CN102283137A - Animal behaviour testing platform for optogenetics regulation and control - Google Patents
Animal behaviour testing platform for optogenetics regulation and control Download PDFInfo
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Abstract
The invention relates to an animal behaviour testing platform for optogenetics regulation and control, used for carrying out a behaviour test on tested animals. The testing platform comprises a central control system, an environmental control system, a behaviour monitoring system, a photoelectric detection, regulation and control system and a case device used for fixing the systems. A standard and integrated behaviour testing platform used for testing animal optogenetics regulation and control is established by combining an optogenetics neural regulation and control technology and electrophysiology and behaviour tests and the like; by virtue of the platform, optogenetics regulation and control as well as behaviour record on the tested animals in certain environment can be realized, thus being easy to understand relation between the animal optogenetics regulation and control and the behaviour and meeting requirements of research on pathogenesis and treatment mechanism of a nervous system and mental diseases.
Description
[technical field]
The present invention relates to medical instruments field, relate in particular to a kind of Animal Behavior Science test platform of smooth genetics regulation and control.
[background technology]
Central nervous system disease and mental illness are the principal diseases that threatens human health, the human normal life of puzzlement always.Central nervous system disease and mental illness whole world patient has exceeded 5.6 hundred million people at present, and wherein China just has 1.3 hundred million.For many years, people are studying always and are attempting many new treatments and research method, and but still the pathogenesis of clear and definite these diseases and treatment are not machine-processed.Along with the appearance and the application widely of light genetics neuromodulation technology in recent years, people go deep into gradually to the understanding of the problems referred to above, and some nervous system diseases that comprise parkinsonism have been had brand-new understanding.
So-called light genetics neuromodulation technology is a biotechnology of having integrated the multidisciplinary intersection of optics, gene engineering, electric physiology and electronic engineering that developed rapidly in recent years.Its cardinal principle is at first to adopt gene technology the light sensation gene to be transferred in the cell of particular type in the nervous system to express, and makes it form special ion channel on cell membrane.These ion channels can produce selectivity to cation or anionic passing through respectively under the light stimulation of different wave length, thereby cause the film potential on cell membrane both sides to change, and reach the purpose that pair cell is optionally excited or suppress.
Development along with light genetics neuromodulation technology, the specific neural circuit that people begin to zoologize more and more under light genetics regulation and control electric physiological characteristic and and behaviouristics between get in touch, thereby disclose the pathogenesis and the treatment mechanism of numerous nervous systems such as comprising epilepsy, schizophrenia, self-closing disease and mental illness.Yet what the behaviouristics test of traditional light genetics neuromodulation technology was mainly adopted is general testing arrangement, lacks a kind of behaviouristics test platform at light genetics neuromodulation.
[summary of the invention]
Based on this, be necessary to provide a kind of Animal Behavior Science test platform of regulating and control at the light genetics of light genetics neuromodulation art designs.
A kind of Animal Behavior Science test platform of smooth genetics regulation and control, be used for test animal is carried out the behaviouristics test, this test platform comprises central control system, environmental control system, behaviouristics monitoring system, Photoelectric Detection regulator control system and is used for fixing the casing device of said system; Described central control system links to each other with described environmental control system, behaviouristics monitoring system and Photoelectric Detection regulator control system, is used to control described environmental control system, behaviouristics monitoring system and Photoelectric Detection regulator control system; Described environmental control system is used to control illumination, gaseous environment, temperature and the damp condition of described test platform; Described behaviouristics monitoring system is used for the behavior of test animal is monitored and analyzed, and analysis result is fed back to described central control system; Described Photoelectric Detection regulator control system is used for test animal is carried out the detection of light regulation and control and electricity physiological signal, and the electricity physiological signal that detection obtains is fed back to described central control system.
In preferred embodiment, described environmental control system comprises illumination system and air circulation system, described illumination system is used to control light application time, illumination range and the intensity of illumination of described test platform, described air circulation system is used to control gaseous environment, the temperature and humidity condition of described test platform, and described air circulation system comprises blower that is fixed on the described casing device and the air outlet that is opened on the casing device.
In preferred embodiment, described behaviouristics monitoring system comprises camera and the recorder that is fixed on the described casing device.
In preferred embodiment, described Photoelectric Detection regulator control system comprises light regulator control system and electrode system, described smooth regulator control system carries out light stimulus regulation and control, the electricity physiological signal of described electrode system collecting test animal to the cell that test animal has imported photaesthesia type gene.
In preferred embodiment, described smooth regulator control system comprises LASER Light Source, fiber unit and fibre-optical splice; Described LASER Light Source links to each other with described fiber unit by fibre-optical splice, sends laser pulse to described fiber unit; Described fiber unit is implanted in the test animal body cell that has imported photaesthesia type gene is carried out the light stimulus regulation and control.
