CN107912326A - Animal behavior training method and training device - Google Patents
Animal behavior training method and training device Download PDFInfo
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- CN107912326A CN107912326A CN201610886014.7A CN201610886014A CN107912326A CN 107912326 A CN107912326 A CN 107912326A CN 201610886014 A CN201610886014 A CN 201610886014A CN 107912326 A CN107912326 A CN 107912326A
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- 238000012549 training Methods 0.000 title claims abstract description 89
- 238000000034 method Methods 0.000 title claims abstract description 50
- 230000006399 behavior Effects 0.000 claims abstract description 35
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 228
- 230000003936 working memory Effects 0.000 claims description 22
- 239000002516 radical scavenger Substances 0.000 claims description 8
- 239000003651 drinking water Substances 0.000 claims description 6
- 235000020188 drinking water Nutrition 0.000 claims description 6
- 238000006073 displacement reaction Methods 0.000 claims description 5
- 230000001186 cumulative effect Effects 0.000 claims description 4
- 238000004891 communication Methods 0.000 claims description 3
- 230000003111 delayed effect Effects 0.000 claims description 3
- 238000005303 weighing Methods 0.000 claims description 3
- 238000011017 operating method Methods 0.000 claims description 2
- 230000003542 behavioural effect Effects 0.000 abstract description 8
- 230000007087 memory ability Effects 0.000 abstract description 4
- 230000035943 smell Effects 0.000 description 37
- 201000010099 disease Diseases 0.000 description 15
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 15
- 238000011160 research Methods 0.000 description 9
- 238000010171 animal model Methods 0.000 description 7
- 238000010586 diagram Methods 0.000 description 7
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- 210000002442 prefrontal cortex Anatomy 0.000 description 3
- 208000024891 symptom Diseases 0.000 description 3
- 208000018152 Cerebral disease Diseases 0.000 description 2
- 210000004556 brain Anatomy 0.000 description 2
- 238000004140 cleaning Methods 0.000 description 2
- 230000003920 cognitive function Effects 0.000 description 2
- 230000007423 decrease Effects 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 238000009509 drug development Methods 0.000 description 2
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- 230000035479 physiological effects, processes and functions Effects 0.000 description 2
- 238000012827 research and development Methods 0.000 description 2
- 230000035945 sensitivity Effects 0.000 description 2
- 208000024827 Alzheimer disease Diseases 0.000 description 1
- 206010008190 Cerebrovascular accident Diseases 0.000 description 1
- 208000006011 Stroke Diseases 0.000 description 1
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- 230000001149 cognitive effect Effects 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 230000001934 delay Effects 0.000 description 1
- 230000007357 depressive behavior Effects 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 229940000406 drug candidate Drugs 0.000 description 1
- 230000005611 electricity Effects 0.000 description 1
- 238000002001 electrophysiology Methods 0.000 description 1
- 230000007831 electrophysiology Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 239000003777 experimental drug Substances 0.000 description 1
- 210000001320 hippocampus Anatomy 0.000 description 1
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Classifications
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- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K15/00—Devices for taming animals, e.g. nose-rings or hobbles; Devices for overturning animals in general; Training or exercising equipment; Covering boxes
- A01K15/02—Training or exercising equipment, e.g. mazes or labyrinths for animals ; Electric shock devices ; Toys specially adapted for animals
- A01K15/027—Exercising equipment, e.g. tread mills, carousels
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- Life Sciences & Earth Sciences (AREA)
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- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Physical Education & Sports Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Zoology (AREA)
- Animal Husbandry (AREA)
- Biodiversity & Conservation Biology (AREA)
- Housing For Livestock And Birds (AREA)
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Abstract
The present invention relates to animal behavior training method and training device.The present invention provides it is a kind of can effectively animal training obtain behavioral memory ability method.This method can be applied to prepare the animal with certain behavioral memory ability, and the animal is, for example, mouse.Present invention also offers the animal training apparatus suitable for the method.
Description
Technical field
The invention belongs to Animal Behavior Science field, more particularly it relates to animal behavior training method and training
Device.
