CN114847224A - Device and method for detecting sound frequency resolution capability of mouse - Google Patents
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Abstract
The invention discloses a system for detecting the sound frequency resolution capability of a mouse, which comprises: the system comprises an upper computer, an I/O processor and a mouse experimental box; the upper computer is used for monitoring the experimental device, controlling the state of the I/O processor and storing experimental data; the I/O processor is used for being connected with devices arranged inside and outside the mouse experimental box and processing data obtained by the devices. The mouse experiment box is a sound insulation box, and the sound insulation box internally comprises a camera, an LED lamp bead, a loudspeaker, a mouse retainer, a head retainer, a water nozzle made of a stainless steel capillary tube and a superfine optical fiber or infrared electronic geminate transistor connected with the water nozzle; and a relay, an electromagnetic valve, an optical fiber amplifier, a medical infusion bottle and an infusion tube are arranged outside the sound insulation box. The invention also discloses a method for detecting the sound frequency resolution capability of the mouse by using the system.
Description
Technical Field
The invention belongs to the technical field of life science and medicine, and relates to a device and a method for detecting the sound frequency resolution capability of a mouse.
Background
In the 21 st century that mankind has achieved a sea visit in flying, mankind has not yet understood how to create curiosity with the brain itself. Humans are a member of many mammals in nature, and different mammals share similar neural structures. Therefore, the research on the behavior of small model animals and the neural circuits and molecular basis of the brain is of great significance for understanding the structure and function of the human brain. Human beings, the most clever mammals in nature, have evolved high-level brain structures over the years that give us the ability to communicate with other individuals using language. However, since small model animals do not have language function, a certain experimental device and strategy are needed to find out their subjective behaviors.
Sensory information (e.g., sound, light) in the environment inputs sensory stimuli to the higher nerve center through the sensory organs and forms sensations in the sensory related areas of the brain. The function of a neural network composed of brain sensory neurons can directly influence the formation of sensations. Taking auditory function as an example, sound information is converted into nerve impulses by the cochlea, and finally forms auditory sense in the primary auditory cortex through processing and transmission of a series of auditory nuclei (such as cochlear nucleus and thalamus). Research shows that the network function of the primary auditory cortex plays an important role in auditory function. Therefore, exploring sensory behaviors of small model animals is essential for functional studies of the brain.
Auditory, i.e., the brain's ability to perceive sounds in the environment. The human hearing ability is often used to parse language semantics. The elements of the sound are split into frequency, repetition rate and sound direction. These three acoustic elements can store a large amount of linguistic information. The human brain's perceptibility of these three elements of sound directly affects the understanding of speech.
It is generally believed that physiological changes in the auditory nucleus in the central system can affect the auditory function of an individual. Therefore, in order to understand the auditory function of an individual, physiological research means such as auditory induction of brainstem response can reflect the transmission process of auditory information from the level of brain electricity and extracellular recording can reflect the function of neurons from the level of cells are often used. These measures can reflect the physiological changes of the central auditory nucleus and indirectly reflect the auditory function of the individual.
In view of the fact that the mice cannot complain about subjective feelings, special experimental devices and strategies are needed to reflect the auditory function of the mice from the behavior level. Currently, methods to ascertain mouse auditory function typically rely on either classical conditioned reflex (baroproff conditioned reflex behavior) or operative conditioned reflex (smid conditioned behavior). Classical conditioned response refers to the multiple association of one stimulus with another unconditional stimulus with a reward or penalty that allows an individual to learn to elicit a conditioned response similar to an unconditional response when the stimulus is presented alone. Operative conditioned reflex divides the responsiveness and operability of the unconditional stimulus response in classical conditioned reflex, and is typically used to maintain classical conditioned reflex.
Disclosure of Invention
In order to solve the defects of the prior art, the invention aims to provide a device and a method for detecting the sound frequency resolution capability of a mouse. The basic principle of the strategy of the invention is to indirectly find the sensibility of the mouse to the paired acoustic information by utilizing the response of the mouse to the reward desire under the classical conditioned reflex and the operational conditioned reflex. At present, this type of behavior paradigm is often referred to as Go/No Go behavior.
