CN111685049A

CN111685049A - Space working memory behavior training device and training method

Info

Publication number: CN111685049A
Application number: CN201910185673.1A
Authority: CN
Inventors: 李澄宇; 邹诗敏
Original assignee: Center for Excellence in Brain Science and Intelligence Technology Chinese Academy of Sciences
Current assignee: Center for Excellence in Brain Science and Intelligence Technology Chinese Academy of Sciences
Priority date: 2019-03-12
Filing date: 2019-03-12
Publication date: 2020-09-22
Anticipated expiration: 2039-03-12
Also published as: WO2020182107A1; CN111685049B

Abstract

The invention aims to provide a space working memory behavior training device which can be used for evaluating the space working memory capability of a mouse, reducing human interference factors to the maximum extent and acquiring stable training behavior data efficiently and massively. Another objective of the present invention is to provide a spatial working memory behavior training method, which includes the above spatial working memory behavior training device. The space working memory behavior training device comprises a central area, a starting arm, a plurality of alternative arms, a door body, a detection assembly, a feeding assembly, a first driving unit, a second driving unit and a control unit. The control unit controls the starting and stopping of the feeding assembly, the first driving unit and the second driving unit according to the output signal of the detection assembly.

Description

Space working memory behavior training device and training method

Technical Field

The invention relates to a space working memory behavior training device and a training method.

Background

Working memory is a core cognitive function that involves the storage and processing of information in a short period of time. The working memory is considered to be positively correlated with the learning ability of children and teenagers and is also an important evaluation index in intelligence test; many psychiatric disorders have symptoms of decline in working memory, such as depression, schizophrenia, alzheimer's disease, and parkinson's disease, among others.

In the field of basic research, cognitive functions are complex, working memory is one of important functions, can be scientifically and quantitatively measured, and is an entry point for researching complex cognitive functions. In the field of disease research and drug development with higher application value, the method for simulating all symptoms of neurological diseases (such as Alzheimer's disease) is difficult to realize, and the method with higher feasibility is to select core symptoms which are easier to understand as entry points and construct a disease model by simulating the core symptoms. The elucidation of the neural circuit mechanism of working memory has important significance for understanding the cognitive function under physiological conditions, and also has a promoting effect on further understanding the pathological mechanism of diseases and developing new drugs. For the mechanism research of cognitive function, a practical obstacle is how to establish a suitable animal model to identify and measure the advanced cognitive function, and the same problem exists in the fields of brain disease research and new drug development.

The spatial working memory behavior training task is a better entry point for the above obstacles. On one hand, the working memory based on spatial position sensation is very important for daily life of human beings, and the early symptoms of some mental diseases (such as Alzheimer's disease) are just the spatial working memory decline, so that the research on the spatial working memory has clinical value. On the other hand, the mouse is an ideal model animal due to the advantages of multiple transgenic strains and mature optogenetic and calcium imaging technologies; the spatial position sense is just the dominant sense of the mouse; by combining the characteristics, the feasibility and the research value are achieved for training the mouse to perform the spatial working memory behavior task.

Based on this, there is a need for a training device and a training method for evaluating the spatial working memory of mice.

Disclosure of Invention

The invention aims to provide a space working memory behavior training device which can be used for evaluating the space working memory capability of a mouse, reducing human interference factors to the maximum extent and acquiring stable training behavior data efficiently and massively.

Another objective of the present invention is to provide a spatial working memory behavior training method, which includes the above spatial working memory behavior training device.

To achieve the foregoing object, a spatial working memory behavior training device includes:

the device body is a semi-open box body comprising a bottom wall of the body and a side wall of the body, the box body comprises a central area, a starting arm and a plurality of alternative arms, the starting arm and the alternative arms surround the central area and are respectively communicated with the central area, and the bottom wall of the central area is provided with a rotatable turntable;

the door bodies are respectively arranged at the positions, close to the central area, of the starting arm and the alternative arm;

the detection assemblies are respectively arranged in the starting arm and the alternative arm and at positions far away from the central area relative to the door body and used for detecting whether a mouse passes through the central area or not;

the feeding assembly is respectively communicated with the inner spaces of the starting arm and the standby arm and is used for feeding food required by the mouse;

the first driving unit is connected with the rotary table and drives the rotary table to rotate;

the second driving unit is connected with the door body and drives the door body to open and close the starting arm or the alternative arm; and

and the control unit is respectively connected with the first driving unit, the second driving unit, the detection assembly and the feeding assembly and controls the starting and stopping of the feeding assembly, the first driving unit and the second driving unit according to an output signal of the detection assembly.

