏蛋白表达在实验对象特定脑区的神经元上，这一步骤通过基因编辑技术实现。基因编辑(Genome Editing)是指通过对目标基因进行“编辑”，实现对特定DNA片段的敲除、插入以及替换等，例如CRISPR(成簇而规律间隔的短回文重复序列，Clustered Regularly Interspaced Short Palindromic Repeat)/Cas9，是较具有优势的一种基因编辑技术，被认为能够在活细胞中较有效、较便捷地“编辑”任何基因；对实验对象进行基因编辑的过程也可以理解为，将影响光敏蛋白表达的基因序列插入到无害的病毒中，然后利用病毒载体将需要的基因序列插入到实验对象特定脑区神经元细胞的基因组中，以使光敏蛋白能够表达在特定脑区的神经元细胞上。通过病毒载体可直接选择特定的神经元细胞表达光感基因，此方法的优势是制备周期短，目的基因的表达只局限于注射位点，即特定脑区的神经元细胞，因此具有较好的空间选择性。
光敏蛋白是一类在生命体内能够应答光信号而产生生理学反应的蛋白，对于神经元细胞内外的离子流动及细胞信号传递有重要的生理意义。通过基因编辑技术使光敏蛋白(ChR2或eNpHR)表达在特定脑区的神经元上，特定脑区主要指控制实验对象肢体运动和肌肉张力的脑部区域，当光敏蛋白接收到外接的光刺激后，会促使此脑区内的神经元细胞的离子流动，实现神经元细胞的去极化，从而产生激活或抑制神经元细胞的活动的效果，神经递质将这种生物电信号继续传递到下一个神经元，最终影响实验对象的肢体肌肉产生抓力。
S120中，使用预设波长的光照射所述光敏蛋白，对所述特定脑区的神经元 进行光刺激。
在一实施例中，光敏蛋白主要指离子通道型光敏蛋白，包括紫红质通道蛋白2(Channelrhodopsin-2，ChR2)、eNpHR及变体，当ChR2(及其变体)表达在控制血糖代谢脑区的神经元细胞膜上后，利用预设波长的光照射ChR2，会打开细胞膜的离子通道，使得K +外流，Na +内流，造成细胞去极化，从而激活神经元，模拟神经冲动的影响导致神经元产生生物电信号。同理，eNpHR(及其变体)表达在控制运动、肌肉张力脑区的神经元细胞膜上后，利用预设波长的光照射eNpHR，可以起到抑制神经元活动的作用，最终影响实验对象的抓力。利用光敏蛋白接收光刺激以激活或抑制神经元，对细胞基本无害，可快速地发挥作用使实验对象产生抓力。不表达光敏感蛋白的神经元细胞对光刺激没有反应。
S130中，实时接收所述实验对象在接收所述光刺激后产生的抓力并计算抓力值。
在一实施例中，通过将实验对象放置在测量抓力的平台上，实验对象接收光刺激后会本能地抓住平台所提供的杆状或网状等物体，产生抓力，利用测力传感器可实时接收抓力并计算抓力值。示例性的，通过抓力传感器将接收到的抓力转换为与抓力大小成正比的电信号，根据电信号的电压值可计算抓力并进行显示。
本申请实施例一提供的一种动物抓力测量方法，通过基因编辑技术将光敏蛋白表达在特定脑区的神经元细胞上，然后利用预设波长的光照射光敏蛋白，对神经元细胞进行光刺激，实时接收所述实验对象在接收所述光刺激后产生的抓力并计算抓力值，实现了对实验对象进行光刺激，提高抓力测量的实时性。
实施例二
图2为本申请实施例二提供的一种动物抓力测量方法的流程图，本实施例是在上述实施例的基础上，进行优化。未在本实施例中详尽描述的技术细节可参见上述任意实施例。
在一实施例中，参考图2，该方法包括如下步骤：S210-S280。
S210中，通过基因编辑技术控制实验对象的光敏蛋白表达在特定脑区的神经元上。
S220中，根据预设的波形、频率、幅度和占空比产生调制信号。
在一实施例中，利用波形发生器可根据实际需求产生一定波形、频率、幅度和占空比的调制信号，该调制信号用于对光源发出的预设波长的光进行调控。其中，预设的波形包括方波，正弦波和脉冲波，不同的波形会影响光刺激的周期和时间；预设的频率决定了对神经元进行光刺激的频率；预设的幅度决定了对神经元进行光刺激的强弱；预设的占空比决定了对神经元进行光刺激的模式。
S230中，根据所述调制信号对光源发出的预设波长的光进行调制。
在一实施例中，本实例中的光源为激光器，将波形发生器产生的预设波形、频率、幅度和占空比的调制信号输入激光器，通过为激光器加载特定的电信号以对输出的光进行调制。在激光形成过程中，按照调制信号的规律可以改变激光振荡的参数，即利用调制信号可控制激光的形成。激光器用于提供预设波长的光源，根据调制信号对激光器发出的预设波长的光进行调制，根据不同的实际需求，可改变光刺激的频率、时间以及强弱等，以实现全面地调控光刺激的参数。
