CN106687587A - Acoustic sensitive ion channel genetic manipulation method and system - Google Patents
Acoustic sensitive ion channel genetic manipulation method and system Download PDFInfo
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- CN106687587A CN106687587A CN201580000405.8A CN201580000405A CN106687587A CN 106687587 A CN106687587 A CN 106687587A CN 201580000405 A CN201580000405 A CN 201580000405A CN 106687587 A CN106687587 A CN 106687587A
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Abstract
The invention provides an acoustic sensitive ion channel genetic manipulation method and system. The method comprises steps of acquiring an acoustic wave (101); focusing the acoustic wave on an endogenous mechanically sensitive ion channel of the nerve cell to be stimulated, opening the endogenous mechanical sensitive ion channel, and /or focusing the acoustic wave on the exogenous mechanically sensitive ion channel of the nerve cell to be stimulated, opening the exogenous mechanical sensitive ion channel, and altering the membrane potential (102) of the nerve cell. The scheme achieves noninvasive, accurate, and selective specific neural manipulation and regulation in a sound wave.
Description
Technical field
The present invention relates to cranial nerve stimulating technology field, more particularly to a kind of acoustic sensing ion channel genetic manipulation method and
System.
Background technology
The effective prevention of the cerebral dysfunction diseases such as Parkinson's, epilepsy and depression and treatment are a significant medical difficult problems.By
Huge in China human mortality radix and aging is improved year by year, the quantity of these cerebral diseases patient is up to tens of millions of people,
Jing becomes the heavy financial burden of China and thorny social concern.Brain caused by the main pathological change of functional brain disease
The dysfunction of deep nuclei and neural circuitry.But, it is still unclear to the exact mechanism of functional brain disease at present,
And lacking effective remedy measures, this remains the medical challenge of global facing.Therefore, these cerebral diseases are recognized
Pathogenesis and develop the great and urgent task that advanced intervention and treatment technology are scientific circles.
It is to understand functional brain disease incidence mechanism and it is done that the nerve nucleus in brain deep stimulate with loop regulation and control
Pre- and treatment important channel, is also the great advanced problems of current brain science research.Research shows, functional brain disease
The generation of disease is relevant with specific " the cortical-basal ganglionic brain loop " dysfunction of big intracerebral, stimulates corresponding
Target spot can cause cortex and Descending fibers to change so as to mitigate or cure symptom by corresponding loop, and this is further investigation
The neuromodulations such as the mechanism and DBS of functional brain disease provide scientific basis with intervention means.
Neural circuitry is predominantly located between (6～10cm) nerve nucleus of cerebral deep, is that big intracerebral micro molecule is thin
Close ties passage between born of the same parents and macroscopical global behavior, is also research intracerebral molecular cell function and global behavior function
Between crucial bridge.The different units of simple function loop may span across multiple structures, and spatially with other work(
Energy loop interacts.The activity of the feedback information of high-level center modulation function loop without interruption, produced chemistry is passed
Qualitative changeization may then change the effectively connection mode of function loop.Therefore, DBS and neural circuitry regulation and control are brains
One of science and the core content of cerebral disease research.
Nerve stimulation and the important motivity that the technology and instrument of loop regulation and control are promotion Neuscience development.After 1870
Germany scientist reports the cerebral cortex of dog under electro photoluminescence can be caused in more than 100 years after specific Tenseness,
The technologies such as electricity, magnetic, light generate the god such as deep brain stimulation, Neural stem cell, photogene regulation and control in combination with Neuscience
Jing stimulates and control technique.
Lesions located in deep brain (Deep Brain Stimulation, DBS) is the specific nerve nucleus of intracerebral for being implanted at electrode
Group's target spot, the abnormal neuron function of suppressing target cell is stimulated by controllable high frequency electric, is reached effective prevention and is controlled
Treat the purpose of disease【With reference to the A of Chinese patent CN 102470247, the A of CN 102762253】.From 1987 first
Since being used for the control trembled, the whole world have more than 10 ten thousand patients implant DBS devices (also known as " and brain pace
Device "), it is numerous intractable cerebral diseases such as Parkinson's, depression, intractable epilepsy, Muscle tensility imbalance, stubbornness
Property pain, obsession etc. provide a kind of effective interference method【Halpem CH,Samadani U,Litt B,et a1.