Background technology
In basic research field, experimental animal model is indispensable for the neuromechanism for illustrating behavior.In medicine
Development field has a common recognition：More perfect animal model is very crucial for succeeding in developing for drugs for nervous.People
Generally believe that the disease diagnosing system based on symptom finally needs to be replaced by the new system based on Pathological Physiology；But at present
Understanding for Neurobiology and science of heredity is thorough not enough, therefore cannot support this diagnosis.For cognitive disorder, one
Highly difficult actual conditions are difficult in mouse to differentiate and measure higher cognitive function, to simulate the intelligence of the mankind.And animal
The shortage of model is one of key problem in the drug development of neuropsychological disease, this can solve drug release to a certain extent
The effect of thing the difference on patient and animal model.In other cerebral diseases there are it is same the problem of, such as all nerves
The experimental drug of protectiveness is considered as having medicable in animal model, but all have failed in clinical second phase or three phases,
This clinic conversion in failure strong indication we should reexamine existing animal model and clinical development strategy.Generally recognize
If it is not good animal model, then it is it is difficult to the imagination to make progress on pathophysiological mechanism and developing new drug.
In basic research field, the various means such as light heredity, electro physiology make the neural circuitry research of behavior rise to one
The new stage.In disease research and course of drug development, current most promising mode is to simulate brain by way of interior phenotype
Disease.Interior phenotype be can be measured in disease certain part performance, can regard as than complete disease more based on disease
Sick model of element；In addition to gene level, nervous physiology, biochemistry, neurotomy, cognition or neuropsychological can also be
Index.All symptoms for attempting analog neuron disease (such as schizophrenia) are probably that intelligence, better method are not poly-
The burnt symptom being easier to understand at some or symptom cluster.The technical progress such as nearest behaviouristics, light heredity, imaging in vivo,
Allow researcher to be directed to the whole animal for being carrying out complex behavior, observed with very high spatial and temporal resolution and manipulation is neural
The activity of loop, and allow people studied in Disease background in the relevant neural circuitry of phenotype behavior, so as to fulfill more
Good interior phenotype model.
Before nearest light is hereditary, electrophysiologic study prompting inner side prefrontal cortex (mPFC) is probably interior phenotype one has
The target spot brain area of scape：The research that the laboratory of the present inventor is published in Science shows that the activity of mPFC period of delays is for work
The study of memory tasks is extremely important；In addition the information that is incident upon working memory memory tasks of the hippocampus to inner side prefrontal cortex
The coding phase is necessary；And inner side prefrontal cortex is compressive resistance reacts, it is incident upon in class Depressive behavior and all plays important work
With.
Since working memory is a clear and definite interior phenotype in numerous diseases, working memory is disease research one is probed into
A direction, is developed for this respect.Therefore, the method and apparatus of animal memory behavior research are urgently developed in this area, and obtain
There must be the animal behavior model of corelation behaviour ability.
The content of the invention
It is an object of the invention to provide animal behavior training method and training device.
In the first aspect of the present invention, there is provided a kind of non-matching delay working memory behavior normal form instruction of mouse based on smell
Practice method, the described method includes：
(S1) animal training apparatus is provided, it includes being used for the babinet for accommodating animal, positioned at the snorkel and water of babinet
Pipe；Described water pipe one end connects mobilizable water nozzle, for feeding water to mouse；
(S2) mouse stop drinking-water 50-100 it is small when (when preferably 60-90 is small, when more preferably 65-80 is small) after, be fixed on
Fixing device；
(S3) instruct, including：
(a) water nozzle position is adjusted to initial position, positional distance mouse mouth front 2.5-3.5mm, lower section 2.5-
The position of 3.5mm；
(b) smell 1 is given into babinet by snorkel and continues 1 ± 0.2 second；Stop giving smell 1 afterwards, 2-8 seconds (compared with
Good ground 4-5 seconds) after；Smell 2 is given again continues 1 ± 0.2 second；
(c) water nozzle is proceeded to the mouth of contact mouse, 6 ± 1 microlitres of water outlet；
(d) determine whether mouse licks water；As mouse does not lick water, repeat step (a)~(c)；As mouse licks water, then enter
(S4) process；
(S4) learn, including：
(e) water nozzle is maintained to be in initial position；
(f) smell 1 is given into babinet by snorkel and continues 1 ± 0.2 second；Stop giving smell 1 afterwards, 2-8 seconds (compared with
Good ground 4-5 seconds) after；Smell 2 is given again continues 1 ± 0.2 second；
(g) determine whether mouse licks water；As mouse licks water, 6 ± 1 microlitres of water nozzle water outlet；As mouse does not lick water, meter Miss values
It is 1 time cumulative；Wherein initial Miss values are 0；
(h) determine whether Miss values are more than m；As Miss values are more than m, then it is returned to (S3) step and is instructed；Such as Miss
Value is less than m, then carries out step (i)；
(i) determine to lick water cumulative number, it is such as accumulative to lick water and be not up to n times, then repeat step (e)~(h)；As added up
Lick water to reach n times, then carry out step (j)；
(j) using 24 it is small when counted as one day, calculate and add up this day to lick whether water reaches x times, it is such as accumulative to lick water and reach x times, then
Terminate training in this day；Lick water as accumulative and be not up to x times, be then returned to (S3) step and instructed；
Above operating method carries out 1-10 days (such as 2,3,4,5,7,9 days), so as to obtain with based on the non-matching of smell
Postpone the mouse of working memory behavior normal form.