In one or more embodiments, the detection assembly is disposed on the body sidewall in the initial arm and the alternate arm corresponding to a height of the mouse.

In one or more embodiments, the detection assembly includes a transmitting unit and a receiving unit, which are respectively disposed on the body side walls on both sides of the initial arm and both sides of the alternative arm;

wherein the transmitting unit and the receiving unit are arranged at the same height.

In one or more embodiments, the feeding assembly is a water supply assembly, the water supply assembly includes a water source unit, a pump body, and a water inlet pipe, the water inlet pipe penetrates into the training device from the body side wall of the starting arm top and the alternative arm top corresponding to the height of the mouse.

In one or more embodiments, the body bottom plate has an outer extension section disposed outside an outer circumferential side of the starting arm and the alternative arm, and the outer extension section is opened with a mounting hole for receiving the water source unit.

In one or more embodiments, the first driving unit and the second driving unit are steering engines, and swing arms of the steering engines are respectively connected with the door body and the turntable.

To achieve the above object, a method for spatial working memory behavior training is provided, which employs a spatial working memory behavior training apparatus as described above,

the space working memory behavior training method comprises pre-training and formal training, wherein the pre-training and the formal training respectively comprise a plurality of trial times, and each trial time comprises a sample period, a delay period, a selection period and trial time intervals which are sequentially executed; in the sample period, the candidate arm entered by the mouse is defined as a matching arm, and the other candidate arms are defined as non-matching arms;

for the pre-training or formal training:

a sample period, wherein the starting arm and one of the alternative arms are opened, and food is supplied to a matching arm when the mouse is detected to enter the matching arm;

a delay period after the sample period ends, when it is detected that the mouse enters the start arm, the start arm is closed and food is supplied into the start arm, and then the matching arm and one non-matching arm are opened and the mouse is confined in the start arm for a period of time;

a trial interval, after the selection period is finished, when the mouse is detected to enter the starting arm, closing the starting arm and all the alternative arms, and feeding food into the starting arm, wherein one trial is finished, and the mouse waits for the next trial training in the starting arm;

during the pre-training selection period, opening the initial arm, allowing the mouse to enter any one of the alternative arms, when the mouse entry is detected, feeding food into the matched arm or the unmatched arm that the mouse enters, and closing the alternative arm that the mouse does not enter;

in the selection period of the formal training, opening the starting arm, allowing the mouse to enter a matching arm or a non-matching arm, and when the mouse is detected to enter the matching arm, regarding the mouse to return to an error state, not providing food, and waiting for the mouse to return to the starting arm to end the selection period; when it is detected that the mouse enters the unmatched arm, "correct" is returned, food is fed to the unmatched arm, and the mated arm is closed.

In one or more embodiments, during the delay period, the turntable is rotated by any angle after the start arm is closed.

In one or more embodiments, prior to pre-training, the method further comprises an adaptation period, opening the starting arm and all of the alternate arms, allowing the mouse to explore freely in the training apparatus.

In one or more embodiments, the method further comprises the step of stopping or limiting food access by the mouse prior to the acclimation period to maintain the mouse's need for food.

In one or more embodiments, the latency of the delay period is 5 to 90 seconds.

In one or more embodiments, the number of trials n is between 10 and 80 or between 40 and 60.

In one or more embodiments, the length of the wait time of the trial pause is greater than 10 seconds, or 2 times the length of the wait time of the delay period.

The invention has the beneficial effects that:

the spatial working memory behavior training device and the spatial working memory behavior training method are used for monitoring and testing the workpiece behaviors of the mouse, so that the influence of human factors on an experiment can be reduced, and the characteristic that the working memory is declined along with the time extension can be simulated.