Deep brain stimulation for epilepsy.Neurotherapeutics,2008,5(1)：59-67】.But, DBS
Application there is also important limitation：Clinically by operation of opening cranium by 1～2 electrode implantation depth brain tissue for core group
It is to cause permanent wound, target spot to change brain tissue and neural circuitry, be difficult to more multiple location to carry out stimulation
The stimulation of core group, and entirely power supply supply equipment also will be surgically implanted into body.In the thorn that individual brain applies
Sharp electrode can affect the normal function of body, after DBS electrodes are using a period of time, in surrounding them glue can be formed
Cell plastid sheath, not only affects the efficiency of electrode, can also affect the normal function of body, and, when electro photoluminescence is applied,
The electro photoluminescence for being applied always causes excitability to react, and only when stimulating inhibition core to roll into a ball, can just cause inhibition anti-
Should, these shortcomings also limit application of the electrical stimulation technology in terms of regulation and control neural circuitry.
Jing cranium galvanic current stimulations (transcranial direct current stimulatioin, tDCS) and transcranial magnetic stimulation
Technologies such as (transcranial magnetic stimulation, TMS) is painless noninvasive detection and treatment technology.Before
Person is input into constant current via the scalp adhesive electrode piece of two salt water-soakeds to encephalic specific region, changes brain surface
The depolarising of membrane potential of neurons or hyperpolarization direction, so as to change spontaneous neururgic cortical excitability【With reference in
The U of state's patent CN 202538169】.Instantaneous, the high deep-sited pulse punching that TMS is produced by the magnetic coil being positioned on scalp
A magnetic field domain perpendicular to coil plane is produced, almost without scalp and skull is damply passed through, the deep of brain is reached
Induced-current is organized and produced, neuronal depolarization is made and is produced Evoked ptential.By pulse, dipulse and weight
Multiple transcranial magnetic stimulation isotype, regulates and controls the excited or rejection characteristic of nerve cell, so as to adjust the function of cortex【With reference to
The A of Chinese patent CN 102462892, with reference to United States Patent (USP) US 6827681 B2, Kirton A, Chen R, Friefeld
S,Gunraj C,Pontigon A-M,et al.(2008)Contralesional repetitive transcranial magnetic
stimulation for chronic hemiparesis in subcortical paediatric stroke:a randomised trial.The
Lancet Neurology 7:507-513.】.Two kinds of technologies are used to evaluate Electrophysiology conduction path, and depressed
The neurological rehabilitation treatment of the diseases such as disease, epilepsy, apoplexy, schizophrenia, self-closing disease.
The light genetics technology (Optogenetics) for growing up emerging during the nearly last ten years, realizes in cellular level
The a certain microcircuit of selective regulation, i.e., realize the excitability to a certain loop or suppression by giving the laser of different wave length
Property regulation and control processed, have effectively promoted the development of Neuscience【With reference to Chinese patent CN 103168236A】.But,
Light genetics technology is to activate photaesthesia passage by giving the laser of different wave length, because biological tissue is for light
It is strong to absorb the propagation distance (only some millimeters) for seriously limiting light, it is therefore desirable in patient or tested animal
Corresponding brain area insertion optical fiber and fibre-optic catheter, this inevitably damaged portion brain area in operation, so as to cause god
Some physiological functions of Jing systems are lost.Meanwhile, the photaesthesia channel protein that depends critically on of light genetics technology (turns
Catch an illness poison realize) expression, be currently only used for Neuscience small animal model (mouse) experimental study.But for
The senior big animal of non-human primates still has no report, and the technology faces the challenge of complexity.