In a preference of the non-matching delay working memory behavior normal form training method of the mouse based on smell,
In step (b) or step (f), in 2 transfer process of smell 1 and smell, remaining smell is excluded using air interchanger；It is preferred that
The air interchanger is scavenger fan.
It is described in another preference of the non-matching delay working memory behavior normal form training method of the mouse based on smell
Initial position be 3mm, lower section 3mm in front of the mouse mouth position.
In another preference of the non-matching delay working memory behavior normal form training method of the mouse based on smell, m 3
~15 positive integer；Preferably 4~10 positive integer；Or the positive integer that n is 20~40；Preferably 25~35 it is just whole
Number；Or the positive integer that x is 70~150；Preferably 80~120 positive integer.
In another aspect of this invention, there is provided a kind of method that trained mouse licks water, the described method includes：
(s1) animal training apparatus is provided, it includes being used for the babinet for accommodating animal, positioned at the snorkel and water of babinet
Pipe；Described water pipe one end connects mobilizable water nozzle, for feeding water to mouse；
(s2) mouse stop drinking-water 50-100 it is small when (when preferably 60-90 is small, when more preferably 65-80 is small) after, be fixed on
Fixing device；
(s3) water is licked in training, including：
(1) water nozzle position is adjusted to initial position, positional distance mouse mouth front 2.5-3.5mm, lower section 2.5-
3.5mm, makes 10 ± 2 microlitres of water nozzle water outlet；
(2) determine whether mouse licks water；Water is such as licked, carries out step (3)；If do not licked water, water nozzle is set to advance to contact mouse
Mouth, determine if to lick water；As licked water, step (3) is carried out；As still do not licked water, water nozzle is set to be corrected to initial bit
Put, repeat step (1)；
(3) number for licking hydrodynamic(al) work is counted, often occurs 3 times and licks hydrodynamic(al) work, 4 microlitres of water nozzle water outlet；
(4) lick water and add up less than y microlitres or do not lick for continuous 2 seconds water, repeat step (3)；Such as lick water to add up to reach y microlitres, then
Water nozzle is corrected to initial position；
(5) using 24 it is small when counted as one day, calculate and lick water adds up whether to reach z microlitres this day；As add up this day to lick water less than
800 microlitres, then after being delayed 5 ± 1 minutes, repeat step (1)~(4)；Ruo Ben, which adds up to lick water, has reached 800 microlitres,
Then terminate training in this day.
The one side of the method for water is licked in the trained mouse, y is 150~250 positive integer；Preferably 180~
20 positive integer；Or the positive integer that z is 700~900；Preferably 750~850 positive integer.
The another aspect of the method for water is licked in the trained mouse, mobilizable water nozzle is by mobilizable water nozzle system
System control；Mobilizable water nozzle system includes：One motor, a motor screw, several rectangular shaped sliders, and one and square
The water nozzle that shape sliding block is connected.
In another aspect of this invention, there is provided a kind of animal training apparatus, the device include：
Babinet, the side wall of the babinet set the hole being in communication with the outside；
Mouse body fixing device in babinet, head fixing device, it is possible to achieve by mouse be fixed and
Moved in certain position；
Snorkel, it is inserted into babinet, for giving smell during training mouse；The snorkel is with being located at
Being connected to device of air outside babinet；
Water pipe, it is inserted into babinet；The babinet external port of water pipe is connected with the waterworks outside babinet；
Mobilizable water nozzle system in babinet, it is connected with the babinet inner port of water pipe.
In a preference, mobilizable water nozzle system includes：Motor；It is connected with motor and is driven by motor
Motor screw；2~5 rectangular shaped sliders, it can be driven by motor screw and displacement of weighing occurs；The water being connected with rectangular shaped slider
Mouth, the water nozzle are connected with the babinet inner port of water pipe.
In another preference, air exchange system is also set up on the babinet of the animal training apparatus, can be by babinet
Smell discharges babinet；It is preferred that the air exchange system is scavenger fan.
