Multi-mode mouse virtual reality and nerve recording integrated system based on skull anchoring

Abstract

The invention belongs to the technical field of mouse neuroscience research, and relates to a multi-modal mouse virtual reality and nerve recording integrated system based on skull anchoring, which comprises a skull anchoring basic support, a binocular miniature VR display module, a multi-modal fixed expansion frame and a behavior and power supply platform. According to the invention, the skull screw is used as a unique space reference, accurate limiting of the head is realized through rapid butt joint of the MMA and the external fixing rod, and rapid plugging and coordinate multiplexing of equipment for two-photon imaging, optical genetic stimulation and the like are realized in combination with an M2 anchoring hole preset in the MMA; the total mass of the whole machine is strictly controlled within 3.2 g; the optical system provides panoramic visual stimulation with a horizontal field angle of 140 degrees, completely covers a key binocular vision area on the top of the mouse head, and supports high-order cognitive task paradigms such as complex ecological visual navigation, spatial memory and social interaction.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of mouse neuroscience research, and particularly relates to a multi-modal mouse virtual reality and neural recording integrated system based on skull anchoring, which is used for mouse neuroscience research under a state of wakefulness and free behavior or a state of head fixation. BACKGROUND

[0002] In the field of mouse neuroscience research, the application scenarios of virtual reality (VR) technology are increasingly widespread. By constructing a realistic virtual environment, researchers can simulate various natural conditions of behavior tasks to study the neural mechanisms underlying complex behaviors of mice such as spatial navigation, learning and memory, and decision making. In particular, it is of great significance to understand how the brain processes spatial information and the relationship between visual cues and motor instructions. VR technology allows scientists to precisely control experimental variables while recording the behavioral responses and corresponding neural activity patterns of mice, which is crucial for revealing the relationship between perception, cognition, and behavior.

[0003] Generally, VR research is combined with electrophysiological recording or imaging techniques to detect the activity of neurons when performing specific tasks. For example, when performing two-photon calcium imaging, it can be observed in real time which neurons in the cerebral cortex of the mouse are activated when it moves in the virtual environment, and how these activation patterns change with changes in the environment. This combination not only helps to understand the functional characteristics of individual neurons, but also helps us to understand how the entire neural network cooperates to complete complex cognitive functions. In addition, using fiber optic spectrometers or optogenetic methods, researchers can also explore the specific contribution of specific types of neurons to behavioral output at the molecular level.

[0004] The surround projection system and the head-mounted micro-display system represent two main technical routes for mouse virtual reality research. Early schemes generally use a cylindrical screen with a high-speed projector, and the mouse head is rigidly fixed above the air float ball through a metal head rod, and the visual flow is used to simulate linear track, ring path and other virtual environments. The subsequent development of spherical dome projection system (such as hemispherical or full dome) further expands the horizontal field of view to 270°, which significantly improves the sense of immersion. However, such systems rely on bulky external optical components and precisely calibrated projection light paths. Although it can coexist with a two-photon microscope in physical space, there are still multiple limitations: large equipment footprint, difficult to integrate into a compact behavior platform; only provide monocular or pseudo-stereoscopic vision, lack of real depth cues; the eye is blocked by the fixed structure, and local drug administration, lens cleaning or optometry cannot be performed; more importantly, due to the long projection distance and low pixel density, the system cannot present high spatial frequency fine visual stimuli (such as fine stripes, small size landmarks or complex textures), which limits the study of high-order encoding mechanisms of the visual cortex. These defects have promoted the rise of lightweight, high-resolution head-mounted micro-display systems.

[0005] The iMRSIV system first integrates binocular Micro-OLED display screens and custom positive meniscus lenses on a miniaturized platform, realizing high-resolution stereoscopic virtual reality with a horizontal field of view of ≥140°. However, the system still uses a whole head structure, which needs to be fixed during experiments, potentially affecting the long-term behavior of mice. More importantly, all existing head-mounted solutions have failed to resolve the fundamental contradiction between "multimodal compatibility" and "eye maintenance": once installed, it is almost impossible to perform eye drops, infrared optometry, lens cleaning or corneal monitoring without damaging the fixed state; and if repeatedly disassembled, it is easy to cause cement loosening, skin damage or optical alignment failure. In addition, these devices lack standardized mechanical and electrical interfaces, and when double-photon imaging, fiber photometry or electrophysiological probes are added, independent supports must be installed, which not only introduces mechanical redundancy and vibration noise, but also causes the coordinate systems of different modalities to be inconsistent, hindering the accurate tracking and causal intervention of neurons across days and devices.