Drawings

The above and other features, properties and advantages of the present invention will become more apparent from the following description of the embodiments with reference to the accompanying drawings, in which:

FIG. 1 is a schematic top view of one embodiment of a spatial working memory behavior training apparatus;

FIG. 2 is a schematic bottom view of an embodiment of a spatial working memory behavior training device;

FIG. 3 is a schematic top view of one embodiment of a device body;

FIG. 4 is a schematic perspective view of one embodiment of a device body;

FIGS. 5-6 respectively show schematic views of a detection assembly;

FIG. 7 illustrates a partial, enlarged schematic view of one embodiment of an exercise device;

FIG. 8 shows a schematic cross-sectional view of an embodiment of the second drive unit;

FIG. 9 shows a flow chart of a training method;

fig. 10A to 10C show schematic diagrams of mice in the sample phase, delay phase and selection phase, respectively, in pre-training;

FIG. 11 shows a detailed flow chart of formal training;

fig. 12A to 12C show schematic diagrams of mice in the sample phase, delay phase and selection phase, respectively, in formal training;

FIG. 13 illustrates the results of a performance using a training apparatus and a training method;

figure 14 shows the accuracy of mice under different length of the lag phase conditions.

Detailed Description

The following discloses many different embodiments or examples for implementing the subject technology described. Specific examples of components and arrangements are described below to simplify the present disclosure, but these are merely examples and are not intended to limit the scope of the present disclosure. For example, if a first feature is formed over or on a second feature described later in the specification, this may include embodiments in which the first and second features are formed in direct contact, and may also include embodiments in which additional features are formed between the first and second features, such that the first and second features may not be in direct contact. Additionally, reference numerals and/or letters may be repeated among the various examples throughout this disclosure. This repetition is for the purpose of simplicity and clarity and does not in itself dictate a relationship between the various embodiments and/or configurations discussed. Further, when a first element is described as being coupled or coupled to a second element, the description includes embodiments in which the first and second elements are directly coupled or coupled to each other, as well as embodiments in which one or more additional intervening elements are added to indirectly couple or couple the first and second elements to each other.

It should be noted that, where used, the following description of upper, lower, left, right, front, rear, top, bottom, positive, negative, clockwise, and counterclockwise are used for convenience only and do not imply any particular fixed orientation. In fact, they are used to reflect the relative position and/or orientation between the various parts of the object.

The spatial working memory behavior training device is used for training and recording the spatial working memory behavior of the animal so as to obtain accurate behavioural data. Fig. 1 and 2 show schematic top and bottom views, respectively, of an embodiment of a spatial working memory behavior training apparatus. The training device comprises a device body 1, a door body 2, a detection assembly 3, a feeding assembly 4, a first driving unit 5, a second driving unit 6 and a control unit (not shown in the figure).

Fig. 3 and 4 show a schematic plan view and a schematic perspective view of an embodiment of the apparatus body 1, respectively. Wherein the device body 1 is a semi-open box enclosed by a body bottom wall 10 and a body side wall 11, comprising an initial arm 12, an alternative arm 13 and a central area 140. Wherein, the starting arm 12 has a starting space 120 for accommodating the experimental mouse therein, and the alternative arm 13 is provided in a plurality, and the number thereof may be 4 as shown in the figure, or may be any number larger than two. Within the alternative arm 13 there is also an alternative space 130 allowing to accommodate the laboratory mouse. The central region 140 communicates with the initial space 120 and the optional space 130, respectively, so that a space surrounded by the body side wall 11 and in which the experimental mouse can move is formed in the apparatus body 1. As can be seen from the top view of fig. 4, a circular rotary plate 14 is further embedded in the bottom wall 10 of the body, and the rotary plate 14 is disposed below the central region 140 and is rotatably connected to the bottom wall 10 of the body. Specifically, the rotary disk 14 and the bottom wall 10 of the body may be rotatable by providing a locking groove or a protrusion on the outer periphery of the rotary disk 14 to match with a corresponding groove or protrusion on the inner periphery of the bottom wall 10 of the body.