Trace drug pump technology (Drug Delivery Pump) in exact position by being implanted into what pump installation was directly administered
Means are realizing neuromodulation【With reference to the B1 of United States Patent (USP) US 6609030】.Because medicine is applied directly to local,
Dosage is effectively reduced, side effect is reduced.For a long time treatment is had become using Baclofen by implantable pump intrathecal
The basic skills of the spasm of intractable spinal cord or cerebral origin.Light sensation gene neuromodulation (Optogenetics) is to explore
The powerful of neural circuitry【20140142664 A1 of A, US of referenced patent CN 102283145】.It is substantially former
Reason is that opsin gene is imported into specific neuronal populations by virus transfection plus specific promoter, and by difference
The light stimulus of parameter changing the physiological activity of the neuron, so as to realize the regulation and control of affiliated nerve pathway.
TCD,transcranial Doppler neuromodulation is the non-invasive brain stimulation new technology for occurring in recent years, by different intensity, frequency,
Pulse recurrence frequency, pulse width, duration make the nervous centralis of stimulation location produce stimulation or depression effect, right
Nervous function produces the invertibity change of bidirectional modulation【Referenced patent US 20130197401, US20110092800】.
Recently, Arizona State University group demonstrates low-frequency and low-voltage ultrasonic wave induction nerve by the experiment of mouse cerebral hippocampal piece
Regulation and control, and it is also proposed that possible regulatory mechanism, i.e., the valtage-gated sodium ion of ultrasonic wave action and calcium channel
【Tyler WJ,Tufail Y,Finsterwald M,Tauchmann ML,Olson EJ,et al.(2008)Remote
excitation of neuronal circuits using low-intensity,low-frequency ultrasound.PLoS One 3:
e3511.】.Later, group's first passage living animal experiment is demonstrated and realizes nerve using low-frequency and low-voltage ultrasonic wave
Regulation and control【Tufail Y,Matyushov A,Baldwin N,Tauchmann ML,Georges J,et al.(2010)
Transcranial pulsed ultrasound stimulates intact brain circuits.Neuron 66:681-694.】.Fu Ji
It is special that low-frequency and low-voltage ultrasonic wave is directly acted on brain by Legon Wynn of Carilion research institutes of Ni Ya Polytechnics etc.
Determine region, resolution capability of the people to tactile can be strengthened.This finds to demonstrate low-intensity, Jing craniums for the first time and focus on to surpass
Sound wave can adjust mankind's cerebration, improve detection ability【Legon W,Sato TF,Opitz A,Mueller J,Barbour
A,et al.(2014)Transcranial focused ultrasound modulates the activity of primary
somatosensory cortex in humans.Nature neuroscience 17:322-329.】。
Although the clinical or scientific experiment effect of above-mentioned brain stimulation and neuromodulation technology is affirmed, its effect machine
System is unclear.It is now recognized that lesions located in deep brain changes the activity of voltage-gated channel, neurotransmitter is exhausted, from
And the transmission of cynapse information is hindered, the nerve signal for having prevented surrounding them is exported, and the core group to being stimulated generates
Feature damages effect；Stimulation adjusts god in the axon terminal for having synaptic contact with surrounding them neuron, indirectly
The output of Jing signals, and then change pathologic neutral net function.