The other side of the present invention is apparent to those skilled in the art due to this disclosure
's.
Brief description of the drawings
The schematic diagram of Fig. 1, mouse training device.
Fig. 2, mechanical water nozzle schematic diagram.
The schematic diagram of the displacement of relative position occurs for Fig. 3, water nozzle and animal.Left figure, water nozzle 8 is apart from animal during autonomous learning
About 5 millimeters of the mouth of (mouse) 12；Right figure, water nozzle 8 is close to 12 mouth of animal and automatic outletting when water is licked in religion.
Fig. 4, the training mouse of embodiment 3 lick the flow diagram of water.
The schematic diagram that Fig. 5, the smell conversion method of embodiment 4 and mouse reaction are judged.
Fig. 6, embodiment 4 the mouse working memory behavior based on smell training schematic diagram.
Fig. 7, embodiment 4 the mouse working memory behavior based on smell training result.
Embodiment
The behavior model of animal is all significant for the medicament research and development based on interior phenotype and basic scientific research.The present inventor
By in-depth study, there is provided it is a kind of can effectively animal training obtain behavioral memory ability method.This method can be applied
In preparing the animal with certain behavioral memory ability, the animal is, for example, mouse.
Since working memory is a clear and definite interior phenotype in numerous diseases, the present inventor is directed to working memory, exploitation
High throughput full automatic mouse cognitive behavior training platform.
Working memory is important cognitive function, its neuromechanism is important unknown problem.Working memory is in spirit point
Split defective in the patients such as disease, alzheimer's disease, apoplexy, therefore the animal model of working memory can be as these diseases
Interior phenotype, and the model of drug verification is provided for disease research.This method on the basis of training system hardware components are automated,
The automatic training of mouse working memory behavior is realized, the flow in automatic training is optimized, can reach mouse in three days
To more than 80% behavior accuracy, realized that the complete of behavior is learned in one week.With reference to automation training system hardware components
With the design of blind experiment, this method can minimize the human interference of behavior outcome, and be designed by high throughput quickly to obtain
Take behavioral data.This method is to illustrating the neuromechanism of working memory, research and development cerebral disease medicine is of great significance.
Present invention also offers a kind of animal training apparatus, which includes：Babinet, the side wall of the babinet are set and the external world
The hole of connection；Mouse body fixing device in babinet, head fixing device, it is possible to achieve mouse is fixed simultaneously
Moved in certain position；Snorkel, it is inserted into babinet, for giving smell during training mouse；This is logical
Tracheae and being connected to device of air outside babinet；Water pipe, it is inserted into babinet；The babinet external port of water pipe is with being located at babinet
Outer waterworks connection；Mobilizable water nozzle system in babinet, it is connected with the babinet inner port of water pipe.
The animal training apparatus can be manual operation；It is preferred that automation control system can also be set
Manipulate snorkel, water pipe, to device of air, air-breather, needed according to operation at the appointed time, needed for the position specified carries out
Operation, so as to avoid manual operation may caused by error, there is provided more accurately operator scheme.
As the preferred embodiment of the present invention, mobilizable water nozzle system includes：Motor；It is connected with motor and by electricity
The motor screw of machine driving；2~5 rectangular shaped sliders, it can be driven by motor screw and displacement of weighing occurs；It is connected with rectangular shaped slider
Dynamic water nozzle, the water nozzle are connected with the babinet inner port of water pipe.The design can accurately manipulate water nozzle feedwater distance and to
Water time point.
As the preferred embodiment of the present invention, air exchange system is also set up on the babinet, the smell in babinet can be discharged
Babinet；It is preferred that the air exchange system is scavenger fan.
With reference to specific embodiment, the present invention is further explained.It is to be understood that these embodiments are merely to illustrate the present invention
Rather than limit the scope of the invention.The experimental method of actual conditions is not specified in the following example, usually according to conventional strip
Part, or according to the condition proposed by manufacturer.
Embodiment 1, animal training apparatus
Such as Fig. 1, in the present embodiment, prepare an animal training apparatus for being suitable for training mouse.The training device
Including：
Babinet 1, the side wall of the babinet set the hole being in communication with the outside；And scavenger fan 6 is set, for by babinet
Exhaust gas exclude.
In babinet, mouse body fixing device 71 and head fixing device 72 are set, it is possible to achieve mouse is fixed
And moved in certain position.The body restraints 71 can move back and forth or left and right in certain amplitude.
Snorkel 2 is set to be inserted into babinet, for giving smell during training mouse, observation mouse is anti-
Should.The snorkel and being connected to device of air 4 outside babinet.