[0006] It should be noted that the information disclosed in the above background section is only used to strengthen the understanding of the background of the present application, and therefore can include information that is not prior art known to those of ordinary skill in the art. SUMMARY

[0007] The purpose of the present application is to solve the technical problems existing in the background art. To this end, a skull-anchored multimodal mouse virtual reality and neural recording integrated system is provided.

[0008] In order to achieve the above purpose, the technical scheme adopted by the present application is as follows: A multi-modal mouse virtual reality and neural recording integrated system based on skull anchoring, comprising: A skull anchoring base support, comprising a skull screw, a nut, an adjustable ring buckle, an angle plate and a mirror frame; wherein the end surface of the skull screw is bonded to the surface of the mouse skull to form a rigid reference point; the adjustable ring buckle is sleeved on the skull screw; the adjustable ring buckle, the angle plate and the mirror frame are connected in sequence; the mirror frame is used for stably clamping a miniature optical lens to ensure that the optical axis is aligned with the pupil of the mouse; the nut is threadedly connected with the skull screw to axially lock; A binocular miniature VR display module, comprising a Micro-OLED screen, a positive meniscus lens, a display driving PCB and a flexible flat cable; wherein an external host computer sends MIPIDSI 4-lane differential signals containing a clock channel and four groups of data channels to the head-mounted module through an external interface board and a flexible flat cable, and provides a 3.3V power supply and a ground wire at the same time; the FPGA on the display driving PCB receives signals, decodes them into RGB parallel video data in real time; the Micro-OLED screen is sequentially controlled to light up corresponding pixels frame by frame to emit images; the image light emitted by the Micro-OLED screen is optically amplified and corrected by the positive meniscus lens to form a clear virtual image located 5-15 cm in front of the mouse eyes; finally, the mouse perceives the virtual reality scene with both eyes; A multi-modal fixed expansion frame, comprising a disc main body, a center positioning hole, a plurality of inner circle threaded holes and a plurality of outer circle threaded holes; wherein the geometric center of the disc main body is provided with the center positioning hole for sleeving the skull screw to realize quick alignment and reference unification; the plurality of inner circle threaded holes are uniformly distributed on the circumference with a radius of 10 mm of the disc main body for installing short force arm functional modules; the plurality of outer circle threaded holes are uniformly distributed on the circumference with a radius of 16 mm of the disc main body for installing long force arm functional modules.

[0009] The following is a further defined technical solution of the application, which also comprises a behavior and power supply platform. The behavior and power supply platform comprises an open field and a floating ball; wherein the open field is used for the mouse to walk, turn around and explore completely freely, and is matched with a high-speed infrared camera, an optical motion capture system or an embedded optical position tracking system to capture the motion trajectory of the head or body of the mouse in real time, and synchronously input the trajectory information into a virtual reality engine to dynamically update the visual scene; the floating ball is suspended by introducing compressed air at the bottom to realize the free rolling of the mouse with zero friction, and is integrated with orthogonally arranged optical encoders to detect the rotation of the ball body in X / Y two directions in real time by using an infrared grating, restore the motion trajectory and drive the virtual reality scene update.

[0010] The following is a further limited technical solution of the application, the skull screw adopts a titanium alloy material with excellent biocompatibility, a standard M3 thread is processed on the outer diameter, and is adhered to the surface of the mouse skull through a double fixation mode of dental cement and tissue glue to form a non-removable rigid reference point. The nut adopts a titanium alloy material with excellent biocompatibility, a standard M3 thread is processed on the inner diameter, and is screwed with the skull screw to realize the axial locking function, and the nut after being screwed exerts a controllable pre-tightening force on the components on the skull screw.