The invention aims to invent a device and a method for exploring the sound frequency susceptibility of a mouse by means of a classical Go/No Go behavior paradigm. Since the small model animal cannot complain about the subjective feeling, the sound frequency distinguishing function of the small model animal can be known through the device and the strategy. The present invention detects only the frequency-resolved function of small model animals at the animal behavioral level.
The invention provides a system for detecting the sound frequency resolution capability of a mouse, which comprises: the system comprises an upper computer, an I/O processor and a mouse experimental box;
the upper computer can generally use a computer and is used for monitoring the experimental device, controlling the state of the I/O processor and storing experimental data;
the I/O processor is used for being connected with devices arranged inside and outside the mouse experiment box and processing data obtained by each sensor.
The mouse experiment box is a sound insulation box, and the sound insulation box internally comprises a camera, an LED lamp bead, a loudspeaker, a mouse retainer, a head retainer, a water nozzle made of a stainless steel capillary tube and a superfine optical fiber or infrared electronic geminate transistor connected with the water nozzle;
and a relay, an electromagnetic valve, an optical fiber amplifier, a medical infusion bottle and an infusion tube are arranged outside the sound insulation box.
The I/O processor is connected with the LED lamp beads in the sound insulation box to form an error prompt circuit which is used for prompting error events and missed events of the mouse in a training task;
the I/O processor is connected with the electromagnetic valve through a relay, and forms a drinking water reward circuit together with the medical transfusion bottle and the transfusion tube, and the drinking water reward circuit is used for rewarding drinking water for the mouse through the water nozzle when an avoiding and correct hitting event occurs in a training task;
the I/O processor is connected with a water nozzle in the sound insulation box through a superfine optical fiber and an optical fiber amplifier or an infrared electronic geminate transistor to jointly form a water licking sensing circuit which is used for sensing the water licking behavior of a mouse in a training task;
the I/O processor is connected with the loudspeaker to form an auditory stimulation circuit which is used for giving sound stimulation in a training task.
The electromagnetic valve is arranged outside the sound insulation box, a 5V high-level signal output by the I/O processor is output to a relay signal end, a relay control end is connected to the electromagnetic valve, and the electromagnetic valve controls a water path formed by the medical infusion bottle and the infusion tube; the electromagnetic valve is in a normally closed state when not electrified, and after the relay is electrified, the electromagnetic valve is started, the water way is communicated, and the mouse is drunk.
The four types of circuit switches are controlled by the I/O processor, the I/O processor is controlled by a program of the upper computer, and the upper computer controls the whole training process by detecting the state of the I/O processor and acquires and stores experimental data.
The head fixer is used for fixing the head of a mouse;
the mouse retainer is used for retaining a mouse, so that the limb behaviors of the mouse are limited;
the superfine optical fiber is used for sensing the water licking behavior of a mouse, the optical fiber is communicated with a light path, and the blocking state of the light path can be converted into an electric signal by the optical fiber amplifier and transmitted to the I/O processor;
the optical fiber amplifier is used for processing the photosensitive signal, and light emitted by the optical fiber is converted into a continuous level signal by the optical fiber amplifier after being blocked by the mouse tongue and is transmitted back to the I/O processor;
the infrared electronic pair tube replaces an ultrafine optical fiber and an optical fiber amplifier to work independently, and senses the water licking behavior of the mouse through whether the emitted infrared light beam is blocked or not;
the water nozzle is used for supplying water to the mice in the experiment process;
the medical infusion bottle and the infusion tube are used for a drinking water waterway and are controlled by an electromagnetic valve;
the camera is used for detecting the state of the mouse;
the system also includes wires for connecting the various components of the system.
The logic principle of the hardware design of the system is as follows: the auditory stimulation circuit, the licking sensing circuit, the drinking reward circuit and the error prompt circuit transmit the circuit detection results to the I/O processor hardware, the detection results of all the circuits are processed through a pre-designed I/O processor program, and the upper computer monitors the program and stores the detection data of all the circuits.