S240中，使用调制后的预设波长的光照射所述光敏蛋白，对所述特定脑区的神经元进行光刺激。
在一实施例中，所述使用预设波长的光照射所述光敏蛋白，对所述特定脑区的神经元进行光刺激，包括：
将波长为473nm的蓝光导入所述实验对象的特定脑区，照射所述光敏蛋白，激活所述神经元；
或将波长为593nm的黄光导入所述实验对象的特定脑区，照射所述光敏蛋白，抑制所述神经元。
在一实施例中，分别利用不同波长的光激活或抑制表达在神经元细胞膜上 的离子通道型光敏蛋白，以调控神经元活动。ChR2及ChR2的变体表达在控制血糖代谢脑区神经元细胞膜上后，利用波长473nm的蓝光照射，可以打开离子通道，神经元细胞会分泌神经递质去调控或者将这种生物电信号直接传输给下一级神经元，最终将信息传输到控制抓力的肌肉；eNpHR及eNpHR的变体表达在控制运动、肌肉张力的脑区神经元细胞膜上后，利用波长593nm的黄光去抑制这些神经元活动，最终影响实验对象的抓力。
S250中，实时接收所述实验对象在接收所述光刺激后产生的抓力。
在一实施例中，将实验对象放置在抓网上，实验对象在接收光刺激后会即时、本能地做出反应产生抓力，利用抓网可实时接收实验对象的抓力。
S260中，将所述抓力转换为电信号。
在一实施例中，利用测力传感器可将接收到的抓力转换为电信号。示例性的，抓力传感器中包括了一个或多个能在受力后产生形变的弹性体，以及能感应这个形变量的电阻应变片组成的电桥电路(如惠斯登电桥)，在接收到实验对象的抓力作用后，粘贴在弹性体的应变片随之产生形变引起电阻变化，该电阻变化使组成的惠斯登电桥失去平衡输出一个与外力成线性正比变化的电量电信号。
S270中，根据所述电信号的电压值计算抓力值。
在一实施例中，根据一定的换算规则将电压值转换为抓力值，抓力值与电压值成正比，以反映抓力的大小。
S280中，记录所述波形、频率、幅度、占空比、预设波长和抓力值的对应关系。
在一实施例中，记录在不同波形、频率、幅度、占空比以及预设波长的情况下测量得到的抓力值，即可获得实验对象在不同的光刺激时间、频率、强弱、光刺激模式下，神经元被激活或抑制时产生的抓力，以进行全面的抓力测量和数据分析。利用光刺激来激活或者抑制神经元的活性，具有高时间分辨特性，因此在数据分析时能够建立良好的时间依赖(time-dependent)关系，从而提 高抓力测量实时性。
在一实施例中，在同一设定参数下通过多次测量计算实验对象抓力值的平均值，并且整个抓力测量过程在黑暗的环境中进行，以避免外界光线对抓力测量的影响，最大限度地减少测量误差，提高测量抓力的准确性。此外，利用红外摄像头监控整个抓力测量过程，当出现操作上的错误时，剔除错值，以提高数据的真实性。在一实施例中，通过将本实施例中实验过程中所采用的仪器与PC机连接，利用PC机读取光刺激的相关参数及对应的抓力值，便于对数据进行全面的分析和处理。
在上述实施例的基础上，图3为本申请实施例二提供的对动物抓力进行测量的示意图。在经过基因编辑后，光敏蛋白表达在特定脑区的神经元细胞上，此时，实验对象可以对外界的光刺激进行应答以产生抓力。如图3所示，对基因编辑后的实验对象204进行光刺激，利用波形发生器201产生不同波形、频率、幅度以及占空比的调制信号，激光器202用于产生预设波长的光，将波形发生器201产生的调制信号输入至激光器202中进行调制，最终产生具有特定的预设参数的光，通过光纤跳线203将激光导入到实验对象204的脑内，照射光敏蛋白对特定脑区的神经元实施光刺激，实验对象204会本能地抓住抓网205，实验对象204在抓网网格上施加的力度由连接在网格上的抓力传感器206来读取和计算，并在显示屏207中显示测得的抓力值。在抓力测量的过程中，将实验对象204放在网状平台上，拉住实验对象204的尾部，借助啮齿类动物自我保护的天性(前肢抓网)，利用抓力传感器206计算出前肢抓力的大小。其中，抓网205、抓力传感器206以及显示屏207可由瑞沃德抓力测试仪器提供。
本申请实施例二提供的一种动物抓力测量方法，在上述实施例的基础上进行优化，通过产生不同波形、频率、幅度和占空比的预设波长的光，激活或抑制实验对象的特定脑区的神经元，使其即时产生抓力，提高抓力测量的实时性，并且实现了对光源参数进行调控，在不同的光刺激模式下全面地测量抓力。
实施例三
图4为本申请实施例三提供的一种动物抓力测量系统300的结构图。参考图4，本实施例提供的动物抓力测量系统300包括：基因编辑设备310、光遗传调控装置320以及抓力测量装置320；