Above-mentioned various brain stimulation devices still suffer from many limitation and technological challenge.For example, DBS is invasive skill
Art, device and surgery cost are expensive, there is certain postoperative complication, target spot tolerance, rejection equivalent risk, supply
Electric battery life is 4-5, and must perform the operation again replacing battery or internal stimulus device after running down of battery, to user
Bigger painful and financial burden is caused, the popularization of DBS is greatly limit.Light genetics technology due to
Transfected virus albumen is needed, so being not used to clinical cerebral disease treatment.Noninvasive tDCS and TMS technologies are outer right
Operator and experiment condition requirement are higher, and as a result treated frequency, stimulation location, stimulation duration, the state of an illness are tight
The factors such as weight degree, drug therapy situation affect, and therapeutic evaluation is still disputable.There is limitation in light sensation gene neuromodulation
Property, wide field stimulus modality is such as adopted, though can activate or inhibitory neuron, it can be whole animal sample or whole god
Jing loop activations, it is impossible to realize specific cells or a group cell selective light stimulus activation；As using based on scanning mirror,
Acousto-optic deflection device, light emitting diode matrix, spatial light modulator, liquid crystal or micro mirror technology, though be capable of achieving high
The stimulation active cell of space division resolution, but generally have to, with reference to being inverted or just putting on fluorescence microscope, be only applicable to culture
The light stimulus activation of cell, brain section, has that light stimulus scope is little, is not suitable for studying big neutral net and regulation and control are lived
The behavioral activity of body animal.These limit application of the light sensation gene neuromodulation technology in neural circuitry research.This
Outward, although TCD,transcranial Doppler neuromodulation technology realizes cranial nerve stimulation using low-frequency and low-voltage ultrasonic wave, but at present
The mechanism of neuromodulation specifically how is not carried out using ultrasonic wave, to realize noninvasive, accurately cranial nerve stimulation.
The content of the invention
A kind of acoustic sensing ion channel genetic manipulation method is embodiments provided, to realize noninvasive, accurate, choosing
Select the nerve operation of specificity and regulate and control.The method includes：Obtain sound wave；The sound wave is focused on into god to be stimulated
On the endogenous mechanosensitive ion channels of Jing cells, the opening endogenous mechanosensitive ion channels；With/
Or, the sound wave is focused on the exogenous mechanosensitive ion channels of nerve cell to be stimulated, it is open described
Exogenous mechanosensitive ion channels.
In one embodiment, the sound wave is focused on the exogenous mechanosensitive ion of nerve cell to be stimulated
On passage, including：Expressed by the way that acoustic sensing gene is transfected on nerve cell to be stimulated, made the external source
Property mechanosensitive ion channels are transferred on the cell membrane of the nerve cell；The sound wave is focused on after the transfer
On exogenous mechanosensitive ion channels.
In one embodiment, the sound wave is ultrasonic wave.
In one embodiment, the nerve cell is thin including the nerve cell in deep brain area domain and the nerve in shallow brain area domain
Born of the same parents.
In one embodiment, the acoustic pressure of the sound wave is more than or equal to 1 kPa.
The embodiment of the present invention also provides a kind of acoustic sensing ion channel genetic operating system, noninvasive, accurately right to realize
The operation and regulation and control of selective specific neuronal.The system includes：Sound wave generation device, for producing sound wave；Sound wave is passed
Broadcasting device, for by the sonic transmissions to nerve cell to be stimulated, the sound wave to focus on nerve to be stimulated
On the endogenous mechanosensitive ion channels of cell, the opening endogenous mechanosensitive ion channels, and/or
The sound wave is focused on the exogenous mechanosensitive ion channels of nerve cell to be stimulated, and opening is described exogenous
Mechanosensitive ion channels, change the film potential of the nerve cell.
In one embodiment, the exogenous mechanosensitive ion channels be acoustic sensing gene is transfected into it is described
After being expressed on nerve cell, the exogenous mechanosensitive ion being transferred on the cell membrane of the nerve cell leads to
Road.
In one embodiment, the sound wave is ultrasonic wave.
In one embodiment, the nerve cell is thin including the nerve cell in deep brain area domain and the nerve in shallow brain area domain
Born of the same parents.
In one embodiment, the acoustic pressure of the sound wave is more than or equal to 1 kPa.