[0011] The following is a further limited technical solution of the application, the skull anchor base support further comprises a straight arm, an adjustable ring buckle, an angle plate, a mirror frame and a straight arm are integrally formed, wherein the adjustable ring buckle is in the shape of a circular runway, the inner ring size is 10mm*3mm, the ring width is 0.5mm, which ensures uniform stress and allows fine positioning when the nut is pressed; the angle plate allows manual bending to an angle range of 110°-150° to adapt to the head shape profile and eye socket dissection position of different strains of mice; the inner diameter of the mirror frame is 8mm, which is used to stably hold the miniature optical lens and ensure the accurate alignment of the optical axis and the mouse pupil; the four straight arms extend from the mirror frame and point to the upper left, upper right, lower left and lower right directions (corresponding angles are 45°, 45°, 135° and 135°), in a diagonal cross layout, surrounding and fixing the screen. This structure can be used with glue to stably install the lens and the screen in front of the mouse's eyes. Each arm has a certain plasticity and can be moderately bent according to the size of the individual's head, which facilitates installation while adjusting during the measurement process, ensuring that the lens and the screen maintain a proper distance.

[0012] The following is a further limited technical solution of the application, the Micro-OLED screen as a visual output unit adopts a miniature organic light-emitting diode display screen, and the light-emitting layer is directly integrated on a single crystal silicon CMOS backplane by an organic material.

[0013] The following is a further limited technical solution of the application, the focal length f of the positive meniscus lens is 7.0 mm, the diameter is 8mm, and the positive meniscus lens is double-coated with an anti-reflection film to effectively suppress surface reflection.

[0014] The following is a further limited technical solution of the application, the display driving PCB has a size of 10mm*8mm*1.6mm, integrates FPGA, power management unit and signal protection circuit, realizes local high-speed image processing and stable power supply.

[0015] The following is a further limited technical solution of the application, the flexible flat cable adopts a 12-pin interface, the length is 80 cm, is used for connecting the head-mounted module and an external computer, supports floating power supply and low tension wiring design, maximally reduces the interference on the free movement of the mouse, and simultaneously guarantees reliable transmission of high-speed video signals and power supply.

[0016] The following is a further limited technical solution of the application, the disc main body is made of biocompatible titanium alloy, the diameter is 20 mm, and the thickness is 1.5 mm.

[0017] The following is a further limited technical solution of the application, the behavior and power supply platform further comprises a pulley system and a water licking reward system; wherein the pulley system is used for suspending the flexible flat cable, maintaining slight tension of the flexible flat cable, avoiding winding, and supporting 360-degree free rotation; the water licking reward system integrates an infrared water licking sensor and an electromagnetic valve, and triggers liquid reward synchronously with a VR event.

[0018] Compared with the prior art, the application has the following technical effects: The application takes the skull screw as the only space reference, realizes accurate head limiting through rapid butt joint of the MMA and the external fixing rod, realizes rapid plugging and coordinate reuse of devices such as two-photon imaging and optical genetic stimulation in combination with the preset M2 anchor hole on the MMA, eliminates mechanical coordinate drift in cross-modal and cross-day experiments, ensures long-term tracking reliability of the same neuron cluster, strictly controls the total mass of the whole machine to be less than 3.2 grams (<10% of the weight of the mouse), is significantly lower than the animal behavior tolerance threshold, avoids increase of neck load or interference of movement coordination, and the optical system provides panoramic visual stimulation with a horizontal field angle of 140°, completely covers the key binocular zone on the top of the mouse head, and supports complex ecological visual navigation, spatial memory and social interaction and other high-order cognitive task paradigms.

[0019] The application will be further described below in combination with the drawings and embodiments. DRAWINGS

[0020] In order to more clearly illustrate the technical solutions in the embodiments of the application or the prior art, the drawings needed to be used in the embodiments or the prior art will be briefly introduced below, and obviously, the drawings in the following description are only some embodiments of the application, and other drawings can be obtained by those skilled in the art without creative labor on the basis of the drawings.

[0021] Figure 1 It is a structural schematic diagram of the skull anchoring base support in the application.

[0022] Reference numeral: 1, skull screw; 2, nut; 3, adjustable ring buckle; 4, angle plate; 5, mirror frame; 6, optical lens; 7, straight arm; 8, Micro-OLED screen. DETAILED DESCRIPTION

[0023] In order to make the above objectives, features and advantages of the present application more obvious and easy to understand, the specific embodiments of the present application will be described in detail below with reference to the accompanying drawings. In the following description, a large number of specific details are set forth in order to facilitate a full understanding of the present application. However, the present application can be implemented in many other ways different from those described herein, and those skilled in the art can make similar improvements without departing from the spirit of the present application, so the present application is not limited to the specific embodiments disclosed below.

