Mouse multi-modal stimulation and whole brain recording method, device and equipment and storage medium

Abstract

The invention provides a mouse multi-modal stimulation and whole-brain recording method, device and equipment and a storage medium, the method is applied to a mouse multi-modal stimulation and whole-brain recording platform, and the method comprises the following steps: fixing a mouse in the center of the platform, and adjusting a modular support system and a closed sound insulation shell system; receiving all stimulation trigger signals and recording sampling clocks of all devices through a synchronous control system; responding to all the stimulation trigger signals, and synchronously starting a multi-mode stimulation subsystem according to a preset normal form; neural activity data, including a calcium signal, a pupil change signal, a running speed and an electrode signal, of a mouse are collected through a multi-modal recording subsystem; and receiving the data through the synchronous control system, aligning a data time sequence, labeling a uniform timestamp, and writing the data with the aligned timestamp into the standardized container. The invention provides an efficient platform and method capable of providing multi-modal stimulation and recording whole-brain multi-modal neural activities.

Description

Technical Field

[0001] This invention relates to the field of neurological signal processing technology, and in particular to a method, apparatus, device, and storage medium for multimodal stimulation and whole-brain recording in mice. Background Technology

[0002] With the continuous development of neuroscience, research on the function and structure of the mouse brain has gradually become a hot topic, especially considering the similarity between the function and structure of the mouse brain and the human brain. This similarity makes mice an ideal model for studying brain function and disease mechanisms.

[0003] In recent years, whole-brain calcium imaging technology has matured significantly, providing a powerful tool for studying integrated multisensory stimuli. This comprehensive research aims to reveal how the brain integrates and processes information when receiving multiple sensory inputs. More importantly, this research can help us more accurately simulate and modulate the sensory stimuli experienced by mice in real-world environments.

[0004] Nevertheless, most current research relies on single stimulation patterns. This means that most studies focus only on the brain's response to specific sensory inputs, lacking a comprehensive approach to simultaneously study the effects of multiple sensory inputs on the brain. Furthermore, current research techniques often cannot record whole-brain activity in mice in real time, which to some extent limits our comprehensive understanding of brain function.

[0005] Therefore, there is an urgent need for an efficient platform and method that can provide multimodal stimulation and record multimodal neural activity throughout the brain. This would not only help to understand brain function more deeply, but also provide more sophisticated technical means for neuroscience research. Summary of the Invention

[0006] To address the aforementioned shortcomings in existing technologies, this invention provides a method, apparatus, device, and storage medium for multimodal stimulation and whole-brain recording in mice. It offers an efficient platform and method that can provide multimodal stimulation and record multimodal neural activity of the whole brain, which helps to understand brain function more deeply and provides a more complete technical means for neuroscience research.

[0007] In a first aspect, the present invention provides a method for mouse multimodal stimulation and whole-brain recording, which is applied to a mouse multimodal stimulation and whole-brain recording platform, the mouse multimodal stimulation and whole-brain recording platform comprising a soundproof shell system, a modular scaffold system, a multimodal stimulation subsystem, a multimodal recording subsystem, and a synchronization control system; the method comprises the following steps: The mouse is fixed in the center of the mouse multimodal stimulation and whole brain recording platform. The modular support system is adjusted so that each device meets the preset spatial position relationship. The soundproof shell system is closed and the sealing ring is activated to isolate external noise. The multi-functional I / O device in the synchronous control system receives all stimulus trigger signals and records the sampling clocks of all devices. In response to all the stimulus trigger signals, the multimodal stimulation subsystem is synchronously activated according to a preset paradigm; the multimodal stimulation subsystem is used to simultaneously apply visual stimulation, auditory stimulation, whisker stimulation, licking device stimulation and electrical stimulation to the mouse; The neural activity data of the mouse was acquired using the multimodal recording subsystem; the neural activity data included calcium signals, pupillary change signals, running speed, and electrode signals. The synchronous control system receives all stimulus trigger signals and the neural activity data of the mouse, aligns the timing of all stimulus trigger signals and the neural activity data of the mouse and marks them with a unified timestamp, and writes the timestamp-aligned stimulus parameters and the neural activity data into an NWB or HDF5 standardized container through the multi-functional IO device.