Water pipe 3 is set to be inserted into babinet, the babinet interior conduit of water pipe connects mobilizable water nozzle system；The babinet of water pipe
External port is connected with the waterworks 5 outside babinet.
Schematic diagram such as Fig. 2 of the movable water nozzle system.The system includes a motor 10, a motor screw 9,
Several rectangular shaped sliders 11, and a water nozzle 8 being connected with rectangular shaped slider.The babinet interior conduit of the water nozzle and water pipe 3 connects
It is logical.
By the combination of mechanical structure, motor can be driven the cunning changed into before and after rectangular shaped slider of motor screw
Dynamic, linkage water nozzle moves accordingly.Such as Fig. 3, water nozzle 8 and the mouth of animal 12, can occur certain displacement.
Embodiment 2, automation animal training apparatus
As embodiment 1 makes animal training apparatus, snorkel, water nozzle system and the control module company of the animal training apparatus
Connect, be allowed to automatically switch under program, obtain the animal training apparatus of automation, in order to automate training.
The control module is provided with control snorkel and gives gas, the program of gas rotation, and is provided with control
Movable water nozzle back-and-forth motion, left-right rotation, the program given water or do not give water.
The method that embodiment 3, training mouse association lick water
The purpose reached needed for this method is：Overcome the mouse that head is fixed to fear Behavioral training system and experimenter
Fear, association, which licks, licks water nozzle to be rewarded (distilled water).Final purpose is that experimenter can be obtained from licking in water behavior for mouse
Obtain the feedback information of mouse study situation.
Training mouse licks water process such as Fig. 4.
The first step, starts, allows animal familiarization training system
Behavioral training pipe is shifted to an earlier date into half a day it is put into mouse cage and allows mouse independently to explore and familiarization training environment.
Second step, mouse is fixed by way of fixing head sheet metal and adjusts the relative position of mouse and water nozzle
Mouse after when taking stopping drinking-water 72 small, body restraints mouse body being leniently fixed in babinet 1
71, and fix mouse head using head fixing device 72.
Pass through mobile mouse and the relative position of water nozzle 8.The final position of adjustment is that water nozzle 8 is located at 3 in front of mouse mouth
(it is known as initial position) at millimeter, 3 millimeters of lower section.Water nozzle is too near on the one hand flase drop that mouse mouth can cause to lick hydrodynamic(al) work
Survey, mouse on the other hand can be caused nervous caused by it can not complete cleaning behavior with fore paw and struggled；Water nozzle is too far then
Detection sensitivity can be caused to decline.
3rd step, is trained and licks water
The training process of water is licked in training：
(1) water nozzle position is adjusted to initial position, positional distance mouse mouth front about 3mm, lower section about 3mm.Make water
About 10 microlitres of mouth water outlet.
(2) determine whether mouse licks water.Water is such as licked, carries out step (3).If do not licked water, water nozzle is set to advance to contact mouse
Mouth, determine if to lick water；As licked water, step (3) is carried out；As still do not licked water, water nozzle is set to be corrected to initial bit
Put, repeat step (1).
(3) number for licking hydrodynamic(al) work is counted, often occurs to lick hydrodynamic(al) 3 times and gives a water, is i.e. often generation licks hydrodynamic(al) 3 times
Make, 4 microlitres of water nozzle water outlet.Be so designed that, can to avoid water frequency very fast (8 hertz of highest) is licked because of mouse caused by go out every time
Water mouse has little time to swallow down, water droplet is accumulated on water nozzle, and water detection is licked in influence.
(4) lick water and add up less than 200 microlitres or do not lick for continuous 2 seconds water, repeat step (3)；Such as licking water, to add up full 200 micro-
Rise, then water nozzle is corrected to initial position.
(5) using 24 it is small when counted as one day, calculate and lick water adds up whether to reach 800 microlitres this day；As added up to lick water this day not
It is 800 microlitres full, then it is delayed after five minutes, repeats step (1~4)；Ruo Ben, which adds up to lick water, has reached 800 microlitres, then ties
Shu Ben is trained.
Above example, simulates manual type with waterworks, allows mouse association to associate the forward motion of water outlet and motor,
But the appearance of the two be not completely it is associated (step (3) embody it is this endless fully associative, be not motor advance just meeting
Water outlet, only in the case where first water outlet 10ul does not lick, motor can just advance), avoid mouse from being formed to motor forward motion
Dependence.
The above method altogether perform 3 days, it turns out that, all mouse can not advance in motor and (not instruct) in the case of from
Water 800ul (daily) is licked in main completion.