所述基因编辑设备310通过基因编辑技术控制实验对象的光敏蛋白表达在特定脑区的神经元上；所述光遗传调控装置320使用预设波长的光照射所述光敏蛋白，对所述特定脑区的神经元进行光刺激；所述抓力测量装置320实时接收所述实验对象在接收所述光刺激后产生的抓力并计算抓力值。
在一实施例中，基因编辑设备310是指能够利用病毒载体将需要的基因序列插入到实验对象神经细胞元的基因组中的医学设备，可以由CRISPR-Cas9基因编辑平台提供，通过基因编辑技术能够使光敏蛋白表达在特定脑区的神经元细胞上。光遗传调控装置320的功能是在基因编辑设备310完成基因编辑之后，根据预设参数产生特定波长的光源并照射特定脑区神经元细胞上的光敏蛋白，以对实验对象提供光刺激，光遗传调控装置320可以调控光刺激的频率、强度、时间等，以对实验对象在不同的刺激模式下产生的抓力进行全面的测量和分析。抓力测量装置320用于光遗传调控装置320对实验对象进行光刺激后，实时接收实验对象的抓力并将其转换为抓力值。
本申请实施例三提供的一种动物抓力测量装置，通过基因编辑设备控制实验对象的光敏蛋白表达在特定脑区的神经元上；通过光遗传调控装置使用预设波长的光照射所述光敏蛋白，对所述特定脑区的神经元进行光刺激；通过抓力测量装置实时接收所述实验对象在接收所述光刺激后产生的抓力并计算抓力值，实现了对实验对象进行不同模式的光刺激，提高抓力测量的实时性。
图5为本申请实施例三提供的一种动物抓力测量系统的另一结构示意图。在上述实施例的基础上，所述光遗传调控装置320，包括：波形发生器321、激光器322、光纤跳线323和光纤插芯324。
所述波形发生器321产生的调制信号输入至所述激光器322，所述激光器 322根据所述调制信号产生预设波长的光，所述预设波长的光通过所述光纤跳线323传输至所述光纤插芯324，所述光纤插芯324植入在所述实验对象的特定脑区。
在一实施例中，波形发生器321可根据实际需求产生预设的调制信号，该调制信号用于对激光器322发出的预设波长的光进行调控。其中，调制信号中预设的波形包括方波，正弦波和脉冲波，用以影响光刺激的周期和时间；波形发生器321产生的调制信号，还用于影响预设波长的光的频率、幅度及占空比，以调控光刺激的频率、强弱和光刺激模式。
激光器322用于根据所述调制信号产生预设波长的光，包括蓝光激光器和黄光激光器，蓝光激光器用于产生波长为473nm的蓝光，以激活表达ChR2的神经元细胞；黄光激光器用于产生波长为593nm的黄光，以抑制表达eNpHR的神经元细胞。无论是蓝光还是黄光，该蓝光或黄光的波形、频率、幅度以及占空比都是按照波形发生器321产生的调制信号变化的。
光纤跳线323用于将激光器322产生的预设波长的光导出，并传输至光纤插芯324。
光纤插芯324埋置在实验对象的特定脑区，用于将光导入特定脑区照射光敏蛋白，激活或者抑制特定脑区的神经元活动，使实验对象产生抓力。
在一实施例中，所述波形发生器321产生不同波形、频率、幅度和占空比的波形的模拟信号并输入至所述激光器322。
在一实施例中，波形发生器321产生的调制信号，用于决定预设波长的光的波形、频率、幅度和占空比，以调控光刺激的时间、频率、强弱以及光刺激模式。
在上述实施例的基础上，所述抓力测量装置320包括：抓网331、抓力传感器332和显示屏333；
所述抓网331实时接收所述实验对象在接收所述光刺激后产生的抓力，所述抓力传感器332将所述抓力转换为电信号，并根据所述电信号的电压值计算 抓力值，所述显示屏333显示所述抓力值。在一实施例中，将实验对象放置在抓网331上，实验对象在接收光刺激后会即时、本能地做出反应产生抓力，利用抓网331可实时接收实验对象的抓力，利用抓力传感器332可将接收到的抓力转换为电信号，该电信号与抓力成线性正比变化，根据一定的换算规则将电信号的电压值转换为抓力值。显示屏333用于实时显示测得的抓力值。
在一实施例中，抓力测量装置320中的抓力传感器332的数量可以为一个或两个，抓力传感器332只有一个时，用于测量实验对象前肢的抓力；抓力传感器332为两个时，可分别用于测试实验对象前肢和后肢的抓力。
在一实施例中，所述动物抓力测量系统300还包括PC机340，PC机340与抓力测量装置320通过数据线相连，以读取光刺激的相关参数即对应的抓力值，便于对上述数据进行分析和处理。