In the water licking sensing circuit, if the I/O processor is connected with the water nozzle through the superfine optical fiber and the optical fiber amplifier, the brightness of light blocked in the process of licking water by the mouse tongue is converted into an analog electric signal through the optical fiber amplifier, namely the more the tongue is close to the superfine optical fiber, the larger the change of the generated analog electric signal is; the detection of the water licking behavior of the mouse is realized; if the I/O processor is connected with the water nozzle through the infrared electronic geminate transistors, the mouse tongue licks water to block infrared beams emitted by the infrared electronic geminate transistors, and the water licking process of the mouse is sensed and detected.
The invention also provides a method for detecting the sound frequency resolution capability of a mouse by utilizing the system for non-disease diagnosis or treatment, which comprises the following steps:
step one, processing an experimental mouse, and installing a fixer;
step two, performing pre-training, single-sound training and double-sound training on the treated experimental mouse in sequence to enable the auditory sense resolving power of the experimental mouse to reach a set threshold value;
and step three, carrying out resolution capability detection on the experimental mouse by using the designed detection sound.
In the first step, the fixator is adhered to the skull of the mouse exposed after the scalp is cut off through tissue glue or 502 glue, and the wound is sutured; the fixator is used for fixing the head of a mouse.
And in the second step, the pre-training is specifically to place a water nozzle connected with a superfine optical fiber and an optical fiber amplifier or an infrared electronic geminate transistor near the mouth of the mouse, guide the mouse to lick water, and enter the next stage of training after the mouse can successfully lick the water for 100 times.
In the second step, the monophonic training is specifically to stimulate the mouse by using the target sound, guide the mouse to carry out water licking behavior in a preset time window after the target sound is stimulated, and enter the next stage of training when the proportion of the times of the water licking behavior in the total times after the target sound is stimulated reaches 70%; the time of the time window is gradually reduced according to 3s,2s and 1.2s, so that the mouse is forced to make water licking reaction as soon as possible, and the overlong water licking time window can increase the working memory component in training.
In the second step, the binaural training is specifically to set a target sound and a non-target sound with two different sound frequencies, where the target sound is 0.75-fold pitch distance from the non-target sound, for example: non-target sound of 10000Hz (target sound) × 2 -0.75 Carrying out multiple rounds of training at 5946Hz, after one round of training is finished, increasing the proportion of non-target sounds (realized by the proportion of the non-target sounds in the program random number selection), and recording data of behavior of each mouse in the double-sound training; the behavior of the mouse in the double-sound training comprises the following steps: licking after target acoustic stimulation is recorded as "hit", and licking after non-target acoustic stimulation is recorded as "missError, no licking of water under non-target acoustic stimulation is recorded as "avoidance", and no licking of water after target acoustic stimulation is recorded as "missed"; calculating an expression score P from the four numbers of behavioral expressions in a fixed number of stimuli, P ═ H-H × F; wherein, H is the number of hits/number of target acoustic stimuli, and F is the number of errors/number of non-target acoustic stimuli; when the proportion of the last round of non-target sounds in the two-sound training reaches 70% and the performance score exceeds 70%, the mouse training is finished.
In the double-sound training, the proportion of the target sound is not high, the animal can make a blind selection decision by the high proportion of the target sound, namely, the animal can lick water only without distinguishing signals, so that the animal can drink water too early, the training cannot be carried out, and the target sound with low probability is used for inhibiting the desire of the animal to drink water and improving the expectation of the animal to the next training. The decision to have a high performance score is the hit to avoidance event ratio, independent of the non-target acoustic ratio.
In the third step, the sound frequency resolution capability of the mouse is detected through test sounds with different structure sound frequencies, and the performance score P '═ H' -H '× F' of the mouse under the stimulation of each sound frequency is obtained; where H 'is the number of hits/target number of acoustic stimulations, and F' is the number of frequency errors/non-target number of acoustic stimulations.