With continued reference to fig. 1-2, other components of the exercise device are described below. The door body 2 is provided in each of the start arm 12 and the alternate arm 13, respectively, and the door body 2 is provided at a position near the central region 140, and has an open state and a closed state. When the door body 2 is in a closed state, the door body will close the initial space 120 or the alternative space 130 in the initial arm 12 or the alternative arm 13, so that the closed initial space 120 or the alternative space 130 is not communicated with the central area 140, and when the door body 2 is in an open state, the door body will cling to the side wall 11 of the body, so that the initial space 120 or the alternative space 130 is communicated with the central area 140, thereby opening and closing the initial space 120 and the alternative space 130.

The detection assembly 3 is respectively arranged in each initial arm 12 and each alternative arm 13, the position of the detection assembly 3 is arranged in the position far away from the central area 140 in each initial arm 12 and each alternative arm 13 relative to the door body 2, the detection assembly 3 has a detection area, and when a mouse passes through the detection area of the detection assembly 3, the detection assembly 3 can send a signal, so that the function of detecting whether the mouse passes through is achieved.

The feeding assembly 4 is connected to each of the initial space 120 and the alternative space 130, and is capable of feeding food to the initial space 120 or the alternative space 130, wherein the food may include any solid or liquid material required by the mouse, including food, beverage, water, and other food for supplying the mouse, or a combination thereof. In one embodiment, the supply assembly 4 is a water supply assembly capable of supplying water to the interior of the apparatus, and in the various embodiments of the present application, the supply assembly 4 is described as a water supply assembly.

The first driving unit 5 is connected with the rotary disc 14, and when the first driving unit 5 enters the working state, the rotary disc 14 can be driven to rotate at any angle on the inner circumference of the bottom wall 10 of the body. The second driving unit 6 is connected with the door body 2, and when the second driving unit 6 enters a working state, the door body 2 can be driven to switch between an open state and a closed state.

The control unit is connected to the first driving unit 5, the second driving unit 6, the detecting assembly 3 and the feeding assembly 4, respectively, and commands the feeding assembly 4, the first driving unit 5 and the second driving unit 6 to enter the working state or stop according to the output signal of the detecting assembly 3. The control unit may include one or more hardware processors, such as one or more combinations of microcontrollers, microprocessors (e.g., MCU chips or 51 singlechips), Reduced Instruction Set Computers (RISC), Application Specific Integrated Circuits (ASICs), application specific instruction integrated processors (ASIPs), Central Processing Units (CPUs), Graphics Processing Units (GPUs), Physical Processing Units (PPUs), microcontroller units, Digital Signal Processors (DSPs), Field Programmable Gate Arrays (FPGAs), Advanced RISC Machines (ARMs), Programmable Logic Devices (PLDs), any circuit or processor capable of performing one or more functions, and the like. The specific control strategy of the control unit will be described in detail later.

Although one embodiment of the spatial working memory behavior training apparatus is described above, in other embodiments of the training apparatus, other components such as the apparatus body and the detection assembly may have more details in many respects than the above-described embodiments, and at least a portion of the details may have various variations. At least some of these details and variations are described below in several embodiments.

Fig. 5 and 6 show schematic views of an embodiment of the detection assembly, and fig. 7 shows an enlarged partial schematic view of an embodiment of the training device, respectively. Referring to fig. 1 to 7, the detecting assembly 3 includes a transmitting unit 31 and a receiving unit 32, the transmitting unit 31 and the receiving unit 32 are respectively disposed on the body side walls 11 on both sides of the starting arm 12 and the alternative arm 13, and meanwhile, the transmitting unit 31 and the receiving unit 32 have the same horizontal height, which is set corresponding to the height of the mouse in the training device, so as to facilitate detecting whether the mouse passes through. In one embodiment, the horizontal heights of the transmitting unit 31 and the receiving unit 32 are set to be 2 cm above the bottom wall 10 of the body, so that whether the mouse passes or not can be conveniently detected. In one embodiment, the detecting assembly 3 is an infrared detecting device, and infrared light is emitted from an emitting end of the infrared detecting device to a receiving end, and an infrared light parallel to the bottom wall 10 of the body is formed in the initial arm 12 and the alternative arm 13 where the detecting assembly 3 is located. When the mouse passes through the detection area between the emitting end and the receiving end, as shown in fig. 6, the infrared light is shielded by the body of the mouse, and the receiving end cannot receive the light emitted by the emitting end, so as to determine that the mouse has entered the detection area, and at this time, the detection assembly 3 sends a signal (e.g., a low level signal) to the control unit to confirm the action state of the mouse.