In preferred embodiment, described electrode system comprises electricity physiological signal register system, electrode contact and electrode unit; Described electrode unit is implanted the electricity physiological signal of gathering implant site in the test animal body; Described electricity physiological signal register system links to each other with described electrode unit by described electrode contact, and the electricity physiological signal of collecting electrode unit collection also feeds back to described central control system.
In preferred embodiment, described fibre-optical splice and described electrode contact are fixed together and form the photoelectricity joint.
In preferred embodiment, described fiber unit comprises at least one optical fiber, described electrode unit comprises at least one electrode, described fiber unit and described electrode unit are formed the optoelectronic pole array, and described fiber unit and described electrode unit are implanted in the test animal body by described optoelectronic pole array.
In preferred embodiment, also comprise the drug sustained release system that is used in the test animal body, injecting photaesthesia type gene or experiment medicine.
In preferred embodiment, described drug sustained release system is implanted in the test animal body by the miniflow conduit.
In preferred embodiment, described miniflow conduit and described optoelectronic pole array are fixed together and implant in the test animal body.
In preferred embodiment, also comprise the remote physiological monitoring system, described remote physiological monitoring system is monitored the physiological parameter of test animal by the implanted device of implanting in the test animal body.
In preferred embodiment, described casing device comprise at least the square body case that one side is made of transparent material and be located in the described shell the drinking water groove and for the netted base plate of test animal activity.
In preferred embodiment, described square shell inside or periphery are provided with the gauze screen that is used for shield electromagnetic signals.
By light genetics neuromodulation technology and electric physiology, behaviouristics test etc. are combined, a cover standardization and the integrated behaviouristics test platform that is used for the regulation and control of test animal light genetics have been set up, can be implemented in certain environment by this platform test animal is carried out regulation and control of light genetics and behaviouristics record, help to understand the relation between regulation and control of animal light genetics and the behaviouristics, satisfy the pathogenesis of nervous system and mental illness and the demand of treatment Mechanism Study.
[description of drawings]
Fig. 1 is the system module figure of Animal Behavior Science test platform of the light genetics regulation and control of an embodiment;
Fig. 2 is the schematic diagram of the Animal Behavior Science test platform of Fig. 1 light genetics regulation and control.
[embodiment]
Below mainly reach specific embodiment in conjunction with the accompanying drawings the Animal Behavior Science test platform of light genetics regulation and control be described in further detail.
As depicted in figs. 1 and 2, the Animal Behavior Science test platform 100 of the light genetics regulation and control of one preferred implementation is mainly used in test animal 800 is carried out the behaviouristics test, and it comprises central control system 110, environmental control system 120, behaviouristics monitoring system 130, Photoelectric Detection regulator control system 140, drug sustained release system 150, remote physiological monitoring system 160 and is used for fixing the casing device 170 of said system (removing long distance control system 160).Animal in the test animal 800 preferred grinding tooths is as small white mouse etc.
Photoelectric Detection regulator control system 140 comprises light regulator control system 142 and electrode system 144.Wherein, light regulator control system 142 is used for the cell that test animal 800 has imported photaesthesia type gene is carried out the light stimulus regulation and control; The electricity physiological signal of electrode system 144 collecting test animals 800, as, electrode is implanted to photaesthesia type cell peripheral, pass through light stimulation, electrode system is gathered the variation of the pericellular electricity physiological signal of photaesthesia type before and after the light stimulation, provides foundation thereby the effect of light stimulation further evaluated and tested.The electricity physiological signal of gathering can be single celled discharge or local field potentials signal etc.
Light regulator control system 142 comprises LASER Light Source 422, fibre-optical splice 424 and fiber unit 426.LASER Light Source 422 links to each other with fiber unit 426 by fibre-optical splice 424, sends laser pulse to fiber unit 426.Fiber unit 426 is implanted in test animal 800 bodies cell that has imported photaesthesia type gene is carried out the light stimulus regulation and control.
The fibre-optical splice 424 and the electrode contact 444 of present embodiment is fixed together and forms photoelectricity joint 450.LASER Light Source 422 is connected with electrode unit 446 with fiber unit 426 respectively by photoelectricity joint 450 with electricity physiological signal register system 442.Preferably, fiber unit 426 comprises at least one optical fiber, and electrode unit 446 comprises at least one electrode.The fiber unit 426 of present embodiment is formed optoelectronic pole array 460 with electrode unit 446, and fiber unit 426 and electrode unit 446 are implanted in the body of test animal 800 by optoelectronic pole array 460.