[0024] In the description of the present application, it should be understood that the terms "upper", "lower", "front", "back", "left", "right", "vertical", "horizontal", "top", "bottom", "inner", "outer" and the like indicate the orientation or positional relationship based on the orientation or positional relationship shown in the drawings, and are only for the purpose of facilitating the description of the present application and simplifying the description, and do not indicate or imply that the device or element referred to must have a particular orientation, be constructed and operated in a particular orientation, and therefore cannot be understood as a limitation on the present application.

[0025] In the embodiments of the present application, unless otherwise explicitly specified and limited, the terms "mounting", "connection", "connection", "fixing" and the like should be understood broadly, for example, it can be fixedly connected, or it can be detachably connected, or it can be integrated; it can be mechanically connected, or it can be electrically connected; it can be directly connected, or it can be indirectly connected through an intermediate medium; it can be the internal communication of two elements or the interaction relationship between two elements. For those skilled in the art, the specific meaning of the above terms in the embodiments of the present application can be understood according to the specific circumstances.

[0026] As shown in Figure 1 The present embodiment provides a skull anchor-based multi-modal mouse virtual reality and neural recording integrated system, which is composed of four modules, namely: skull anchor-based basic support, binocular micro-VR display module, multi-modal fixed expansion rack and behavior and power supply platform (not shown in the figure).

[0027] As shown in Figure 1As shown, the skull anchoring base support includes a skull screw 1, a nut 2, and a mirror frame module (the mirror frame module is composed of an adjustable ring buckle 3, an angle plate 4, and a mirror frame 5). The skull screw 1: in order to realize long-term stable skull anchoring, the skull screw 1 adopts titanium alloy material with excellent biocompatibility, and the outer diameter is processed with standard M3 threads, which is permanently bonded to the surface of the mouse skull by double fixation of dental cement and tissue glue, forming a non-removable rigid reference point. The nut 2: made of titanium alloy of the same material, the inner diameter is processed with standard M3 threads, and is matched with the skull screw 1 in standard threads to realize the axial locking function, and after being screwed, it can exert a controllable pre-tightening force on the components on the skull screw 1. Mirror frame module (left / right): made of titanium alloy by integral molding, integrating adjustable ring buckle 3, angle plate 4 and mirror frame 5, straight arm 7 four major functional structures, the adjustable ring buckle 3 at the back end is sleeved on the skull screw 1, and is axially pressed from above by the nut 2, realizing non-rotating, high repeatability and rigid fixation. Adjustable ring buckle 3: in the shape of a circular track, the inner ring size is 10mm x 3mm, and the ring width is 0.5mm, which ensures uniform stress when the nut 2 is pressed and allows fine positioning. Angle plate 4: can be manually bent to 110°-150° to adapt to the head shape profile and anatomical position of the eye socket of different strains of mice, improving the comfort and optical alignment accuracy of wearing. Mirror frame 5: the inner diameter is about 8mm, used to firmly hold the miniature optical lens 6, and ensure the accurate alignment of the optical axis and the mouse pupil. The entire system takes the skull screw 1 as the only mechanical reference, realizes modular assembly through threaded locking, and takes into account long-term stability, individual adaptability and experimental repeatability.

[0028] The binocular micro-VR display module includes a Micro-OLED screen 8, a positive crescent lens, a display driving PCB, and a flexible flat cable. The Micro-OLED screen 8: as the core visual output unit, a micro organic light-emitting diode display screen is adopted, the light-emitting layer of which is directly integrated on a single crystal silicon CMOS backplane by organic materials, and has the advantages of self-luminous, ultra-high contrast (>100,000:1), high resolution, high refresh rate, microsecond-level response speed, etc., and can present high frame rate, low delay and immersive virtual visual stimulation. The positive crescent lens: focal length f = +7.0 mm, diameter φ8 mm, double-side anti-reflection coating, effective suppression of surface reflection, overall transmittance >99%, ensuring that the light emitted by the OLED is efficiently and clearly projected to the mouse's distance of vision (about -63 mm). The display driving PCB: the size can be reduced to 10 mm x 8 mm x 1.6 mm, and the FPGA (field programmable gate array), power management unit and signal protection circuit are highly integrated to realize local high-speed image processing and stable power supply. The flexible flat cable (FPC): a 12-pin interface is adopted, the length is 80 cm, and the connection head module and the external computer are connected, supporting floating power supply and low tension wiring design, which minimizes the interference to the free movement of the mouse, while ensuring the reliable transmission of high-speed video signals and power supply. The whole display module takes into account the optical performance, miniaturization and behavior compatibility, and is suitable for long-term and high-precision VR experiments in neuroscience.