The test sound designed in the method is pure tone with single frequency, and the test sound can be changed into repeated pure tone or repeated noise. A repeated tone refers to a sound composed of a plurality of pure tones or noises, and is characterized by the speed of sound presentation, having a time-phase characteristic. Based on the training logic of the invention, the repeated sounds with different repetition rates are used as the target sound or the non-target sound, and the method can be used for detecting the distinguishing capability of the mouse on the sound repetition rate.
The method for detecting the sound frequency resolution capability of the mouse in the invention is not used for the purpose of disease diagnosis or treatment.
The beneficial effects of the invention include: the invention has the advantages that the invention is noninvasive, the frequency resolution capability of the animal can be known at the behavior level, and the animal cannot be hurt. Second, the present invention reflects the frequency resolution capability of mice. Most behavioral auditory function tests only understand the change of auditory threshold and cannot reflect the sound discrimination ability of mice. Third, the present invention has general probabilitism in many nervous system problems. The invention can provide a new research method for auditory function research from a behavior level.
Drawings
FIG. 1 is a schematic view of an experimental apparatus according to the present invention. (A, hardware equipment installation schematic diagram; B, hardware design logic schematic diagram.)
Fig. 2 is a Matlab program control panel. From left to right, respectively are a pre-training stage control program interface, a dual-sound resolution stage control program interface and a resolution detection stage control program interface.
Figure 3 is a graph of behavioral events of mice during training.
FIG. 4 shows the selection rate of the target sounds and the non-target sounds of the mouse before and after the binaural cue discrimination task training according to the embodiment of the present invention.
FIG. 5 is a graph showing the performance score curves of mice according to the present invention. (A, performance score curve per mouse; B, average performance score curve.)
FIG. 6 is an auditory frequency-resolved characterization of an autism model animal in an embodiment of the invention. A, frequency resolved performance score curves for both groups of mice. B, mean frequency performance score curves for both groups of mice. C, two groups of mice auditory resolution threshold (frequency difference at 50% performance score).
Detailed Description
The present invention will be described in further detail with reference to the following specific examples and the accompanying drawings. The procedures, conditions, experimental methods and the like for carrying out the present invention are general knowledge and common general knowledge in the art except for the contents specifically mentioned below, and the present invention is not particularly limited.
The invention comprises a hardware device for realizing automatic control and an experimental method for detecting the resolution capability of animals on sound frequency. Based on the classical go/no go experimental paradigm, the invention uses sounds of different frequencies as conditional and unconditional stimuli, and calculates the performance score of the mouse at the corresponding frequency by counting four events (hit, avoidance, error and miss, respectively) of the mouse under the paradigm. Thereby judging the discrimination ability of the mouse to the frequency sound. The training automation is realized by a DAQ digital acquisition card and Matlab programming of a national instrument.
1. The invention provides a detection device
The hardware device of the invention consists of a mouse head fixer, a mouse retainer, a loudspeaker, an optical fiber amplifier, superfine optical fibers, LED lamp beads, an I/O processor (National Instrument, NI-USB 6001), a relay, an electromagnetic valve (Kammer), a water nozzle made of stainless steel capillary tubes, a medical transfusion bottle and a transfusion tube, a lead, a camera and a computer. In order to ensure that the experimental environment is not interfered by the external environment, the experimental device is assembled in a sound insulation box with a ventilation function (figure 1A). The LED lamp bead, the electromagnetic valve, the sensor (superfine optical fiber and optical fiber amplifier can be selected, or infrared electronic geminate transistors are adopted, and superfine optical fiber and optical fiber amplifier are mainly used in the invention) and the loudspeaker are connected with the I/O processor to respectively form an error prompt circuit, a drinking water reward circuit, a water licking sensing circuit and an auditory stimulation circuit. The I/O processor is controlled by an upper computer (computer). The upper computer can monitor the whole experimental process through the processor state control and the camera (fig. 1B). When the loudspeaker plays a target sound (Go sound), the mouse touches the sensor in the time window to give a reward for drinking water (the electromagnetic valve is opened); when a loudspeaker plays a target sound (Go sound), a mouse does not touch a sensor in a time window, gives a light alarm and delays for 6s to enter the next stimulation cycle (LED lamp is turned on); when a horn plays a non-target sound (No Go sound), a mouse touches a sensor in a time window, gives a light alarm and delays for 6s to enter the next stimulation cycle (the LED lamp is turned on); when the horn plays a non-target sound (No Go sound), the mouse does not touch the sensor within the time window, and does not directly enter the next stimulation cycle for the reward.