[0008] According to the present invention, a method for multimodal stimulation and whole-brain recording of mice is provided. The multimodal stimulation subsystem includes a programmable visual screen located 10 cm to the side of the target brain region of the mouse and at the level of both eyes, a dual-channel speaker symmetrically arranged 10 cm from the ear of the mouse, a beard stimulator located 2 to 3 cm below the face, an adjustable licking device located 5 cm in front and below, and a multi-channel electrical stimulation electrode array integrated into the head of the mouse. The response to all stimulus trigger signals, synchronously activating the multimodal stimulation subsystem according to a preset paradigm, includes: The motion parameters of the visual stimulus are dynamically adjusted within a preset range according to the program instructions, and the start and end times of the visual stimulus are controlled by the trigger output module in the synchronization control system so that the visual stimulus is synchronized with the exposure signal of the pupil recording camera; the motion parameters include the brightness, color and motion mode of the programmable visual screen; The dual-channel audio system generates a directional sound source of 20 Hz to 32 kHz, and the dual-channel delay is calibrated by the synchronous control system to ensure that the sound waves arrive at the ear canal simultaneously. Based on the event triggering mode, the visual stimulus is linked to generate a composite sensory input. Airflow stimulation is applied with an accuracy of ±0.5 mm using the beard stimulator, which is a miniature pneumatic nozzle; the nozzle angle of the miniature pneumatic nozzle is dynamically adjusted according to the mouse's head posture to maintain a constant stimulation target position. The channel mapping data of the multi-channel electrostimulation electrode array is invoked, and an adjustable current is output in a space-time encoding mode.

[0009] According to the present invention, a method for multimodal stimulation and whole-brain recording of mice is provided, wherein the multimodal recording subsystem includes a scanning light field calcium imaging device vertically aligned with the mouse head, a pupil recording camera located 10-15 cm above a programmable visual screen, and a running speed sensor at the bottom of the platform. The acquisition of neural activity data from the mouse via the multimodal recording subsystem includes: The calcium signal is obtained by tracking the mouse head movement in real time using the scanning light field calcium imaging device; the scanning light field calcium imaging device integrates wide field imaging technology and dynamic focusing module; The pupil change signal is obtained by using a near-infrared light source in the pupil recording camera to assist eye tracking, and the pupil change signal is correlated with the visual stimulus timestamp to calculate the visual response delay; the pupil change signal represents pupil diameter change data. The running speed of the mouse is collected using the running speed sensor. The electrode signals fed back from the multi-channel electrical stimulation electrode array are acquired in real time.

[0010] According to the present invention, a method for multimodal stimulation and whole-brain recording in mice includes a synchronization control system comprising a multifunctional I / O device, a trigger output module, and a signal processing program. The method involves receiving all stimulus trigger signals and neural activity data of the mouse through the synchronization control system, aligning the timing of all stimulus trigger signals and the neural activity data of the mouse and marking them with a unified timestamp, and writing the timestamp-aligned stimulus parameters and the neural activity data into an NWB or HDF5 standardized container via the multifunctional I / O device. The multi-functional I / O device is used to receive the calcium signal, pupil change signal, running speed, and electrode signal of the mouse. The trigger output module uses a ring buffer mechanism to align the timing of the stimulation parameters with the calcium signal, the pupil change signal, the running speed, and the electrode signal according to the sampling clock of all devices, and marks them with a unified timestamp. The time-stamp-aligned stimulation parameters, along with the calcium signal, pupillary change signal, running speed, and electrode signal, are written into the NWB or HDF5 normalized container using the signal processing program.

[0011] According to the present invention, a method for multimodal stimulation and whole-brain recording in mice is provided, the method further comprising: When the imaging frame drop corresponding to the calcium signal is detected, the stimulation sequence is automatically paused and data re-acquisition is triggered. The motion parameters of the visual stimulus are adjusted in real time based on the running speed.

[0012] According to the present invention, a method for multimodal stimulation and whole-brain recording in mice is provided, the method further comprising: The stimulation parameters, device response logs, and raw neural signals are stored in the NWB or HDF5 standardized container. Based on the stimulation parameters, the device response logs, and the original neural signals, a metadata index is generated that allows for the reproducibility of the experimental procedure.