The non-matching delay working memory behavior normal form training method of embodiment 4, a kind of mouse based on smell
The design of mouse working memory behavior based on smell is as shown in figure 5, mouse needs be spaced former and later two
Smell (smell 1, smell 2) is licked when mismatching and licks water nozzle to be rewarded；If licking water nozzle conversely, being licked when two smells match,
It cannot then be rewarded；The reward given is to give 6uL water.
Mouse behavior automation training method based on smell includes four steps：Cut off the water supply, water is licked in training, and training is in two differences
Water, autonomous learning are licked after smell.
The automation training method that water is licked in training and two steps of water are licked in training after two different odors is described below.
This method training mouse overcomes the fear to smell, can independently be licked after two different odors occur successively
Water.The step has automated defined in training program two kinds of training process (trail), is teaching (teach, Fig. 6 respectively
The left-half of flow chart) and study (right half part of learn, Fig. 6 flow chart).Specific training process is as follows：
The first step, starts, allows animal familiarization training system
Behavioral training pipe is shifted to an earlier date into half a day it is put into mouse cage and allows mouse independently to explore and familiarization training environment.
Second step, take stop drinking-water 72 it is small when after mouse, the body that mouse body is leniently fixed in babinet 1 consolidates
Determine device 71, and mouse head is fixed using head fixing device 72.
Pass through mobile mouse and the relative position of water nozzle 8.The final position of adjustment is that water nozzle 8 is located in front of mouse mouth
About 3 millimeters, (be known as " initial position ") at about 3 millimeters of lower section.On the one hand water nozzle, which is too near to mouse mouth, can cause to lick hydrodynamic(al) work
Error detection, mouse on the other hand can be caused nervous caused by fore paw can not be used to complete cleaning behavior and struggled；Water nozzle
Far can then detection sensitivity be caused to decline very much.
3rd step, is trained
A, (teach) is instructed
(a) water nozzle position is adjusted to initial position, positional distance mouse mouth front about 3 millimeters, about 3 millimeters of lower section
Place.
(b) scavenger fan is opened in babinet, it is for 1 seconds that smell 1 is given into babinet by snorkel；Stop afterwards to
Smell Isosorbide-5-Nitrae is given after -5 seconds；It is for 1 seconds that smell 2 is given again.
(c) water nozzle is proceeded to the mouth of contact mouse, 6 microlitres of water outlet.
(d) determine whether mouse licks water；As mouse does not lick water, repeat step (a)~(c)；As mouse licks water, then under entering
One link, i.e., following B processes.
B, (learn) is learnt
(e) water nozzle is in initial position.
(f) scavenger fan is opened in babinet, it is for 1 seconds that smell 1 is given into babinet by snorkel；Stop afterwards to
Smell Isosorbide-5-Nitrae is given after -5 seconds；It is for 1 seconds that smell 2 is given again.
(g) determine whether mouse licks water；As mouse licks water, 6 microlitres of water nozzle water outlet；As mouse does not lick water, meter Miss values are tired out
Add 1 time (initial Miss values are 0).
(h) determine whether Miss values are more than 5；As Miss values be more than 5, then be returned to " A, teaching " step and instructed；Such as
Miss values are less than 5, then carry out step (i).
(i) determine to lick water cumulative number, it is such as accumulative to lick water and be not up to 30 times, then repeat step (e)~(h)；As tired out
Meter is licked water and is reached 30 times, then carries out step (j)；
(j) using 24 it is small when counted as one day, calculate and add up to lick whether water reaches 100 (always licking containing teaching and study this day
Waterside number), it is such as accumulative to lick water and reach 100 times, then terminate training in this day；Lick water as accumulative and be not up to 100 times, then be returned to " A,
Teaching " step is instructed, and to retain the weak dependence that motor advances with water outlet, can be easier to lick when so daily starting
Water.
The behavior outcome such as Fig. 7 trained using the system and method.The figure shows that 9 mouse pass through the training system
After the training of 6 days, in the follow-up situation of 5 days.
The picture left above of Fig. 7 showed mouse after the training system training of 6 days, in (training daily in follow-up 5 days
120 trial) training accuracy.Its result is presented, and in follow-up 5 days, average accuracy increases significantly.
The top right plot of Fig. 7 shows mouse after the training system training of 6 days, the mouse in training in follow-up 5 days
The ratio (can be licked by licking to lick to be awarded but do not licked) of miss trial.It is the results show that the miss trial in 5 days
Ratio it is very low.