2. Software for use with the invention
The control software is realized by Matlab 2019(mathwork) programming. The software is divided into a pre-training program, a dual-sound distinguishing program and a detection program according to a training process. The software panel is shown in fig. 2. The pre-training program is used for animals to establish licking water reflexes, and the manual water supply function can also be used for water pipe air discharge. The dual sound discrimination program can automatically run the animal's discrimination program for both sounds. The panel may set the frequencies of the target sound and the non-target sound. The ratio of the occurrence of the two sound frequencies is adjusted. The animal's response time window was adjusted. The detection program can automatically run a detection program for distinguishing 6 sounds (1 target sound and 5 non-target sounds) by the animal, and the panel can adjust the sound frequency of the 6 sounds and adjust the reaction time window of the animal.
3. Experimental methods of the invention
The test object of the invention is a rodent mouse, comprising a plurality of experimental animal strains, such as: BALB/C, C57BL/6 and various transgenic mice, or rodents of similar body type weighing less than 50 g. After the mice were anesthetized by intraperitoneal injection of pentobarbital anesthetic or isoflurane gas anesthesia, the scalp of the mice was cut off and the parietal bones were exposed. The fixture was glued to the mouse skull using tissue glue or 502 glue. The wound is closed with needles and threads or glued with tissue glue to prevent infection. The mice after the operation are placed in a thermostat and are returned to the mouse cage for feeding after being clear-headed. If the wound is infected, the wound can be smeared with erythromycin ointment or corresponding topical antibiotics.
The logic for rewarding drinking to distinguish sounds was learned by the mice. The present invention requires gradual training of mice. The training process is divided into 5 stages.
1) A pre-training stage: in order to adapt the mice to the experimental device, anxiety was reduced and the conditioned reflex of water intake achieved by licking the water gap was grasped. Mice need to be pre-trained prior to formal training. The experimenter needs to hold the mouse on the hand for pacifying, and squeeze out a small water drop by using a syringe to guide the mouse to lick water. Then the sensor is fixed in an animal retainer, and the distance between the sensor and the mouse mouth is adjusted, so that the sensor can correctly sense the distance of the mouse licking water. The pre-training program was turned on and water was manually supplied. After the mouse licks water, automatic water supply is changed. When the mouse can successfully lick water 100 times, the next stage of learning can be entered.
2) A single sound training stage: this stage required the mice to learn to lick water within a 1.2s time window after the target acoustic stimulation. The laboratory technician immobilizes the mouse in front of the laboratory bench to pacify it. The mice were fixed in an animal holder and the binaural resolution program was turned on with the target sound set at 10000Hz at a ratio of 100%. The reaction time window can be gradually adjusted to 1.2s from 3s (three processes of 3s-2.1s-1.2s can be divided), the stimulation is performed for 300 times every day, water licking within the window time after the mouse target sound stimulation is recorded as event hitting (Hit), and a water drop (6-7ul) reward is obtained. After the target sounds, the animal does not lick water and is recorded as a misevent (miss), no water is given, and the next training is delayed for 6s after the light is turned on for warning. The present invention divides 50 training sessions into 1 session, and counts the accuracy in the session (the accuracy is the number of hits/50). The mouse accuracy reaches 70% after 2 rounds are continued, and then the next stage of learning can be carried out.