[0013] Secondly, the present invention also provides a mouse multimodal stimulation and whole-brain recording device, which is applied to a mouse multimodal stimulation and whole-brain recording platform. The mouse multimodal stimulation and whole-brain recording platform includes a soundproof shell system, a modular support system, a multimodal stimulation subsystem, a multimodal recording subsystem, and a synchronization control system. The device includes: The initialization and startup module is used to fix the mouse in the center of the mouse multimodal stimulation and whole brain recording platform, adjust the modular support system so that each device meets the preset spatial position relationship, close the soundproof shell system, and activate the sealing ring to isolate external noise. The receiving module is used to receive all stimulus trigger signals and record the sampling clocks of all devices through the multi-functional IO device in the synchronization control system; A multimodal stimulation application module is used to synchronously activate the multimodal stimulation subsystem according to a preset paradigm in response to all the stimulation trigger signals; the multimodal stimulation subsystem is used to simultaneously apply visual stimulation, auditory stimulation, whisker stimulation, licking device stimulation and electrical stimulation to the mouse. The recording module is used to collect neural activity data of the mouse through the multimodal recording subsystem; the neural activity data includes calcium signals, pupillary change signals, running speed, and electrode signals. The signal synchronization control module is used to receive all the stimulus trigger signals and the neural activity data of the mouse through the synchronization control system, align the timing of all the stimulus trigger signals and the neural activity data of the mouse and mark them with a unified timestamp, and write the timestamp-aligned stimulus parameters and the neural activity data into an NWB or HDF5 standardized container through the multi-functional IO device.

[0014] Thirdly, the present invention also provides an electronic device, including a memory, a processor, and a computer program stored in the memory and executable on the processor, wherein the processor executes the computer program to implement the mouse multimodal stimulation and whole-brain recording method as described above.

[0015] Fourthly, the present invention also provides a non-transitory computer-readable storage medium having a computer program stored thereon, which, when executed by a processor, implements the mouse multimodal stimulation and whole-brain recording method as described above.

[0016] Fifthly, the present invention also provides a computer program product, including a computer program that, when executed by a processor, implements the mouse multimodal stimulation and whole-brain recording method as described above.

[0017] This invention provides a method, apparatus, device, and storage medium for mouse multimodal stimulation and whole-brain recording. The method is applied to a mouse multimodal stimulation and whole-brain recording platform, which includes a soundproof shell system, a modular support system, a multimodal stimulation subsystem, a multimodal recording subsystem, and a synchronization control system. First, the mouse is fixed in the center of the mouse multimodal stimulation and whole-brain recording platform. The modular support system is adjusted to ensure that each device meets a preset spatial positional relationship. The soundproof shell system is closed, and the sealing ring is activated to isolate external noise. All stimulus trigger signals and the sampling clocks of all devices are received through the multifunctional I / O device in the synchronization control system. Then, in response to all stimulus trigger signals... The trigger signal activates the multimodal stimulation subsystem synchronously according to a preset paradigm. This subsystem simultaneously applies visual, auditory, whisker, water-licking device, and electrical stimuli to the mouse. Further, the multimodal recording subsystem collects neural activity data from the mouse, including calcium signals, pupillary changes, running speed, and electrode signals. Then, the synchronous control system receives all the trigger signals and the mouse's neural activity data, aligns the timing of all the trigger signals and the neural activity data, and marks them with a unified timestamp. The timestamp-aligned stimulation parameters and neural activity data are then written into an NWB or HDF5 standardized container via a multi-functional I / O device.

[0018] This invention provides an efficient platform and method that can provide multimodal stimulation and record multimodal neural activity of the whole brain, which helps to understand brain function more deeply and also provides a more complete technical means for neuroscience research. Attached Figure Description

[0019] To more clearly illustrate the technical solutions in this invention or the prior art, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are some embodiments of this invention. For those skilled in the art, other drawings can be obtained from these drawings without creative effort.

[0020] Figure 1This is a flowchart illustrating the mouse multimodal stimulation and whole-brain recording method provided by the present invention.

[0021] Figure 2 This is a schematic diagram of the structure of the mouse multimodal stimulation and whole-brain recording platform provided by the present invention.

[0022] Figure 3 This is a structural schematic diagram of the soundproof shell system provided by the present invention.

[0023] Figure 4 This is a schematic diagram of the structure of the mouse multimodal stimulation and whole-brain recording device provided by the present invention.