With continued reference to fig. 1-4 and 7, in one embodiment of the exercise device, the body bottom wall 10 has an outer extension section disposed outside the outer peripheral sides of the starting arm 12 and the alternative arm 13, and the outer extension section has a mounting hole 100 formed therein. The supply assembly 4 includes a water supply unit 41, a pump body 42 and a water inlet pipe 43 connected in sequence. The water source unit 41 is used for supplying water, and the pump body 42 provides a pressure to drive the water to flow out from the water source unit 41. Holes are formed in the body side wall 11 at the top of the starting arm 12 and the alternative arm 13, and the water inlet pipe 43 penetrates into the starting space 120 and the alternative space 130 in the training device from the holes formed in the body side wall 11 at the top of the starting arm 12 and the alternative arm 13 corresponding to the height of the mouse. Driven by the pump body 42, a water flow is directed from the water supply unit 1 via the water inlet pipe 43 into the training device. In one embodiment, the water supply unit 41 is a cup-shaped container containing water that is secured in the exercise device by mounting holes 100. In one embodiment, the pump body 4 is a peristaltic pump, so that the discharge conditions and the discharge volume into the training device can be controlled. In one embodiment, the water inlet pipe 43 is disposed at a distance of 4 cm above the bottom wall 10 of the body at the top of the starting arm 12 and the alternative arm 13. In one embodiment, the water inlet pipe 43 is provided with a metal water nozzle at the end after entering the training device.

Fig. 8 shows a schematic cross-sectional view of an embodiment of the second driving unit 6, and the second driving device 6 is a steering engine, and includes a driving motor 61, a position sensor (not shown in the figure), and a swing arm 62, wherein the swing arm 62 is connected to the bottom of the door body 2, the driving motor 61 drives the swing arm 62 to rotate, so as to drive the door body 2 to rotate, and the position sensor detects a moving angle of the swing arm, so as to complete switching between an open state and a closed state. The second driving means 6 may be connected to the body bottom wall 10 by fasteners as shown, or may be connected by other suitable means. Similarly, the first driving device 5 may also be a steering engine, and the swing arm thereof is connected to the turntable 14, so as to drive the turntable 14 to rotate when in the working state.

In one embodiment of the training device, the starting arm 12 has a length and width that is greater than the length and width of the alternate arm 13, and the starting arm 12 and the alternate arm 13 have a length and width that are configured to allow the mouse to move freely therein. In some other embodiments, the creatures trained in the training device are animals other than mice, in which case the size and height of the training device, including the height of the detection assembly 3 and the feeding assembly 4, will vary depending on the animal selected.

In one embodiment, the exercise device is made of acrylic, which has good chemical stability and weather resistance.

The training method adopting the space working memory behavior training device comprises the following steps:

as shown in fig. 9, the training method includes three stages of adaptation, pre-training and formal training, water is used as reward in the training, in order to keep the power of the mouse, the mouse needs to be restricted from getting food in the training process to keep the demand of the mouse for food, in the embodiment, the food is water, in the training process, the mouse needs to be restricted from getting drinking water to keep thirst, and meanwhile, the weight of the mouse needs to be monitored daily to ensure that the weight is not less than 80% of the initial weight. The mice are cut off 0-24 hours before training, and in another embodiment, the mice are gradually restricted from drinking water one week earlier; the drinking water is supplemented properly according to the weight change condition and the state (hair color, body type, athletic ability and the like) of the mouse, and in the training method, the mouse can obtain enough water in a task during pre-training and formal training without additional supplement.