3) A binaural training phase I: in this stage, the mouse needs to learn to distinguish two sounds, namely the target sound and the non-target sound. The experimenter secured the mouse in front of the laboratory bench to pacify it. The mice were fixed in an animal holder and the binaural resolution procedure was opened with the target acoustic frequency set to 10000HZ, the non-target acoustic frequency set to 5946HZ and the reaction time window 1.2 s. The program runs 300 times of training, the first 100 times of training set the ratio of target sound to non-target sound stimulation to be 7:3, the second 100 times of training set the ratio of target sound to non-target sound stimulation to be 5:5, and the last 100 times of training set the ratio of target sound to non-target sound stimulation to be 3: 7. As shown in fig. 3, the mice had a total of four event manifestations in the dual-sound resolution task, namely hit (licking water after target acoustic stimulation), error (licking water after non-target acoustic stimulation), avoidance (licking water without non-target acoustic stimulation), and miss (licking water after target acoustic stimulation). The number of occurrences of these four events in each session (50 stimulations) is counted, and an expression score for the session can be calculated (P ═ H-hxf, H ═ number of hits/number of target acoustic stimulations, and F ═ number of errors/number of non-target acoustic stimulations). The aim of the stage is to adapt the stimulation ratio of the target sound to the non-target sound in the double-sound training, so that the learning of the next stage can be directly carried out by only carrying out the training for 1 day.
4) A binaural training phase II: the training program in this phase is the same as in the previous phase, reducing the proportion of target vocal stimulation, which is 30% (making it more difficult for the mice to obtain rewards). The experimenter secured the mouse in front of the laboratory bench to pacify it. The mice were fixed in an animal holder and the binaural resolution program was opened with the target acoustic frequency set at 10000Hz, the non-target acoustic frequency set at 5946Hz and the reaction time window 1.2 s. Performance scores were calculated for each mouse. The mouse performance score of more than 70% in 2 consecutive rounds is up to standard. The detection phase can be entered.
5) A resolution detection stage: in the stage, 4 interference sounds are added between target sound (10000Hz) and non-target sound (5946Hz), wherein the interference sounds are 9012 Hz, 8122 Hz, 7320 Hz and 6597Hz respectively. The relationship between every two sounds is 0.15 octave. The smaller the difference between the non-target sound frequency and the target sound frequency is, the more difficult it is for the mouse to distinguish the target sound from the non-target sound. And calculating the performance score of the mouse under each sound stimulation, namely, the distinguishing capability of the mouse on the sound frequency can be ascertained. After the mice were fixed in the animal immobilizer, the frequency-resolved detection procedure was turned on. The performance score of each part under each frequency stimulation is counted (P ═ H-hxf, H ═ hit frequency/target number of times of acoustic stimulation, and F ═ frequency error frequency/number of times of non-target acoustic stimulation). To eliminate the effect of non-experimental factors on the results, the present invention chooses to eliminate the first two and the last two (for the convenience of statistical data, the present invention divides 50 tests into 1 test, and 1 test includes 1 randomly occurring sound stimulus which may contain one of different frequencies, and the data of the mouse's response to this sound stimulus (fig. 3), to obtain the average performance score curve of the mouse.
The experimental results are as follows:
1. success rate before and after double-sound training of mice.
The present invention tested 8C 57/BL6 wild-type mice using a frequency-resolved detection task. As shown in fig. 4, the selection of the target sounds was significantly higher than the non-target sounds after the mice underwent the binaural resolution task. Also, as training progresses, the mice have a lower selectivity for non-target sounds. Thus, the ability of the mice to accurately grasp the ability to distinguish the diphone and obtain a reward for drinking water was demonstrated.
2, mouse performance score curves.
Under the frequency-resolved detection task, the performance scores of 8 mice are shown in fig. 5. According to the invention, the performance score of the mouse is counted according to the interval difference between the target sound and the non-target sound. The results show that the higher the resolving power of the mouse, the easier it is to resolve as the difference between the target and non-target sound frequencies increases. This allows the mouse to be plotted for performance score (FIG. 5A). The average performance score curves were obtained by averaging the performance score curves of the mice of the same group (FIG. 5B)
3, the compound is used for characterizing the reduction of the auditory function of the autism model animal.