[0029] The signal flow is as follows: the external host / upper computer (such as a computer) sends MIPI DSI 4-lane differential signals to the head-mounted module through the external interface board and the flexible flat cable, including the clock channel (CLK±) and four groups of data channels (D0± to D3±), while providing 3.3V power supply and ground (GND); the FPGA on the display driving PCB receives this high-speed serial signal and decodes it into RGB parallel video data in real time; the Micro-OLED screen 8 is controlled by the accurate timing to light up the corresponding pixels frame by frame to emit images; the image light emitted by the Micro-OLED screen 8 is optically magnified and corrected by the positive crescent lens to form a clear virtual image located about 5-15 cm in front of the mouse's eyes; finally, the mouse's eyes perceive a high-resolution (1280x720), high-refresh-rate (120 Hz), full-view (≥140°) and depth-sensing virtual reality scene.

[0030] The multi-modal fixed expansion frame (Multi-Modal Adapter, MMA) includes a disc body, a center positioning hole, 4 inner circle threaded holes and 2 outer circle threaded holes. The disc body is made of biocompatible titanium alloy, with a diameter of 20 mm and a thickness of 1.5 mm. The center positioning hole with a diameter of φ8 mm is arranged at the geometric center of the disc body, used for sleeving into the implanted skull screw to realize quick positioning and reference unification; two groups of standardized installation interfaces are also distributed on the disc body, which are the inner circle threaded holes and the outer circle threaded holes. The inner circle threaded holes are 4 M2 threaded holes, evenly distributed on the circumference of the disc body with a radius R = 10 mm, suitable for installing objective lenses, micro-LEDs and other short-force-arm functional modules; the outer circle threaded holes are 2 M2 threaded holes, distributed on the circumference of the disc body with a radius R = 16 mm, used for installing supporting VR display screens, optical fiber supports and other long-force-arm functional modules. The entire structure takes the center positioning hole as the only spatial reference, and realizes multi-device high-precision and repeatable integration and switching through the modular threaded interface.

[0031] The multi-modal fixed expansion frame is connected with the skull anchoring base support: after the adjustable ring buckle 3 at the rear end of the mirror frame module is inserted into the skull screw 1, the center positioning hole of the MMA is sleeved into the fixed skull screw 1; the nut 2 is axially compressed and fixed to realize rigid coaxial connection; external devices (such as a two-photon microscope objective lens support and an optical fiber probe clamp) are fixed to the peripheral threaded holes through M2 screws to realize multi-modal compatibility.

[0032] The behavior and power supply platform includes free motion VR and head fixed VR. The free motion VR includes an open field, allowing the mouse to walk, turn around and explore completely freely in the open field (real two-dimensional plane). The size of the open field is limited by the length of the flexible flat cable and the height of the display driving PCB. Through the top high-speed infrared camera, the optical motion capture system or the embedded optical position tracking system, the accurate motion trajectory (position, speed, orientation) of the mouse head or body is captured in real time, and the information is input into the virtual reality engine in real time, and the visual scene is dynamically updated. The complete proprioception, vestibular input and natural motion feedback are retained, which is suitable for studying ecological navigation, path integration and multi-sensory integration behavior neural mechanisms that rely on real motion. The head fixed VR includes an air floating ball. The air floating ball is suspended by introducing compressed air at the bottom to realize nearly zero friction free rolling. The mouse treads the ball surface in a rigidly fixed head state to simulate natural walking. The high-precision optical encoder is integrated and arranged orthogonally. The infrared grating is used to detect the rotation of the ball body in X / Y two directions in real time, and the angle resolution is up to 0.1°, which can accurately restore the motion trajectory and drive the virtual reality scene update. The vestibular and real displacement inputs can be effectively isolated, and only the visual and foot proprioception are retained.