Drug sustained release system 150 is used in the body of test animal 800 injecting photaesthesia type gene, perhaps reagent such as injection experiments medicine.Photaesthesia type gene is transferred in the neuron of associated loop and expresses by special promotor.The genes of interest of photaesthesia type comprises excited type channel protein gene and inhibition type channel protein gene, and wherein, excited type channel protein gene such as ChR2, ChETA, VChR1 or SFOs are medium, inhibition type channel protein gene such as NpHR, Arch or MAC etc.When the target nerve unit to implant site carries out light stimulation, can cause the neuronic excitement or the inhibition of lead-in light sensitive gene, regulate and control neural circuit by the excited or inhibition of related neural unit, thereby implant site is carried out the light regulation and control.Because light stimulation only works to the neuronal cell of lead-in light sensitive gene, therefore, the light regulation and control have higher spatial and temporal resolution.
Drug sustained release system 150 mainly is implanted in the body of test animal 800 by miniflow conduit 152.Miniflow conduit 152 is the tubular structure of hard, and its composition can be metal materials such as plastic materials such as polytetrafluoroethylene (PTFE), polyimides, Teflon or stainless steel, platinum, platinumiridio, gold.The miniflow conduit 152 and the optoelectronic pole array 460 of present embodiment are fixed together and implant in the body of test animal 800.Preferably, can guide fiber unit 426, electrode unit 446 and miniflow conduits 152 with lead 470, fiber unit 426, electrode unit 446 and miniflow conduit 152 are implanted in the body of test animal 800 together, as being positions such as the head of test animal 800, vertebra.The implantation that is fixed together of fiber unit 426, electrode unit 446 and miniflow conduit 152 can be avoided in carrying out the behaviouristics test process, the problem that test animal 800 is turned round or electric wire and optical fiber twine when mobile.
Other preferred embodiment in, photaesthesia type gene also can be expressed by the specific region in test animal 800 bodies after the micro-injection of target location technology, in this case, this test platform 100 can not be provided with drug sustained release system 150, perhaps drug sustained release system 150 helps the Animal Behavior Science under the research specified conditions to change specially as the slow-released carrier of medicines such as anti-inflammatory medicine or nerve growth factor.
Remote physiological monitoring system 160 is carried out remote monitoring by the implanted device of implanting in test animal 800 bodies to the physiological parameter of test animal 800.As monitoring to physiological parameters such as the blood pressure of test animal 800, blood sugar, heartbeats.Remote monitoring can be undertaken by wired or wireless mode, undertaken by wireless mode, and mobility is stronger, and policer operation is convenient.
As shown in Figure 2, casing device 170 side's of being shapes of present embodiment comprise bottom surface, front-back and two sides.Front-back is made by transparent material, is convenient to observe.Two sides offer the air outlet 246 of strip.Environmental control system 120, behaviouristics monitoring system 130, Photoelectric Detection regulator control system 140, drug sustained release system 150 are arranged on the upper bottom surface of square shell.The inside of casing device 170 is provided with and is used to supply water and the drinking water groove 172 of food and the netted base plate 174 that supplies test animal 800 activities.Netted base plate 174 is an engraved structure, conveniently the excreta of test animal 800 is fallen into the space of the below of test platform 100, is convenient to sweep and excremental collection.
In specific implementation process, devices such as this test platform 100 can be tested with mining site, multi-arm labyrinth, water maze combine, and carry out corresponding behaviouristics experiment.Behaviouristics is observed for convenience, the casing device 170 of this test platform 100 can be all-glass construction, perhaps the front is a glass, other several times are metal or plastic construction, and can add the extraneous interference of gauze screen shielding in the outside of whole test platform 100, guarantee the accurate of electric physiology test data.
By light genetics neuromodulation technology and electric physiology, behaviouristics test etc. are combined, a cover standardization and the integrated behaviouristics test platform 100 that is used for the regulation and control of test animal light genetics have been set up, can be implemented in certain environment by this platform test animal is carried out regulation and control of light genetics and behaviouristics record, help to understand the relation between regulation and control of animal light genetics and the behaviouristics, satisfy the pathogenesis of nervous system and mental illness and the demand of treatment Mechanism Study.These test platform 100 structural design exquisitenesses can provide comparatively stable unique test environment for test animal 800.
The above embodiment has only expressed several embodiment of the present invention, and it describes comparatively concrete and detailed, but can not therefore be interpreted as the restriction to claim of the present invention.Should be pointed out that for the person of ordinary skill of the art without departing from the inventive concept of the premise, can also make some distortion and improvement, these all belong to protection scope of the present invention.Therefore, the protection domain of patent of the present invention should be as the criterion with claims.