The present invention tested autism model mice using the frequency-resolved detection task (fig. 6A). The results of comparison with control mice show that the frequency resolution performance score curve of the mice of the autism model is significantly lower than that of the control mice (FIG. 6B, one-way ANOVAwith post hoc student Newman-Keuls test; frequency difference is 0.3, P < 0.05; frequency difference is 0.6, P < 0.05). The 50% performance score was chosen as the criterion and the frequency difference at this performance score was used as the mouse auditory resolution threshold, and statistical analysis of the two groups of mice revealed that the frequency resolution threshold was higher for the model group than for the control group (FIG. 6C, student t-test, P < 0.05). The results can reflect that the auditory frequency resolution of autism model mice is significantly lower than that of control mice. In fig. 6, the model group represents autism model mice.
The protection of the present invention is not limited to the above embodiments. Variations and advantages that may occur to those skilled in the art may be incorporated into the invention without departing from the spirit and scope of the inventive concept, which is set forth in the following claims.
Claims (14)
1. A system for detecting acoustic frequency resolving power in a mouse, comprising: the system comprises an upper computer, an I/O processor and a mouse experimental box;
the upper computer is used for monitoring the experimental device, controlling the state of the I/O processor and storing experimental data;
the I/O processor is used for being connected with devices arranged inside and outside the mouse experiment box and processing data obtained by each sensor;
the mouse experiment box is a sound insulation box, and the sound insulation box internally comprises a camera, an LED lamp bead, a loudspeaker, a mouse retainer, a head retainer, a water nozzle made of a stainless steel capillary tube and a superfine optical fiber or infrared electronic geminate transistor connected with the water nozzle;
and a relay, an electromagnetic valve, an optical fiber amplifier, a medical infusion bottle and an infusion tube are arranged outside the sound insulation box.
2. The system of claim 1, wherein the I/O processor is connected to an LED light bead in the sound-proof box to form an error prompt circuit for prompting error events and missed events of the mouse during the training task;
the I/O processor is connected with the electromagnetic valve through a relay, and forms a drinking water reward circuit together with the medical transfusion bottle and the transfusion tube, and the drinking water reward circuit is used for rewarding drinking water for the mouse through the water nozzle when an avoiding and correct hitting event occurs in a training task;
the I/O processor is connected with a water nozzle in the sound insulation box through a superfine optical fiber and an optical fiber amplifier or an infrared electronic geminate transistor to jointly form a water licking sensing circuit which is used for sensing the water licking behavior of a mouse in a training task;
the I/O processor is connected with the loudspeaker to form an auditory stimulation circuit which is used for giving sound stimulation in a training task.
3. The system as claimed in claim 2, wherein the solenoid valve is installed outside the sound insulation box, the 5V high level signal output by the I/O processor is output to the relay signal end, the relay control end is connected to the solenoid valve, and the solenoid valve controls the water path formed by the medical infusion bottle and the infusion tube; the electromagnetic valve is in a normally closed state when not electrified, and after the relay is electrified, the electromagnetic valve is started, the water way is communicated, and water is supplied to the mice.
4. The system of claim 2, wherein the four types of circuit switches are controlled by an I/O processor, the I/O processor is controlled by a program of the upper computer, and the upper computer controls the entire training process by detecting the state of the I/O processor and acquiring the stored experimental data.
5. The system of claim 1, wherein the head holder is for holding a mouse head;
the mouse retainer is used for retaining a mouse so that the limb behaviors of the mouse are limited;
the superfine optical fiber is used for sensing the water licking behavior of a mouse, the optical fiber is communicated with a light path, and the blocking state of the light path can be converted into an electric signal by the optical fiber amplifier and transmitted to the I/O processor;
the optical fiber amplifier is used for processing the photosensitive signal, and light emitted by the optical fiber is converted into a continuous level signal by the optical fiber amplifier after being blocked by the mouse tongue and is transmitted back to the I/O processor;
the infrared electronic pair tube replaces an ultrafine optical fiber and an optical fiber amplifier to work independently, and senses the water licking behavior of the mouse through whether the emitted infrared light beam is blocked or not;
the water nozzle is used for supplying water to the mice in the experiment process;
the medical infusion bottle and the infusion tube are used for a drinking water waterway and are controlled by an electromagnetic valve;
the camera is used for detecting the state of the mouse;
the system also includes wires for connecting the various components of the system.