[0024] Figure 5 This is a schematic diagram of the structure of the electronic device provided by the present invention. Detailed Implementation

[0025] To make the objectives, technical solutions, and advantages of this invention clearer, the technical solutions of this invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some, not all, of the embodiments of this invention. All other embodiments obtained by those skilled in the art based on the embodiments of this invention without creative effort are within the scope of protection of this invention.

[0026] The following is combined Figures 1-5 The present invention describes a method, apparatus, device, and storage medium for mouse multimodal stimulation and whole-brain recording.

[0027] Figure 1 This is a flowchart illustrating the mouse multimodal stimulation and whole-brain recording method provided by the present invention. This method is applied to a mouse multimodal stimulation and whole-brain recording platform, which includes a soundproof shell system, a modular scaffold system, a multimodal stimulation subsystem, a multimodal recording subsystem, and a synchronization control system. Figure 1 As shown, the method includes the following: Step 101: Fix the mouse in the center of the mouse multimodal stimulation and whole brain recording platform, adjust the modular support system to make each device meet the preset spatial position relationship, close the soundproof shell system, and activate the sealing ring to isolate external noise.

[0028] It should be noted that the subject of this invention is a mouse multimodal stimulation and whole-brain recording platform, which is an efficient platform and method for providing multimodal stimulation and recording multimodal neural activity of the whole brain.

[0029] The mouse multimodal stimulation and whole-brain recording platform comprises a soundproof shell system, a modular support system, a multimodal stimulation subsystem, a multimodal recording subsystem, and a synchronization control system. The soundproof shell system consists of a DAQ-type piston seal and a PET / polyurethane / asbestos soundproof enclosure. The modular support system uses vibration-damping materials and precision adjustment mechanisms to secure all equipment and maintain stable spatial relationships. The multimodal stimulation subsystem applies multimodal stimulation to mice, including visual stimulation, auditory stimulation, whisker stimulation, electrical stimulation, and a licking device. The multimodal recording subsystem records multimodal whole-brain neural data. The synchronization control system integrates multifunctional input / output (IO) devices for receiving digital / analog signals from the stimulation and recording devices, a trigger output module that generates synchronization pulses based on a preset timeline or external events, and signal processing programs for signal buffering, timestamp alignment, frame drop detection, and data storage, achieving millisecond-level synchronization across devices.

[0030] For example, Figure 2 This is a schematic diagram of the structure of the mouse multimodal stimulation and whole-brain recording platform provided by the present invention, as shown below. Figure 2 As shown, the mouse multimodal stimulation and whole-brain recording platform includes a multimodal stimulation subsystem and a multimodal recording subsystem. The multimodal stimulation subsystem includes: b. visual stimulation (device), c. auditory stimulation (device), d. whisker stimulation (device), e. licking water (device), f. electrode stimulation and recording. The multimodal recording subsystem includes: a. whole-brain calcium imaging (device), h. treadmill.

[0031] A mouse multimodal stimulation and whole-brain recording method based on this platform includes platform initialization and soundproof environment startup, multimodal stimulation application, synchronous recording of whole-brain data, closed-loop signal synchronous control, and data integration and storage.

[0032] The platform initialization and soundproof environment startup process includes the following steps: The mouse was fixed in the center of the mouse multimodal stimulation and whole-brain recording platform. The modular scaffold system was adjusted to ensure that each device met the preset spatial positional relationship. The soundproof shell system was closed, and the sealing ring was activated to isolate external noise. The devices included, for example: a. whole-brain calcium imaging (device), b. visual stimulation (device), c. auditory stimulation (device), d. whisker stimulation (device), e. licking water (device), f. electrode stimulation and recording, and h. a treadmill.

[0033] In experiments involving mice with fixed heads, recording methods based on wide-field imaging systems have been widely adopted. However, this method still faces some technical challenges. For example, in experiments involving auditory stimulation, laboratories typically need to invest heavily in building soundproof rooms or using simple soundproofing materials, but the latter often cannot completely isolate noise due to the characteristics of microscopes. To address the noise interference problem in conventional laboratory environments, this platform employs a sound-insulating shell. Figure 3 This is a structural schematic diagram of the soundproof enclosure system provided by the present invention, as shown below. Figure 3 As shown, the closed soundproof enclosure system of this invention includes a sealing ring, an objective lens, and an acoustic panel, used to isolate external noise during experiments. The sealing ring, utilizing a DAQ-type piston seal, ensures that external noise will not interfere with the experiment. The material of the acoustic panel can be selected according to the specific needs of the experiment, such as PET, rigid polyurethane foam, or asbestos.