Claims (14)
1. the Animal Behavior Science test platform of light genetics regulation and control, be used for test animal is carried out the behaviouristics test, it is characterized in that, comprise central control system, environmental control system, behaviouristics monitoring system, Photoelectric Detection regulator control system and be used for fixing the casing device of said system; Described central control system links to each other with described environmental control system, behaviouristics monitoring system and Photoelectric Detection regulator control system, is used to control described environmental control system, behaviouristics monitoring system and Photoelectric Detection regulator control system; Described environmental control system is used to control illumination, gaseous environment, temperature and the damp condition of described test platform; Described behaviouristics monitoring system is used for the behavior of test animal is monitored and analyzed, and analysis result is fed back to described central control system; Described Photoelectric Detection regulator control system is used for test animal is carried out the detection of light regulation and control and electricity physiological signal, and the electricity physiological signal that detection obtains is fed back to described central control system.
2. the Animal Behavior Science test platform of smooth genetics regulation and control as claimed in claim 1, it is characterized in that, described environmental control system comprises illumination system and air circulation system, described illumination system is used to control light application time, illumination range and the intensity of illumination of described test platform, described air circulation system is used to control gaseous environment, the temperature and humidity condition of described test platform, and described air circulation system comprises blower that is fixed on the described casing device and the air outlet that is opened on the casing device.
3. the Animal Behavior Science test platform of smooth genetics regulation and control as claimed in claim 1 is characterized in that described behaviouristics monitoring system comprises camera and the recorder that is fixed on the described casing device.
4. the Animal Behavior Science test platform of smooth genetics regulation and control as claimed in claim 1, it is characterized in that, described Photoelectric Detection regulator control system comprises light regulator control system and electrode system, described smooth regulator control system carries out light stimulus regulation and control, the electricity physiological signal of described electrode system collecting test animal to the cell that test animal has imported photaesthesia type gene.
5. the Animal Behavior Science test platform of smooth genetics regulation and control as claimed in claim 4 is characterized in that described smooth regulator control system comprises LASER Light Source, fiber unit and fibre-optical splice; Described LASER Light Source links to each other with described fiber unit by fibre-optical splice, sends laser pulse to described fiber unit; Described fiber unit is implanted in the test animal body cell that has imported photaesthesia type gene is carried out the light stimulus regulation and control.
6. the Animal Behavior Science test platform of smooth genetics regulation and control as claimed in claim 5 is characterized in that described electrode system comprises electricity physiological signal register system, electrode contact and electrode unit; Described electrode unit is implanted the electricity physiological signal of gathering implant site in the test animal body; Described electricity physiological signal register system links to each other with described electrode unit by described electrode contact, and the electricity physiological signal of collecting electrode unit collection also feeds back to described central control system.
7. the Animal Behavior Science test platform of smooth genetics regulation and control as claimed in claim 6 is characterized in that, described fibre-optical splice and described electrode contact are fixed together and form the photoelectricity joint.
8. the Animal Behavior Science test platform of smooth genetics regulation and control as claimed in claim 7, it is characterized in that, described fiber unit comprises at least one optical fiber, described electrode unit comprises at least one electrode, described fiber unit and described electrode unit are formed the optoelectronic pole array, and described fiber unit and described electrode unit are implanted in the test animal body by described optoelectronic pole array.
9. the Animal Behavior Science test platform of smooth genetics regulation and control as claimed in claim 8 is characterized in that, also comprises the drug sustained release system that is used for injecting photaesthesia type gene or experiment medicine in the test animal body.
10. the Animal Behavior Science test platform of smooth genetics regulation and control as claimed in claim 9 is characterized in that described drug sustained release system is implanted in the test animal body by the miniflow conduit.
11. the Animal Behavior Science test platform of smooth genetics regulation and control as claimed in claim 10 is characterized in that, described miniflow conduit and described optoelectronic pole array are fixed together and implant in the test animal body.
12. Animal Behavior Science test platform as claim 1 or 11 described smooth genetics regulation and control, it is characterized in that, also comprise the remote physiological monitoring system, described remote physiological monitoring system is monitored the physiological parameter of test animal by the implanted device of implanting in the test animal body.
13. Animal Behavior Science test platform as claim 1 or 11 described smooth genetics regulation and control, it is characterized in that, described casing device comprise at least the square body case that one side is made of transparent material and be located in the described shell the drinking water groove and for the netted base plate of test animal activity.
14. the Animal Behavior Science test platform of smooth genetics regulation and control as claimed in claim 13 is characterized in that described square shell inside or periphery are provided with the gauze screen that is used for shield electromagnetic signals.
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