In the embodiment of the present invention, by the endogenous mechanosensitive ion channels that sound wave is focused on nerve cell,
It is quick with the open endogenous mechanosensitive ion channels, and/or the exogenous machinery that sound wave is focused on into nerve cell
On perceptual ion channel, with the open exogenous mechanosensitive ion channels so that change the film electricity of the nerve cell
Position, and then reach the purpose that or suppression excited to nerve cell is regulated and controled.Because sound wave is by mechanical force activation god
Jing is first, but voltage-gated sodium and calcium channel are not classical mechanical sensitivity albumen, therefore, the application
Propose by sound wave focus on the endogenous mechanosensitive ion channels and/or exogenous mechanical sensitivity of nerve cell from
On subchannel, so as to nerve operation that is noninvasive, accurate, selecting specificity being realized in the way of sound wave and being regulated and controled.
Description of the drawings
Accompanying drawing described herein is used for providing a further understanding of the present invention, constitutes the part of the application, not
Constitute limitation of the invention.In the accompanying drawings：
Fig. 1 is a kind of flow chart of acoustic sensing ion channel genetic manipulation method provided in an embodiment of the present invention；
Fig. 2 is the schematic diagram that a kind of mechanosensitive ion channels provided in an embodiment of the present invention are opened；
Fig. 3 is a kind of schematic diagram of sound wave provided in an embodiment of the present invention；
Fig. 4 is a kind of structure chart of acoustic sensing ion channel genetic operating system provided in an embodiment of the present invention.
Specific embodiment
To make the object, technical solutions and advantages of the present invention become more apparent, with reference to embodiment and accompanying drawing,
The present invention is described in further details.Here, the exemplary embodiment of the present invention and its illustrating for explaining this
It is bright but not as a limitation of the invention.
In embodiments of the present invention, there is provided a kind of flow chart of acoustic sensing ion channel genetic manipulation method, such as Fig. 1
Shown, the acoustic sensing ion channel genetic manipulation method can include：
Step 101：Obtain sound wave；
Step 102：Sound wave wears cranium focusing, and the endogenous machinery that the sound wave is focused on into nerve cell to be stimulated is quick
On perceptual ion channel, the opening endogenous mechanosensitive ion channels；And/or, the sound wave is focused on
On the exogenous mechanosensitive ion channels of nerve cell to be stimulated, the opening exogenous mechanosensitive ion
Passage.
By Fig. 1 it is known that in embodiments of the present invention, by the endogenous machinery that sound wave is focused on nerve cell
On sensitiveness ion channel, the endogenous mechanosensitive ion channels can be opened, and/or sound wave is focused on into god
On the exogenous mechanosensitive ion channels of Jing cells, to open the exogenous mechanosensitive ion channels, for example,
As shown in Fig. 2 mechanosensitive ion channels (i.e. endogenous mechanosensitive ion channels or the external source of mid portion
Property mechanosensitive ion channels) it is open in the presence of sound wave, arrow represents that mechanosensitive ion channels are stretched into
And open so that change the film potential of nerve cell, and then reach the mesh that or suppression excited to nerve cell is regulated and controled
, because sound wave is to activate neuron by mechanical force, but valtage-gated sodium ion and calcium channel are not
Classical mechanical sensitivity albumen, therefore, the application proposes the endogenous mechanical sensitivity that sound wave is focused on nerve cell
It is noninvasive, accurately so as to be realized in the way of sound wave on ion channel and/or exogenous mechanosensitive ion channels
Operation and regulation and control to selective specific neuronal, the research and treatment and Neuroscience Research for cerebral disease provides one
Plant the instrument of innovation.
When being embodied as, in order to realize sound wave can through skull focus on the endogenous mechanical sensitivity of nerve cell from
On subchannel and/or exogenous mechanosensitive ion channels, in the present embodiment, above-mentioned sound wave effect is in cell membrane
On acoustic pressure be more than or equal to 1 kPa.Specifically, above-mentioned sound wave can be ultrasonic wave, and the acoustic wave sequences of ultrasonic wave are as schemed
Shown in 3.