在一实施例中，所述系统还包括红外摄像头，通过红外摄像头对抓力测量过程进行监控。在一实施例中，抓力测量过程在黑暗的环境中进行，通过红外摄像头对抓力测量过程监控，当出现操作上的错误，剔除错值，以提高数据的真实性。
本申请实施例三提供的动物抓力测量装置可以用于执行上述任意实施例提供的动物抓力测量方法，具备相应的功能和有益效果。

Claims (10)

  1. 一种动物抓力测量方法，包括：
    通过基因编辑技术控制实验对象的光敏蛋白表达在特定脑区的神经元上；
    使用预设波长的光照射所述光敏蛋白，对所述特定脑区的神经元进行光刺激；以及
    实时接收所述实验对象在接收所述光刺激后产生的抓力并计算抓力值。
  2. 根据权利要求1所述的方法，其中，所述使用预设波长的光照射所述光敏蛋白，对所述特定脑区的神经元进行光刺激，包括：
    根据预设的波形、频率、幅度和占空比产生调制信号；
    根据所述调制信号对光源发出的预设波长的光进行调制；以及
    使用调制后的预设波长的光照射所述光敏蛋白，对所述特定脑区的神经元进行光刺激。
  3. 根据权利要求1所述的方法，其中，所述使用预设波长的光照射所述光敏蛋白，对所述特定脑区的神经元进行光刺激，包括：
    将波长为473nm的蓝光导入所述实验对象的特定脑区，照射所述光敏蛋白，激活所述神经元；或
    将波长为593nm的黄光导入所述实验对象的特定脑区，照射所述光敏蛋白，抑制所述神经元。
  4. 根据权利要求1所述的方法，其中，所述实时接收所述实验对象在接收所述光刺激后产生的抓力并计算抓力值，包括：
    实时接收所述实验对象在接收所述光刺激后产生的抓力；
    将所述抓力转换为电信号；以及
    根据所述电信号的电压值计算抓力值。
  5. 根据权利要求2所述的方法，还包括：
    记录所述波形、频率、幅度、占空比、预设波长和抓力值的对应关系。
  6. 一种动物抓力测量系统，包括：基因编辑设备、光遗传调控装置以及抓力测量装置；
    其中，所述基因编辑设备设置为通过基因编辑技术控制实验对象的光敏蛋白表达在特定脑区的神经元上；所述光遗传调控装置设置为使用预设波长的光照射所述光敏蛋白，对所述特定脑区的神经元进行光刺激；所述抓力测量装置设置为实时接收所述实验对象在接收所述光刺激后产生的抓力并计算抓力值。
  7. 根据权利要求6所述的系统，其中，所述光遗传调控装置，包括：波形发生器、激光器、光纤跳线和光纤插芯；
    其中，所述波形发生器设置为将产生的调制信号输入至所述激光器，所述激光器设置为根据所述调制信号产生预设波长的光，所述光纤跳线设置为传输所述预设波长的光至所述光纤插芯，所述光纤插芯设置为植入在所述实验对象的特定脑区。
  8. 根据权利要求7所述的系统，其中，所述波形发生器设置为产生不同波形、频率、幅度和占空比的调制信号并输入至所述激光器。
  9. 根据权利要求6所述的系统，其中，所述抓力测量装置包括：抓网、抓力传感器和显示屏；
    其中，所述抓网设置为实时接收所述实验对象在接收所述光刺激后产生的抓力，所述抓力传感器设置为将所述抓力转换为电信号，并根据所述电信号的电压值计算抓力值，所述显示屏设置为显示所述抓力值。
  10. 根据权利要求6所述的系统，还包括：红外摄像头；
    所述红外摄像头设置为对抓力测量过程进行监控。
PCT/CN2018/125631 2018-11-29 2018-12-29 动物抓力测量方法及系统 Ceased WO2020107633A1 (zh)

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AU2020302837A1 (en) * 2019-06-26 2022-01-27 The Bionics Institute Of Australia Combined light and electrical stimulation of light-sensitive neural tissue
CN112842604B (zh) * 2019-11-27 2022-12-06 香港理工大学深圳研究院 一种光遗传学实验方法与系统
CN114668409A (zh) * 2022-03-11 2022-06-28 北京工业大学 基于光遗传调控的人体神经接口系统及方法

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102106722A (zh) * 2011-02-28 2011-06-29 华中科技大学 一种光基因气味仿真系统