The adaptation phase allows the mice to move freely in the starting arm 12 and the alternative arm 13 each day, while the detection assembly 3, the feeding assembly 4, the first drive unit 5 and the second drive unit 6 in the training device may all be switched off, in one embodiment the adaptation phase is for a period of 2 days, allowing the mice to explore freely for 30-60 minutes each day. After the daily adaptation, the mice were returned to their cages, each mouse supplemented with 1-2 ml of water, and the weight of the mice was weighed. The adaptation phase aims to adapt the mouse to the training device and the experimenter, and avoids the stress state of the mouse as much as possible.

The pre-training phase is intended to let the mouse learn to get water by the "alternative arm 12-starting arm 13" turn back and adapt to the noise of the door 2 opening and closing, the first drive unit 5 and the second drive unit 6 running. In one embodiment, the pre-training period is 2-5 days. The pre-training phase includes a sample period, a delay period, and a selection period. Fig. 10A to 10C show schematic diagrams of mice in the sample phase, delay phase and selection phase in pre-training, respectively.

In the sample period, the control unit controls the door body 2 of the starting arm 12 and any one of the candidate arms 13 to enter an open state to allow the mouse to pass through, the candidate arm 13 entering the open state is defined as a matching arm 13a, the other candidate arms 13 are defined as unmatched arms 13b, the candidate space 130 of the matching arm 13a is defined as a matching space 130a, and the candidate space 130 of the unmatched arm 13b is defined as a unmatched space 130 b. Specifically, as shown in fig. 10A, the gate 2 in the leftmost candidate arm is randomly selected to be opened in the sample period, and at this time, the leftmost candidate arm becomes the matching arm 13a, and the remaining three candidate arms become the non-matching arms 13 b. When the detecting member 3 in the matching arm 13a detects the entry of the mouse, the supply member of the matching arm 13a supplies 2 to 4 microliters of water to the matching space 130a, and preferably, the supply member supplies 3.5 microliters of water to the matching space 130 a.

As shown in fig. 10B, after the sample period ends, the mouse returns to the start arm 12, and then enters the delay period, and when the detection assembly 3 of the start arm 12 detects that the mouse enters, the control unit controls all the door bodies 2 to enter the closed state. The feed assembly 4 then feeds 2-4 microlitres of water into the initial space. Preferably, the supply assembly 4 supplies 3.5 microliters of water to the initial space 120. After completion, the gate bodies 2 of the matching arm 13a and any one of the non-matching arms 13b are brought into an open state, and the mouse is confined in the origin arm 12 for a while.

As shown in fig. 10C, after the mouse waits for a period of time, the selection period is entered, in the selection period, the control unit controls the door 2 of the start arm 12 to enter the open state, the mouse is allowed to leave the start space 120 and enter the matching space 130a or the unmatched space 130b, when the detection assembly 4 disposed in the matching arm 13a or the unmatched arm 13b detects the entry of the mouse, no matter how the mouse is selected, the feeding assembly in the matching arm 13a or the unmatched arm 13b into which the mouse enters supplies 4-6 microliters, preferably 5.5 microliters of water into the training device, and the door 2 of the matching arm 13a or the unmatched arm 13b into which the mouse does not enter enters the closed state.

After the selection period, the mouse will return to the initial arm 12, and then enter the trial period, when the detection component 3 of the initial arm 12 detects the mouse entering, the control unit controls the door 2 to enter the closed state, the feeding component 3 feeds 2-4 microlitres, preferably 3.5 microlitres of water into the initial space 120, the mouse is limited to the initial space 120, and when one trial period is completed, the mouse waits for the next trial period in the initial space 120.

The cycle of "sample period-delay period-selection period-trial interval" is repeated until the number of trial times reaches the preset value n. In one embodiment, n is 48 times, and it should be noted that a large amount of exploratory behavior of the mice can still be observed in the early stage of pre-training, and all the trials cannot be completed within 3 hours; with the increase of training days, the mice are gradually familiar with the adaptive training device and rules, all trials can be completed within 2 hours, and the next stage of formal training can be carried out.