[0034] To ensure the accuracy and recording efficiency of multimodal stimulation, this platform features a spatially optimized layout of various stimulation devices and recording instruments. Mice are fixed in the center of a running ball or track, with their heads secured to the platform center using a head cap. Each stimulation device is spatially aligned according to the mouse's sensory distribution and stimulation pathways: the visual stimulation device is located 10 cm to the side of the target brain region, displaying visual images via an LCD or OLED screen at eye level, supporting multi-directional pattern movements; auditory stimulation devices are symmetrically positioned approximately 10 cm from the ear to the side of the target brain region, ensuring sound enters simultaneously from the lateral ear canal and avoiding perceptual deviation due to sound source offset; whisker stimulators (e.g., airflow or miniature robotic arms) are positioned approximately 2-3 cm below and to the sides of the mouse's face, angled slightly upwards, to simulate tactile stimulation in the natural environment; a licking device is installed 5 cm below and to the front of the mouse, with an adjustable position to match the mouse's natural tongue extension trajectory, combined with infrared sensing and metering feedback; electrical stimulation devices are generally integrated into the small... In the electrode system pre-implanted in the mouse's head or body, local current is transmitted through preset programs and channels; the pupil recording camera is located directly above or slightly above the visual stimulation screen, 10-15 cm away from the mouse's eyes, and is equipped with a near-infrared light source to assist tracking; the calcium signal recording device (such as the RUSH imaging system) is vertically mounted directly above the mouse's head, with the imaging lens aimed at the brain surface, and dynamically focused using a scanning light field system; the running speed recording device can be a float, pulley, or tracked system, installed at the bottom of the platform, and records motion data in real time through encoders or photoelectric sensors; all devices are embedded or suspended in a modular platform support system through independent modules, the support is made of vibration-damping material, and a precision adjustment mechanism ensures that all stimuli and recording units maintain a stable and consistent relative spatial relationship.

[0035] Step 102: Receive all stimulus trigger signals and record the sampling clocks of all devices through the multi-functional IO device in the synchronous control system.

[0036] Specifically, the initialization process also includes closed-loop signal synchronization control. For example, the multi-functional IO device in the synchronization control system receives all stimulus trigger signals and records the sampling clocks of all devices, which facilitates data timing alignment during subsequent data storage.

[0037] Step 103: In response to all stimulus trigger signals, the multimodal stimulation subsystem is started synchronously according to the preset paradigm; the multimodal stimulation subsystem is used to simultaneously apply visual stimulation, auditory stimulation, whisker stimulation, licking device stimulation and electrical stimulation to the mouse.

[0038] Specifically, multimodal stimulation is applied through the following steps: receiving stimulus trigger signals and outputting whole-brain recording data are achieved through a multifunctional I / O device; in response to all stimulus trigger signals, the multimodal stimulation subsystem is synchronously activated according to a preset paradigm. The multimodal stimulation subsystem is used to simultaneously apply visual, auditory, whisker, water-licking device, and electrical stimuli to the mouse.

[0039] Step 104: Collect neural activity data of mice through the multimodal recording subsystem; neural activity data includes calcium signals, pupillary change signals, running speed and electrode signals.

[0040] Specifically, after applying multimodal stimulation to mice, neural activity data of the mice are simultaneously acquired through a multimodal recording subsystem. The multimodal recording subsystem may include, for example, a calcium signal recording device (such as a RUSH imaging system), a velocity sensor, and a pupil camera.

[0041] The collected neural activity data, including calcium signals, pupillary change signals, running speed, and electrode signals, can better record the mouse's response to multimodal stimulation.

[0042] Step 105: Receive all stimulus trigger signals and mouse neural activity data through the synchronous control system, align the timing of all stimulus trigger signals and mouse neural activity data and mark them with a unified timestamp, and write the timestamp-aligned stimulus parameters and neural activity data into an NWB or HDF5 standardized container through a multi-functional IO device.

[0043] Specifically, the synchronization control system includes: a multi-functional I / O device that receives digital / analog signals from the stimulation and recording devices; a trigger output module that generates synchronization pulses based on a preset timeline or external events; and a LabVIEW or Python program module that performs signal buffering, timestamp alignment, frame drop detection, and data storage.