[0033] In both free movement VR and head-fixed VR modules, there are pulley systems and water licking reward systems. The flexible cable is suspended by the pulley system to maintain a slight tension (<0.3 gf) to avoid entanglement and support 360° free rotation. The water licking reward system integrates an infrared water licking sensor and a solenoid valve, which can trigger liquid rewards synchronously with VR events (such as reaching the target position).

[0034] In summary, 1. The dual experimental paradigm of the skull-anchored base support supports: (1) Basic function: The support structure can stably position the miniature lens in front of the mouse eye, integrate with components such as Micro-OLED screens and inertial sensors, and realize high-fidelity visual presentation and behavior recording in a free movement state; (2) Upgrade function: ① Head rigid fixation mode: Use skull screws as the only spatial reference, quickly connect with external fixation rods through MMA to achieve precise head positioning; On this basis, use a spherical treadmill to replace the free movement field, effectively isolate non-visual cues such as vestibular and proprioceptive cues, and thus focus on visual-driven neural coding research, suitable for high spatial accuracy experiments such as hippocampal place cell encoding mechanism; ② Multi-modal longitudinal tracking mode: Combined with the pre-set M2 anchor hole on the MMA, realize the quick plugging and coordinate reuse of two-photon imaging and optogenetic stimulation devices, eliminate mechanical coordinate drift in cross-modal and cross-day experiments, and ensure the reliability of long-term tracking of the same neuron cluster.

[0035] 2. Human-machine engineering lightweight adaptation: The total weight of the whole machine is strictly controlled within 3.2 grams (<10% of the weight of the mouse), which is significantly lower than the animal behavior tolerance threshold, avoiding increased neck load or motion coordination interference, and ensuring the ecological effectiveness of natural behaviors such as free movement, social interaction, and exploration.

[0036] 3. Geometric optical precise imaging: The actual display area of the miniature OLED display screen matches the size of the positive meniscus lens. When the screen is placed about 6.3 mm in front of the positive meniscus lens with a focal length f = +7.0 mm, according to the lens formula: 1 / f = 1 / u + 1 / v v≈ 63 mm, the lens can clearly project the image to a virtual image distance v ≈ -63 mm, which accurately matches the mouse's best distance range for clear vision (5-15 cm), ensuring that the visual stimulus is clearly focused within the natural gaze range, and improving the validity of the behavior task.

[0037] 4. Neuroscientific-driven field of view coverage: The optical system provides panoramic visual stimulation with a horizontal field of view angle of up to 140°, fully covering the key binocular vision zone on the top of the mouse's head, supporting complex ecological visual navigation, spatial memory, and social interaction, and other high-order cognitive task paradigms.

[0038] Therefore, the following advantages are provided: 1. Ultra-lightweight: VR module <1.5g, entire system <3.2g; 2. Ultra-high stability: skull direct anchoring, micron-level rigidity; 3. Full field of view immersion: FOV ≥ 140°, supporting stereoscopic vision; 4. Multi-modal compatibility: one-key switching of VR / imaging / epileptiform; 5. Convenient operation: nut quick release, single person completes eye cleaning, drug administration, and optometry; 6. Low cost: most components can be 3D printed or commercially purchased; 7. Long-term usability: dental cement fixation, supporting >8 weeks of experiments.

[0039] 8. Multi-mode switching: supporting flexible switching between fixed and non-fixed head position modes.

[0040] The working process of the embodiment will be further described as follows: 1. Installation of the skull top support: adult C57BL / 6 mice are selected for the experiment, and after anesthesia, they are fixed on a stereotaxic instrument. A longitudinal incision about 1 cm long is made along the midline of the skull, and the subcutaneous tissue is bluntly separated to fully expose the anterior fontanel and the skull surface. The skull is gently polished to be translucent with a micro drill bit, avoiding damage to the dura mater. The skull anchor base support is installed in advance, the multi-modal fixation extension is added, the skull screw 1 is accurately positioned at the position 2.0 mm behind the anterior fontanel and on the midline, and the dental cement is combined with the biocompatible tissue glue to firmly bond it to the skull, ensuring that the screw is vertical and not loose. The preparation of the skull window, the implantation of the brain electrode, the implantation of the optical fiber, and the like required in subsequent behavioral experiments or imaging experiments are simultaneously completed in this step. After complete hemostasis, antibiotic ointment is applied locally. Postoperative analgesia and warming care are given, and the mice are single-caged for recovery for at least 7 days. After the inflammation subsides and the screw is completely stable, subsequent device installation or behavioral experiments are performed. Figure 1