The lower-left figure of Fig. 7 show false alarm (FA) trial ratio (even if lick lick also without award but according to
So lick and lick)., the results show that with the increase of training number of days, violating the type error rate gradually reduces for it.
The bottom-right graph of Fig. 7 shows that the ratio of correct rejection (CR) trial (licks and licks and will not be awarded
Do not lick and lick at the same time).It is the results show that with the increase of training number of days, the type ratio is gradually increasing.
The above results are as it can be seen that 9 mouse can independently be learned after the training system training of 6 days at follow-up 5 days
Postpone the behavior normal form of non-matching working memory.The method of the present invention has exploitativeness, and reproducibility.
All references mentioned in the present invention is incorporated herein by reference, independent just as each document
It is incorporated as with reference to such.In addition, it should also be understood that, after reading the above teachings of the present invention, those skilled in the art can
To be made various changes or modifications to the present invention, such equivalent forms equally fall within the model that the application the appended claims are limited
Enclose.
Claims (10)
- A kind of 1. non-matching delay working memory behavior normal form training method of mouse based on smell, it is characterised in that the side Method includes：(S1) animal training apparatus is provided, it includes being used for the babinet for accommodating animal, positioned at the snorkel and water pipe of babinet；Institute State water pipe one end and connect mobilizable water nozzle, for feeding water to mouse；(S2) after when mouse stopping drinking-water 50-100 is small, it is fixed on fixing device；(S3) instruct, including：(a) adjust water nozzle position and arrive initial position, positional distance mouse mouth front 2.5-3.5mm, lower section 2.5-3.5mm Position；(b) smell 1 is given into babinet by snorkel and continues 1 ± 0.2 second；Stop giving smell 1 afterwards, after 2-8 seconds；Give again Smell 2 is given to continue 1 ± 0.2 second；(c) water nozzle is proceeded to the mouth of contact mouse, 6 ± 1 microlitres of water outlet；(d) determine whether mouse licks water；As mouse does not lick water, repeat step (a)~(c)；As mouse licks water, then enter (S4) mistake Journey；(S4) learn, including：(e) water nozzle is maintained to be in initial position；(f) smell 1 is given into babinet by snorkel and continues 1 ± 0.2 second；Stop giving smell 1 afterwards, after 2-8 seconds；Give again Smell 2 is given to continue 1 ± 0.2 second；(g) determine whether mouse licks water；As mouse licks water, 6 ± 1 microlitres of water nozzle water outlet；As mouse does not lick water, meter Miss values add up 1 time；Wherein initial Miss values are 0；(h) determine whether Miss values are more than m；As Miss values are more than m, then it is returned to (S3) step and is instructed；As Miss values are small In m, then step (i) is carried out；(i) determine to lick water cumulative number, it is such as accumulative to lick water and be not up to n times, then repeat step (e)~(h)；Water is licked as accumulative Reach n times, then carry out step (j)；(j) using 24 it is small when counted as one day, calculate and add up this day to lick whether water reaches x times, it is such as accumulative to lick water and reach x times, then terminate This day trains；Lick water as accumulative and be not up to x times, be then returned to (S3) step and instructed；Above operating method carries out 1-10 days, so as to obtain with the non-matching delay working memory behavior normal form based on smell Mouse.
- 2. the method as described in claim 1, it is characterised in that in step (b) or step (f), smell 1 and smell 2 are converted Cheng Zhong, remaining smell is excluded using air interchanger；It is preferred that the air interchanger is scavenger fan.
- 3. the method as described in claim 1, it is characterised in that the initial position be in front of the mouse mouth 3mm, under The position of square 3mm.
- 4. the method as described in claim 1, it is characterised in that m is 3~15 positive integer；Preferably 4~10 it is just whole Number；OrN is 20~40 positive integer；Preferably 25~35 positive integer；OrX is 70~150 positive integer；Preferably 80~120 positive integer.