[0044] The closed-loop signal synchronization control steps include the following: The system receives all stimulus trigger signals and mouse neural activity data through a synchronous control system. Then, it aligns the timing of all stimulus trigger signals and mouse neural activity data and marks them with a unified timestamp. Furthermore, the timestamp-aligned stimulus parameters and neural activity data are written into a Neurodata Without Borders (NWB) or Hierarchical DataFormat version 5 (HDF5) standardized container through a multi-functional IO device.

[0045] NWB and HDF5 are both powerful container formats for managing and storing complex scientific data. HDF5 is a general-purpose, open-source, high-performance file format and library for storing and managing large amounts of complex, heterogeneous scientific data. HDF5 is a domain-specific data standard, software library, and file format based on HDF5, designed specifically for storing and sharing neurophysiological data, especially electrophysiological and behavioral data.

[0046] The method provided in this embodiment is applied to a mouse multimodal stimulation and whole-brain recording platform. The mouse multimodal stimulation and whole-brain recording platform includes a soundproof shell system, a modular support system, a multimodal stimulation subsystem, a multimodal recording subsystem, and a synchronization control system. First, the mouse is fixed in the center of the mouse multimodal stimulation and whole-brain recording platform. The modular support system is adjusted to ensure that each device meets a preset spatial positional relationship. The soundproof shell system is closed, and the sealing ring is activated to isolate external noise. All stimulus trigger signals and the sampling clocks of all devices are received through the multifunctional I / O device in the synchronization control system. Then, in response to all stimulus trigger signals, the system synchronizes the recording according to a preset paradigm. The first step involves activating the multimodal stimulation subsystem, which simultaneously applies visual, auditory, whisker, water-licking device, and electrical stimuli to mice. Further, a multimodal recording subsystem collects neural activity data from the mice, including calcium signals, pupillary changes, running speed, and electrode signals. Then, a synchronous control system receives all stimulus trigger signals and the mice's neural activity data, aligns the timing of all stimulus trigger signals and the mice's neural activity data, and assigns a unified timestamp. The timestamp-aligned stimulus parameters and neural activity data are then written into an NWB or HDF5 standardized container via a multifunctional I / O device.

[0047] This invention provides an efficient platform and method that can provide multimodal stimulation and record multimodal neural activity of the whole brain, which helps to understand brain function more deeply and also provides a more complete technical means for neuroscience research.

[0048] According to the present invention, a method for multimodal stimulation and whole-brain recording of mice is provided. The multimodal stimulation subsystem includes a programmable visual screen located 10 cm to the side of the target brain region of the mouse and at the level of both eyes, a dual-channel speaker symmetrically arranged 10 cm from the ear of the mouse, a beard stimulator located 2 to 3 cm below the face, an adjustable licking device located 5 cm in front and below, and a multi-channel electrical stimulation electrode array integrated into the head of the mouse. In response to all stimulus trigger signals, the multimodal stimulation subsystem is synchronously activated according to a preset paradigm, including: The motion parameters of the visual stimulus are dynamically adjusted within a preset range according to the program instructions, and the start and end times of the visual stimulus are controlled by the trigger output module in the synchronization control system so that the visual stimulus is synchronized with the exposure signal of the pupil recording camera; the motion parameters include the brightness, color and motion mode of the programmable visual screen. A directional sound source ranging from 20 Hz to 32 kHz is generated through a dual-channel speaker. The dual-channel delay is calibrated by a synchronous control system to ensure that the sound waves arrive at the ear canal simultaneously. Based on the event-triggered mode, visual stimuli are linked to generate a composite sensory input. Airflow stimulation is applied with an accuracy of ±0.5 mm using a beard stimulator, which is a miniature pneumatic nozzle. The nozzle angle of the miniature pneumatic nozzle is dynamically adjusted according to the mouse's head posture to maintain a constant position of the stimulation target. The channel mapping data of the multi-channel electrical stimulation electrode array is invoked, and an adjustable current is output in a space-time encoding mode.