The formal training days are 3-7 days and can be adjusted according to requirements. The formal training trial structure is similar to the pre-training, and comprises a sample period, a delay period and a selection period. Unlike pre-training, where the "no match" rule is followed in formal training, the mouse needs to remember the location of the matching arm 13a during the delay period and to correctly select the non-matching arm 13b during the selection period in order to receive the water reward. Specifically, a detailed flowchart is shown by fig. 11.

Fig. 12A to 12C show schematic diagrams of mice in the sample phase, delay phase and selection phase, respectively, in the formal training.

In the formal training sample period, similar to the pre-training sample period, the control unit controls the gate body 2 of the starting arm 12 and any one of the candidate arms 13 to enter the open state to allow the mouse to pass through, the candidate arm 13 entering the open state is defined as a matching arm 13a, the other candidate arms 13 are defined as unmatched arms 13b, the candidate space 130 of the matching arm 13a is defined as a matching space 130a, and the candidate space 130 of the unmatched arm 13b is defined as a unmatched space 130 b. Specifically, as shown in fig. 12A, the gate 2 in the leftmost candidate arm is randomly selected to be opened in the sample period, and at this time, the leftmost candidate arm becomes the matching arm 13a, and the remaining three candidate arms become the non-matching arms 13 b. When the detecting member 3 in the matching arm 13a detects the entry of the mouse, the supply member of the matching arm 13a supplies 2 to 4 microliters of water to the matching space 130a, and preferably, the supply member supplies 3.5 microliters of water to the matching space 130 a.

As shown in fig. 12B, after the formal training sample period is over, the mouse returns to the starting arm 12, and then enters into the formal training delay period, and when the detecting assembly 3 of the starting arm 12 detects that the mouse enters, the control unit controls all the door bodies 2 to enter into the closed state. The feed assembly 4 then feeds 2-4 microlitres of water into the initial space. Preferably, the supply assembly 4 supplies 3.5 microliters of water to the initial space 120. After completion, the gate bodies 2 of the matching arm 13a and all the non-matching arms 13b are brought into an open state, and the mouse is confined in the origin arm 12 for a while.

As shown in fig. 10C, after the mouse waits for a period of time, the mouse enters a formal training selection period, in the selection period, the control unit controls the door body 2 of the starting arm 12 to enter an open state, the mouse is allowed to leave the starting space 120 and enter the matching space 130a or the unmatched space 130b, when the detection component of the matching arm 13a detects that the mouse enters the detection component 3, the detection component 3 returns an "error" signal to the control unit, the control unit controls the feeding component 4 not to supply water to the training device until the mouse returns to the starting space 120, and the selection period is ended; when the detecting component 3 of the unmatched arm 13b detects the mouse entering, the detecting component 3 returns a 'correct' signal to the control unit, the control unit controls the feeding component 4 to feed 4-6 microliters, preferably 5.5 microliters of water into the unmatched space 130b, and the door body 2 of the matched arm 13a enters a closed state. In one embodiment, to maximize the difference between the "correct" and "incorrect" water volume, the initial arm 12 does not deliver water for the delay period, and only delivers 3.5 microliters of water during the test interval when the previous test was correct.

The cycle of "sample period-delay period-selection period-trial interval" is repeated until the number of trial times reaches the preset value n. In one embodiment, n is 48 times,

the results of the performance using the training apparatus and training method are shown in fig. 13. In training, the delay period time length is 5 seconds, and the trial interval time length is 10 seconds. The figure shows the average accuracy of 11 mice in formal training, which is calculated by the following formula:

the accuracy is the number of correct trials ÷ total number of trials × 100%

As can be seen in fig. 13, the mice exhibited a preference for the non-matching arms during the pre-training period and the correct rate was much higher than the random level (50%) on the first day of formal training. This behavior appeared very stable, and mice did not improve significantly in accuracy with increasing training days, but remained at a higher level (around 80%).