6. The system of claim 1, wherein the hardware design logic principle of the system is as follows: the auditory stimulation circuit, the licking sensing circuit, the drinking reward circuit and the error prompt circuit transmit the circuit detection results to the I/O processor hardware, the detection results of all the circuits are processed through a pre-designed I/O processor program, and the upper computer monitors the program and stores the detection data of all the circuits.
7. The system of claim 2, wherein in the licking sensing circuit, if the I/O processor and the water nozzle are connected through the ultrafine fiber and the fiber amplifier, the brightness of light blocked in the process of licking water by the tongue of the mouse is utilized and converted into an analog electric signal through the fiber amplifier, namely, the closer the tongue is to the ultrafine fiber, the larger the change of the generated analog electric signal is; the detection of the water licking behavior of the mouse is realized; if the I/O processor is connected with the water nozzle through the infrared electronic geminate transistors, the mouse tongue licks water to block infrared beams emitted by the infrared electronic geminate transistors, and the water licking process of the mouse is sensed and detected.
8. A method for detecting the acoustic frequency resolving power of a mouse using the system of any one of claims 1-7 for non-disease diagnosis or treatment purposes, the method comprising the steps of:
step one, processing an experimental mouse, and installing a fixer;
step two, performing pre-training, single-sound training and double-sound training on the treated experimental mouse in sequence, and detecting the sound discrimination threshold of the mouse;
and step three, detecting the resolving power of the experimental mouse by using the designed test tone.
9. The method of claim 8, wherein in step one, the fixture is adhered to the skull of the mouse exposed after cutting the scalp by tissue glue or 502 glue, and the wound is sutured; the fixator is used for fixing the head of a mouse.
10. The method as claimed in claim 8, wherein in the second step, the pre-training is carried out by placing a water nozzle connected with an ultra-fine optical fiber and an optical fiber amplifier or an infrared electronic pair tube near the mouth of the mouse, guiding the mouse to lick water, and entering the next stage of training after the mouse can successfully lick water 100 times.
11. The method as claimed in claim 8, wherein in the second step, the monophonic training is to stimulate the mouse with the target sound, guide the mouse to lick the water in a predetermined time window after the target sound stimulation, and enter the next training stage when the ratio of the number of times of the lick after the target sound stimulation to the total number of times reaches 70%.
12. The method according to claim 8, wherein in the second step, the binaural training is specifically to set a target sound and a non-target sound which are different in two sound frequencies, the target sound and the non-target sound are separated by 0.75-fold interval, multiple rounds of training are performed, after one round of training is performed, the proportion of the non-target sound is increased, the increase of the proportion of the non-target sound is realized by increasing the proportion of the non-target sound in random number selection by using a program, and data of each behavior of the mouse in the binaural training is recorded; the behavior of the mouse in the double-sound training comprises the following steps: water licking after target acoustic stimulation is recorded as "hit", water licking after non-target acoustic stimulation is recorded as "error", water licking without target acoustic stimulation is recorded as "avoidance", water licking without target acoustic stimulation is recorded as "miss"; calculating an expression score P from the four numbers of behavioral expressions in a fixed number of stimuli, P ═ H-H × F; wherein, H is the number of hits/number of target acoustic stimuli, and F is the number of errors/number of non-target acoustic stimuli; when the proportion of the last round of non-target sounds in the two-sound training reaches 70% and the performance score exceeds 70%, the mouse training is finished.
13. The method according to claim 8, wherein in step three, the sound frequency resolution of the mouse is detected by a plurality of test sounds with different structural sound frequencies, and the performance score P 'H' -H 'x F' of the mouse under stimulation of each sound frequency is obtained; where H 'is the number of hits/target number of acoustic stimulations, and F' is the number of frequency errors/non-target number of acoustic stimulations.
14. The method of claim 13, wherein the test tones include single frequency pure tones, repeating noise; the repeated pure tone or the repeated noise refers to a sound composed of a plurality of pure tones or noises, and the speed of sound presentation in the repeated pure tone or the repeated noise has a time phase characteristic; the test sounds including the target sound or the non-target sound include repetitive sounds of different repetition rates.
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