CN102283137A (zh) * 2011-08-25 2011-12-21 中国科学院深圳先进技术研究院 光遗传学调控的动物行为学测试平台
CN104523232A (zh) * 2014-12-26 2015-04-22 中国科学院深圳先进技术研究院 一种小型动物恐惧行为检测系统
WO2017049249A1 (en) * 2015-09-18 2017-03-23 Cheldren's Medical Center Corporation Devices and methods for analyzing animal behavior
CN108577870A (zh) * 2018-04-27 2018-09-28 中国科学院昆明动物研究所 一种实验猴上肢拉力测试装置

Family Cites Families (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20120010531A1 (en) * 2010-07-07 2012-01-12 University Of Maryland, Baltimore Small-Animal Unit for Muscle Injury, Muscle Testing and Muscle Training in Vivo
CN102649004B (zh) * 2011-02-25 2016-12-21 鸿富锦精密工业（深圳）有限公司 光照治疗仪
JP2014061084A (ja) * 2012-09-20 2014-04-10 Panasonic Corp 筋力推定装置
CN103638604B (zh) * 2012-12-31 2016-05-04 深圳先进技术研究院 一种助行系统
CN106377520B (zh) * 2016-08-16 2019-02-12 南方科技大学 神经保护剂
CN106725399A (zh) * 2016-12-29 2017-05-31 深圳先进技术研究院 一种光调控动物血压实时监测系统
CN206413574U (zh) * 2017-01-18 2017-08-18 苏州大学 一种小鼠行为学测试工具
CN107347707B (zh) * 2017-07-26 2022-11-11 上海中医药大学 一种大鼠静力性训练力学数据采集系统及测试方法

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102106722A (zh) * 2011-02-28 2011-06-29 华中科技大学 一种光基因气味仿真系统
CN102283137A (zh) * 2011-08-25 2011-12-21 中国科学院深圳先进技术研究院 光遗传学调控的动物行为学测试平台
CN104523232A (zh) * 2014-12-26 2015-04-22 中国科学院深圳先进技术研究院 一种小型动物恐惧行为检测系统
WO2017049249A1 (en) * 2015-09-18 2017-03-23 Cheldren's Medical Center Corporation Devices and methods for analyzing animal behavior
CN108577870A (zh) * 2018-04-27 2018-09-28 中国科学院昆明动物研究所 一种实验猴上肢拉力测试装置

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
LIANG TANG ET AL: "Construction of Gene Vaccine of Myostatin Fusion with T-helper Epitope and Its Effects on Forelimb Grip in Immunized Mice", CHINESE JOURNAL OF APPLIED PHYSIOLOGY, vol. 1, no. 29, 1 January 2013 (2013-01-01), pages 16 - 19, XP009521374, DOI: 10.13459/j.cnki.cjap.2013.01.012 *

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