Fig. 14 shows the accuracy of 6 mice under conditions of 5, 30 or 60 seconds of delay period to show that the accuracy of mouse behavior is affected by the length of the delay period. Wherein, under the condition of short delay period (5 seconds), the accuracy of the mouse is high (about 90 percent); when the delay period is prolonged to 30 seconds, the accuracy of the mice is reduced to about 80 percent; when the delay period is further extended to 60 seconds, the mouse accuracy is reduced to about 70%. This behavior well simulates the "decline over time" behavior of working memory, proving that this behavioral paradigm is indeed a working memory task.

In one embodiment of the training method, in the delay period of the pre-training stage and the delay period of the formal training stage, after the door 2 enters the closed state, the control unit controls the turntable 14 to rotate by any angle, wherein the angle is a random angle, so as to prevent the mouse from leaving odor on the sample arm as a prompt.

In one embodiment of the training method, the length of the mouse waiting time in the delay period of the pre-training phase and the delay period of the formal training phase is 5 to 90 seconds.

In one embodiment of the training method, the length of time for the mouse to wait for the next trial training is greater than 10 seconds in the trial interval of the pre-training phase and the trial interval of the full training phase.

In one embodiment of the training method, the length of time for the mouse to wait for the next trial training in the trial interval of the pre-training phase and the trial interval of the full training phase is 2 times the length of time for the mouse to wait in the delay period of the pre-training phase and the delay period of the full training phase.

In one embodiment of the training method, the number of trials n in the pre-training phase and the formal training phase is between 10 and 80, and in some embodiments, between 40 and 60.

Although the present invention has been disclosed in terms of the preferred embodiment, it is not intended to limit the invention, and variations and modifications may be made by one skilled in the art without departing from the spirit and scope of the invention. Therefore, any modification, equivalent change and modification of the above embodiments according to the technical essence of the present invention are within the protection scope defined by the claims of the present invention, unless the technical essence of the present invention departs from the content of the present invention.

Claims

1. A spatial working memory behavior training device, comprising:

2. The spatial working memory behavior training device of claim 1, wherein the detection component is disposed on the body sidewall in the initial arm and the alternate arm corresponding to the height of the mouse.

3. The spatial working memory behavior training device according to claim 2, wherein the detection assembly comprises a transmitting unit and a receiving unit, the transmitting unit and the receiving unit are respectively arranged on the side wall of the body on both sides of the initial arm and both sides of the alternative arm;

4. The spatial working memory behavior training device of claim 1, wherein the feeding assembly is a water supply assembly comprising a water source unit, a pump body and a water inlet pipe penetrating into the training device from the body side wall of the initial arm top and the alternative arm top corresponding to the height of the mouse.

5. The spatial working memory behavior training device as claimed in claim 4, wherein the body base plate has an outer extended section disposed outside the outer circumferential sides of the starting arm and the alternative arm, and the outer extended section is opened with a mounting hole for receiving the water supply unit.

6. The space working memory behavior training device as claimed in claim 1, wherein the first driving unit and the second driving unit are steering engines, and swing arms of the steering engines are respectively connected with the door body and the turntable.

7. A method for spatial working memory behavior training, characterized in that it employs the spatial working memory behavior training device of any one of claims 1-6,

for the pre-training or formal training:

8. The method for spatial working memory behavior training as defined in claim 7, wherein during the delay period, the turntable is rotated by an arbitrary angle after the starting arm is closed.

9. The method for spatial working memory behavior training as in claim 7, wherein prior to pre-training, the method further comprises an adaptation period, opening the initial arm and all alternate arms, allowing the mouse to explore freely in the training device.

10. The method for spatial working memory behavior training as described in claim 7, further comprising the step of stopping or limiting the access of the mouse to food prior to the acclimation period to maintain the mouse's need for food.

11. The method for spatial working memory behavior training as defined in claim 7, wherein the latency of the delay period is 5 to 90 seconds.

12. The method for spatial working memory behavior training as claimed in claim 7, wherein the trial number n is between 10 and 80 or between 40 and 60.

13. The method for spatial working memory behavior training as defined in claim 7, wherein the trial pause has a latency length greater than 10 seconds or 2 times the latency length of the delay period.