When being embodied as, the radiant force of sound wave needed in order to reduce the exogenous mechanosensitive ion channels of opening, at this
In embodiment, the sound wave is focused on the exogenous mechanosensitive ion channels of nerve cell to be stimulated, wrapped
Include：Expressed by the way that acoustic sensing gene is transfected on nerve cell to be stimulated, made the exogenous mechanical sensitivity
Property ion channel transfer is on the cell membrane of the nerve cell；By sound wave focusing exogenous machinery after the transfer
On sensitiveness ion channel.I.e. after nerve cell transfection acoustic sensing gene is expressed, in less acoustic irradiation power
Effect is lower can to open the exogenous mechanosensitive ion channels after transfer, so as to the film potential for causing nerve cell is sent out
Changing, reaches regulation and control purpose that is optionally excited to nerve cell or suppressing.
When being embodied as, the nerve cell that above-mentioned sound wave is focused on can be the nerve cell in deep brain area domain, or shallow
The nerve cell in brain area domain, so that whole brain region can be realized in Different brain region domain cranial nerve stimulate.
Specifically, above-mentioned exogenous mechanosensitive ion channels (or acceptor) can include from all algae, bacterium,
The gene extracted in virus, actinomyces, fungi, protozoan and various animals and/or albumen.
When being embodied as, a kind of acoustic sensing ion channel genetic operating system, such as Fig. 4 are additionally provided in the present embodiment
Shown, the acoustic sensing ion channel genetic operating system includes：
Sound wave generation device 401, for producing sound wave；
Acoustic Wave Propagation device 402, for by the sonic transmissions to nerve cell to be stimulated, the sound wave to be focused on
On the endogenous mechanosensitive ion channels of nerve cell to be stimulated, the opening endogenous mechanical sensitivity from
Subchannel, and/or the sound wave is focused on the exogenous mechanosensitive ion channels of nerve cell to be stimulated,
The opening exogenous mechanosensitive ion channels, change the film potential of the nerve cell.
Specifically, as shown in figure 4, the sound wave generation device 401 includes：Signal generator 4011, for producing
Radiofrequency signal, for example, the signal generator 4011 can be single array element ultrasonic transducer, pin type ultrasonic transducer,
Many array element faces battle array, cambered surface battle array ultrasonic transducer, ultrasonic surface wave chip or minisize condenser type supersonic transducer CMUT；
Power amplifier 4012, for carrying out power amplification to the radiofrequency signal；Match circuit 4013, for for amplify
Radiofrequency signal afterwards selects passage used when exporting in ultrasonic probe, and time delay is arranged between different passages, amplifies
The different sound that the ultrasonic probe is generated of the passage used when exporting in the ultrasonic probe of radiofrequency signal afterwards
The focus point of ripple is different, for example, when institute can be exported in the ultrasonic probe by the radiofrequency signal after adjustment is amplified
Passage come realize to ultrasonic probe generate sound wave focus position adjustment；The ultrasonic probe 4014, uses
In being the passage that the radiofrequency signal after the amplification is selected and the time delay for arranging according to the match circuit, by the amplification
Radiofrequency signal afterwards is converted into sound wave, and for example, the material of the ultrasonic probe 4014 can be monocrystalline piezoelectric material, pressure
The piezoelectric such as electroceramics material or thin films of piezoelectric material.
When being embodied as, in order to realize sound wave can through skull focus on the endogenous mechanical sensitivity of nerve cell from
On subchannel and/or exogenous mechanosensitive ion channels, in the present embodiment, the acoustic pressure of above-mentioned sound wave more than etc.
In 1 kPa.Specifically, above-mentioned sound wave can be ultrasonic wave, the acoustic wave sequences of ultrasonic wave as shown in figure 3, now,
Acoustic Wave Propagation device 402 be ultrasonic coupling agent, the ultrasonic coupling agent between sound wave generation device 401 and skull away from
From interior air-isolation so that ultrasonic wave can be traveled at skull, and then the endogenous of nerve cell is focused on through skull
On property mechanosensitive ion channels and/or exogenous mechanosensitive ion channels.