[0041] ​2. VR module assembly: weld the Micro-OLED screen to the corresponding pads on the display drive PCB, ensuring reliable connection of the MIPI signal and power supply; then, coaxially embed the positive meniscus lens into the mirror frame inner hole, and use low-shrinkage, high-transmittance ultraviolet curing glue (UV glue) for dispensing fixation, and after UV light irradiation, realize the rigid positioning of the optical element; then, embed the assembly of the integrated Micro-OLED and PCB into the reserved cavity groove of the titanium alloy mirror frame module, ensuring that the optical axis is aligned with the center of the mirror frame; finally, connect one end of the flexible flat cable to the display drive PCB by hot pressing or soldering, and the other end is led out and soldered to the external interface board, which is used for transmitting video signals, power supply and control commands. The entire assembly process is completed under microscopic operation, ensuring miniaturization, high precision and long-term mechanical stability. The equipment can be recycled.

[0042] 3. System assembly: manually bend the angle plate 4 of the left and right mirror frame modules to 110°-150°, so that the built-in lens optical axis is accurately aligned with the mouse's bilateral pupils; connect the end of the flexible flat cable (FPC) to the external interface board to complete the establishment of the video signal and power supply path, and the system can enter the VR display working state.

[0043] 4. Behavior training: 3 days before the experiment, gently fix the mouse on the head fixing support every day, and make it stand on the air floating spherical body, adapt for 30 minutes each time, to be familiar with the wearing feeling of the system, the feedback of the spherical body rolling and the virtual visual environment; During this period, no task is presented, only static or slow moving visual scenes are played, to help the animals establish the motion-visual association and reduce stress. From the 4th day, the virtual reality behavior task (such as linear track navigation, T-shaped maze or open field exploration) developed based on the virtual reality engine (such as Unity engine) is formally run, and the mouse controls the virtual position by stepping on the spherical body, and the system synchronously records the behavior trajectory and neural activity, realizing high-precision closed-loop experiment.

[0044] The above is only a preferred embodiment of the present application, and does not limit the present application in any form. Any person skilled in the art can make many possible changes and modifications to the technical solution of the present application, or modify it into equivalent embodiments without departing from the scope of the technical solution of the present application, using the disclosed methods and technical contents. Therefore, any equivalent changes made according to the shape, structure and principle of the present application, without departing from the technical solution of the present application, should be covered by the protection scope of the present application.

Claims

1. A multimodal mouse virtual reality and neural recording integrated system based on skull anchoring, characterized in that, It comprises: A skull anchor base support, including a skull screw, a nut, an adjustable ring buckle, an angle plate and a mirror frame; wherein the end surface of the skull screw is bonded to the surface of the mouse skull to form a rigid reference point; the adjustable ring buckle is sleeved on the skull screw; the adjustable ring buckle, the angle plate and the mirror frame are connected in sequence; the mirror frame is used to stably hold a miniature optical lens and ensure that the optical axis is aligned with the mouse pupil; the nut is threadedly connected with the skull screw to axially lock; A binocular miniature VR display module, including a Micro-OLED screen, a positive meniscus lens, a display driving PCB and a flexible flat cable; wherein an external host / upper computer sends MIPI DSI 4-lane differential signals to the head-mounted module through an external interface board and the flexible flat cable, including a clock channel and four groups of data channels, while providing 3.3V power supply and ground; the FPGA on the display driving PCB receives the signals, decodes them into RGB parallel video data in real time; the Micro-OLED screen is sequentially controlled to light up corresponding pixels frame by frame to emit images; the image light emitted by the Micro-OLED screen is optically amplified and corrected by the positive meniscus lens to form a clear virtual image located 5-15 cm in front of the mouse eyes; finally, the mouse perceives the virtual reality scene with both eyes; A multi-modal fixed expansion frame, including a disc main body, a center positioning hole, a plurality of inner circle threaded holes and a plurality of outer circle threaded holes; wherein the geometric center of the disc main body is provided with the center positioning hole for sleeving the skull screw to realize quick alignment and reference unification; the plurality of inner circle threaded holes are uniformly distributed on the circumference with a radius of 10 mm of the disc main body for installing short force arm functional modules; the plurality of outer circle threaded holes are uniformly distributed on the circumference with a radius of 16 mm of the disc main body for installing long force arm functional modules.