- 5. a kind of method that trained mouse licks water, it is characterised in that the described method includes：(s1) animal training apparatus is provided, it includes being used for the babinet for accommodating animal, positioned at the snorkel and water pipe of babinet；Institute State water pipe one end and connect mobilizable water nozzle, for feeding water to mouse；(s2) after when mouse stopping drinking-water 50-100 is small, it is fixed on fixing device；(s3) water is licked in training, including：(1) adjust water nozzle position arrive initial position, the positional distance mouse mouth front 2.5-3.5mm, lower section 2.5-3.5mm, Make 10 ± 2 microlitres of water nozzle water outlet；(2) determine whether mouse licks water；Water is such as licked, carries out step (3)；If do not licked water, water nozzle is set to advance to the mouth of contact mouse Portion, determines if to lick water；As licked water, step (3) is carried out；As still do not licked water, water nozzle is set to be corrected to initial position, weight Step (1) is carried out again；(3) number for licking hydrodynamic(al) work is counted, often occurs 3 times and licks hydrodynamic(al) work, 4 microlitres of water nozzle water outlet；(4) lick water and add up less than y microlitres or do not lick for continuous 2 seconds water, repeat step (3)；Such as lick water to add up to reach y microlitres, then water nozzle It is corrected to initial position；(5) using 24 it is small when counted as one day, calculate and lick water adds up whether to reach z microlitres this day；It is as micro- less than 800 in added up this day to lick water Rise, then after being delayed 5 ± 1 minutes, repeat step (1)~(4)；Ruo Ben, which adds up to lick water, has reached 800 microlitres, then terminates This day trains.
- 6. method as claimed in claim 5, it is characterised in that y is 150~250 positive integer；Preferably 180~20 Positive integer；OrZ is 700~900 positive integer；Preferably 750~850 positive integer.
- 7. the method as described in claim 1 or 5, it is characterised in that mobilizable water nozzle is by mobilizable water nozzle system System control；Mobilizable water nozzle system includes：One motor, a motor screw, several rectangular shaped sliders, and one and square The water nozzle that shape sliding block is connected.
- 8. a kind of animal training apparatus, it is characterised in that the device includes：Babinet, the side wall of the babinet set the hole being in communication with the outside；Mouse body fixing device in babinet, head fixing device, it is possible to achieve mouse is fixed and certain Moved in position；Snorkel, it is inserted into babinet, for giving smell during training mouse；The snorkel is with being located at babinet Outer connects to device of air；Water pipe, it is inserted into babinet；The babinet external port of water pipe is connected with the waterworks outside babinet；Mobilizable water nozzle system in babinet, it is connected with the babinet inner port of water pipe.
- 9. animal training apparatus as claimed in claim 8, it is characterised in that mobilizable water nozzle system includes：Motor；It is connected with motor and by motor-driven motor screw；2~5 rectangular shaped sliders, it can be driven by motor screw and displacement of weighing occurs；The water nozzle being connected with rectangular shaped slider, the water nozzle are connected with the babinet inner port of water pipe.
- 10. animal training apparatus as claimed in claim 8, it is characterised in that air exchange system is also set up on the babinet, can Smell in babinet is discharged into babinet；It is preferred that the air exchange system is scavenger fan.
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| CN108633771A (en) * | 2018-05-17 | 2018-10-12 | 郑州大学 | Learning training system is synchronized for animal population brain electricity |
| CN109907000A (en) * | 2019-03-12 | 2019-06-21 | 山西中医药大学 | Prepare the device and method of animal models of depression |
| CN110786261A (en) * | 2018-08-03 | 2020-02-14 | 中国科学院上海生命科学研究院 | Mouse behavior training device and training method thereof |
| CN111685057A (en) * | 2020-07-14 | 2020-09-22 | 北京大学第六医院 | Device and method for training and testing working memory capacity of rodent |
| CN113392975A (en) * | 2021-07-07 | 2021-09-14 | 温州医科大学 | Construction method of delay reward benefit and fraud trade-off decision-making behavioural model |
| CN113973744A (en) * | 2021-10-15 | 2022-01-28 | 浙江大学 | Autonomous in-cage behavior training device and method for small animals |
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| CN108633771B (en) * | 2018-05-17 | 2021-01-26 | 郑州大学 | Electroencephalogram synchronous learning training system for animal groups |
| CN110786261A (en) * | 2018-08-03 | 2020-02-14 | 中国科学院上海生命科学研究院 | Mouse behavior training device and training method thereof |
| CN109907000A (en) * | 2019-03-12 | 2019-06-21 | 山西中医药大学 | Prepare the device and method of animal models of depression |
| CN111685057A (en) * | 2020-07-14 | 2020-09-22 | 北京大学第六医院 | Device and method for training and testing working memory capacity of rodent |
| CN113392975A (en) * | 2021-07-07 | 2021-09-14 | 温州医科大学 | Construction method of delay reward benefit and fraud trade-off decision-making behavioural model |
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| CN113973744A (en) * | 2021-10-15 | 2022-01-28 | 浙江大学 | Autonomous in-cage behavior training device and method for small animals |
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