When being embodied as, the radiant force of sound wave needed in order to reduce the exogenous mechanosensitive ion channels of opening, at this
In embodiment, the exogenous mechanosensitive ion channels are that acoustic sensing gene is being transfected on the nerve cell
After being expressed, the exogenous mechanosensitive ion channels being transferred on the cell membrane of the nerve cell.
When being embodied as, the nerve cell that above-mentioned sound wave is focused on can be the nerve cell in deep brain area domain, or shallow
The nerve cell in brain area domain, to realize whole brain region in Different brain region domain cranial nerve stimulate.
In embodiments of the present invention, by the way that sound wave to be focused on the endogenous mechanosensitive ion channels of nerve cell
On, with the open endogenous mechanosensitive ion channels, and/or sound wave is focused on into the exogenous machine of nerve cell
On tool sensitiveness ion channel, with the open exogenous mechanosensitive ion channels so that change the nerve cell
Film potential, and then reach the purpose that or suppression excited to nerve cell is regulated and controled.Because sound wave is swashed by mechanical force
Neuron living, but voltage-gated sodium and calcium channel are not classical mechanical sensitivity albumen, therefore, this
Application proposes the endogenous mechanosensitive ion channels and/or exogenous mechanical sensitivity that sound wave is focused on nerve cell
On property ion channel, so as to realized in the way of sound wave it is noninvasive, accurately to the operation and regulation and control of selective specific neuronal.
Those skilled in the art are it should be appreciated that embodiments of the invention can be provided as method, system or computer journey
Sequence product.Therefore, the present invention can adopt complete hardware embodiment, complete software embodiment or combine software and hardware
The form of the embodiment of aspect.And, the present invention can be adopted and wherein include computer available programs at one or more
The computer-usable storage medium (including but not limited to magnetic disc store, CD-ROM, optical memory etc.) of code
The form of the computer program of upper enforcement.
The present invention is the stream with reference to method according to embodiments of the present invention, equipment (system) and computer program
Journey figure and/or block diagram are describing.It should be understood that can be by computer program instructions flowchart and/or block diagram
The combination of each flow process and/or square frame and flow chart and/or the flow process in block diagram and/or square frame.These can be provided
Computer program instructions are processed to all-purpose computer, special-purpose computer, Embedded Processor or other programmable datas and set
Standby processor is producing a machine so that held by the processor of computer or other programmable data processing devices
Capable instruction is produced for realizing in one flow process of flow chart or one square frame of multiple flow processs and/or block diagram or multiple sides
The device of the function of specifying in frame.
These computer program instructions may be alternatively stored in can guide computer or other programmable data processing devices with spy
In determining the computer-readable memory that mode works so that the instruction being stored in the computer-readable memory produces bag
The manufacture of command device is included, the command device is realized in one flow process of flow chart or multiple flow processs and/or block diagram one
The function of specifying in individual square frame or multiple square frames.
These computer program instructions also can be loaded into computer or other programmable data processing devices so that in meter
Series of operation steps is performed on calculation machine or other programmable devices to produce computer implemented process, so as to calculate
The instruction performed on machine or other programmable devices provide for realizing in one flow process of flow chart or multiple flow processs and/or
The step of function of specifying in one square frame of block diagram or multiple square frames.
The preferred embodiments of the present invention are the foregoing is only, the present invention is not limited to, for the skill of this area
For art personnel, the embodiment of the present invention can have various modifications and variations.It is all within the spirit and principles in the present invention,
Any modification, equivalent substitution and improvements made etc., should be included within the scope of the present invention.
Claims (10)
1. a kind of acoustic sensing ion channel genetic manipulation method, it is characterised in that include：
Obtain sound wave；
The sound wave is focused on the endogenous mechanosensitive ion channels of nerve cell to be stimulated, it is open described
Endogenous mechanosensitive ion channels；And/or, the sound wave is focused on into the exogenous of nerve cell to be stimulated
On mechanosensitive ion channels, the opening exogenous mechanosensitive ion channels.