2. The skull-anchored multi-modal mouse virtual reality and neural recording integrated system of claim 1, wherein, It also comprises: A behavior and power supply platform; The behavior and power supply platform comprises an open field and a floating ball; wherein the open field is used for the mouse to walk, turn around and explore completely freely, and is matched with a high-speed infrared camera, an optical motion capture system or an embedded optical position tracking system to capture the motion trajectory of the mouse head or body in real time, and synchronously input the trajectory information into a virtual reality engine to dynamically update the visual scene; the floating ball is suspended by introducing compressed air at the bottom to realize the free rolling of the mouse with zero friction, and is integrated with orthogonally arranged optical encoders to detect the rotation of the ball body in X / Y two directions in real time by using an infrared grating, restore the motion trajectory and drive the virtual reality scene update.

3. The skull-anchored multi-modal mouse virtual reality and neural recording integrated system of claim 1, wherein, The skull screw is made of titanium alloy material with excellent biocompatibility, and the outer diameter is processed with standard M3 threads, which is bonded to the surface of the mouse skull by double fixation of dental cement and tissue glue to form a non-removable rigid reference point; The nut is made of titanium alloy material with excellent biocompatibility, and the inner diameter is processed with standard M3 threads, which is threadedly connected with the skull screw to realize the axial locking function, and the nut is tightened to apply a controllable pre-tightening force to the components on the skull screw.

4. The skull-anchored multi-modal mouse virtual reality and neural recording integrated system of claim 1, wherein, The skull anchoring base support further comprises a straight arm, an adjustable ring buckle, an angle plate, a mirror frame and the straight arm are integrally formed, wherein the adjustable ring buckle is in a ring runway shape, the inner ring size is 10mm*3mm, the ring width is 0.5mm, the uniform stress is ensured when the nut is pressed, and fine positioning is allowed; the angle plate is allowed to be manually bent to an angle range of 110°-150° to adapt to the head shape contour and orbital anatomical position of different mouse strains; the mirror frame has an inner diameter of 8mm, is used for firmly clamping a miniature optical lens, and ensures accurate alignment of the optical axis and the mouse pupil; four straight arms extend from the mirror frame and respectively point to the upper left, upper right, lower left and lower right directions, are arranged in a diagonal cross shape, surround and fix the screen.

5. The skull-anchored multi-modal mouse virtual reality and neural recording integrated system of claim 1, wherein, The micro-OLED screen is used as a visual output unit, and a micro organic light-emitting diode display screen is adopted, and an organic material is directly integrated on a single crystal silicon CMOS back plate to form a light-emitting layer.

6. The skull-anchored multi-modal mouse virtual reality and neural recording integrated system of claim 1, wherein, The focal length f of the positive meniscus lens is 7.0 mm, the diameter is 8 mm, and the positive meniscus lens is double-sided coated with an anti-reflection film to effectively suppress surface reflection.

7. The skull-anchored multi-modal mouse virtual reality and neural recording integrated system of claim 1, wherein, The display driving PCB has a size of 10mm*8mm*1.6mm, integrates an FPGA, a power management unit and a signal protection circuit, realizes localized high-speed image processing and stable power supply.

8. The skull-anchored multi-modal mouse virtual reality and neural recording integrated system of claim 1, wherein, The flexible flat cable adopts a 12-pin interface and has a length of 80 cm, is used for connecting the head-mounted module and an external computer, supports floating power supply and low-tension wiring design, minimizes the interference on the free movement of the mouse, and guarantees reliable transmission of high-speed video signals and power supply.

9. The skull-anchored multi-modal mouse virtual reality and neural recording integrated system of claim 1, wherein, The disc main body is made of biocompatible titanium alloy, has a diameter of 20mm and a thickness of 1.5mm.

10. The skull-anchored multi-modal mouse virtual reality and neural recording integrated system of claim 2, wherein, The behavior and power supply platform further comprises a pulley system and a water licking reward system; wherein the pulley system is used for suspending the flexible flat cable, maintaining slight tension of the flexible flat cable, avoiding winding and supporting 360° free rotation; the water licking reward system integrates an infrared water licking sensor and an electromagnetic valve, and triggers liquid reward synchronously with the VR event.

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