2. the method for claim 1, it is characterised in that the sound wave is focused on into nerve to be stimulated thin
On the exogenous mechanosensitive ion channels of born of the same parents, including：
Expressed by the way that acoustic sensing gene is transfected on nerve cell to be stimulated, made the exogenous mechanical sensitivity
Property ion channel transfer is on the cell membrane of the nerve cell；
The sound wave is focused on exogenous mechanosensitive ion channels after the transfer.
3. method as claimed in claim 1 or 2, it is characterised in that the sound wave is ultrasonic wave.
4. method as claimed in claim 1 or 2, it is characterised in that the nerve cell includes deep brain area domain
Nerve cell and the nerve cell in shallow brain area domain.
5. method as claimed in claim 1 or 2, it is characterised in that the acoustic pressure of the sound wave is more than or equal to 1,000
Handkerchief.
6. a kind of acoustic sensing ion channel genetic operating system, it is characterised in that include：
Sound wave generation device, for producing sound wave；
Acoustic Wave Propagation device, for by the sonic transmissions to nerve cell to be stimulated, the sound wave is focused on to be treated
On the endogenous mechanosensitive ion channels of the nerve cell of stimulation, the opening endogenous mechanosensitive ion leads to
Road, and/or the sound wave focused on the exogenous mechanosensitive ion channels of nerve cell to be stimulated, it is open
The exogenous mechanosensitive ion channels, change the film potential of the nerve cell.
7. system as claimed in claim 6, it is characterised in that the exogenous mechanosensitive ion channels are
After acoustic sensing gene to be transfected into expressed on the nerve cell, it is transferred on the cell membrane of the nerve cell
Exogenous mechanosensitive ion channels.
8. system as claimed in claims 6 or 7, it is characterised in that the sound wave is ultrasonic wave.
9. system as claimed in claims 6 or 7, it is characterised in that the nerve cell includes deep brain area domain
Nerve cell and the nerve cell in shallow brain area domain.
10. system as claimed in claims 6 or 7, it is characterised in that the acoustic pressure of the sound wave is more than or equal to 1
KPa.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| PCT/CN2015/088706 WO2017035767A1 (en) | 2015-09-01 | 2015-09-01 | Method and system for genetic manipulation of sound-sensitive ion channels |
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|---|---|---|---|---|
| CN103028202A (en) * | 2012-12-26 | 2013-04-10 | 上海交通大学 | Transcranial ultrasound stimulation cranial-nerve-function-repairing device and method |
| CN103432691A (en) * | 2013-08-13 | 2013-12-11 | 北京师范大学 | Transcranial ultrasonic brain regulating and controlling method and device |
| CN104548390A (en) * | 2014-12-26 | 2015-04-29 | 中国科学院深圳先进技术研究院 | Ultrasound deep brain stimulation method and system |
| CN104826243A (en) * | 2015-05-15 | 2015-08-12 | 深圳先进技术研究院 | Device for ultrasonic stimulation of neural tissue |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN103028202A (en) * | 2012-12-26 | 2013-04-10 | 上海交通大学 | Transcranial ultrasound stimulation cranial-nerve-function-repairing device and method |
| CN103432691A (en) * | 2013-08-13 | 2013-12-11 | 北京师范大学 | Transcranial ultrasonic brain regulating and controlling method and device |
| CN104548390A (en) * | 2014-12-26 | 2015-04-29 | 中国科学院深圳先进技术研究院 | Ultrasound deep brain stimulation method and system |
| CN104826243A (en) * | 2015-05-15 | 2015-08-12 | 深圳先进技术研究院 | Device for ultrasonic stimulation of neural tissue |
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| TYLER等: "Remote Excitation of Neuronal Circuits Using Low-Intensity, Low-Frequency Ultrasound", 《PLOS ONE》 * |
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