[0049] Specifically, in some embodiments, the multimodal stimulation subsystem includes a programmable visual screen (e.g., 1920×1080 resolution, refresh rate ≥60Hz) located 10 cm opposite to the target brain region of the mouse and at eye level; a dual-channel speaker symmetrically positioned 10 cm from the mouse's ear; a whisker stimulator located 2 to 3 cm below the face; an adjustable licking device located 5 cm below and in front of the face; and a multi-channel electrical stimulation electrode array integrated into the mouse's head. Figure 2 As shown, the mouse multimodal stimulation and whole-brain recording platform includes: b. visual stimulation (device), such as a programmable visual screen; c. auditory stimulation (device), such as a dual-channel speaker; d. beard stimulation (device), such as a beard stimulator; e. licking water (device); and f. electrode stimulation and recording, such as a multichannel electrical stimulation electrode array.

[0050] This invention combines multiple basic stimulation paradigms and provides location settings for stimulation devices to ensure that mice receive appropriate stimulation during experiments.

[0051] Step 103, applying multimodal stimulation, can be achieved through the following steps: (1) Applying visual stimuli: The motion parameters of the visual stimulus are dynamically adjusted within a preset range according to the program instructions, and the start and end times of the visual stimulus are controlled by the trigger output module in the synchronization control system so as to synchronize the visual stimulus with the exposure signal of the pupil recording camera.

[0052] The motion parameters include the brightness, color, and motion mode of the programmable visual screen, such as the flicker frequency and pattern mode.

[0053] (2) Apply auditory stimulation: A directional sound source ranging from 20 Hz to 32 kHz is generated through a dual-channel speaker. The dual-channel delay is calibrated by a synchronous control system to ensure that the sound waves arrive at the ear canal simultaneously. Based on an event-triggered mode, visual stimuli are linked to generate a composite sensory input.

[0054] (3) Apply beard stimulation: Airflow stimulation was applied with an accuracy of ±0.5 mm using a miniature pneumatic nozzle, which was then dynamically adjusted according to the mouse's head posture to maintain a constant target position.

[0055] For example, the beard stimulation module uses a micro-pneumatic nozzle or a microrod array driven by a piezoelectric motor, positioned 2–3 cm below the sides of the mouse's face, to simulate airflow, touch, or vibration stimulation with an accuracy of ±0.5 mm. (4) Applying electrical stimulation: The channel mapping data of the multi-channel electrical stimulation electrode array is invoked, and an adjustable current is output in a space-time encoding mode.

[0056] For example, an electrical stimulation system consists of an electrode array implanted in the cortex or body of a mouse connected to a current source controller (output range 0.1–10V, frequency 1–500Hz), which performs parametric adjustment and targeted stimulation under programmed control.

[0057] To achieve high-precision device synchronization and signal management, this invention introduces an integrated synchronization control system. This system is based on NI or DAQ multifunction I / O boards and controlled by custom programs (such as Python scripts or LabVIEW interfaces). Each stimulation device outputs TTL or analog signals during activation; these signals are acquired in real-time by the I / O devices and aligned with the sampling clock output by the recording devices (such as calcium imaging systems or electrode recording systems).

[0058] The method provided in this embodiment combines a multimodal stimulation paradigm and provides a location setting for the stimulation device to ensure that mice receive appropriate stimulation during the experiment.

[0059] According to the present invention, a method for multimodal stimulation and whole-brain recording of mice is provided. The multimodal recording subsystem includes a scanning light field calcium imaging device vertically aligned with the mouse head, a pupil recording camera located 10-15 cm above a programmable visual screen, and a running speed sensor at the bottom of the platform. Neural activity data of mice were collected using a multimodal recording subsystem, including: The calcium signal was obtained by tracking the head movement of mice in real time using a scanning light field calcium imaging device; the scanning light field calcium imaging device integrates wide field imaging technology and dynamic focusing module. Eye tracking is assisted by a near-infrared light source in a pupil recording camera to obtain pupil change signals. These signals are then correlated with visual stimulus timestamps to calculate visual response delay. The pupil change signals represent pupil diameter change data. The running speed of the mice was collected using a running speed sensor; Real-time acquisition of feedback electrode signals from a multi-channel electrical stimulation electrode array.

[0060] Specifically, in some embodiments, the multimodal recording subsystem includes a scanning light field calcium imaging device vertically aligned with the mouse's head, a pupil recording camera positioned 10-15 cm above a programmable visual screen, and a running speed sensor at the bottom of the platform. For example... Figure 2 As shown, the mouse multimodal stimulation and whole-brain recording platform includes a. a whole-brain calcium imaging device, h. a treadmill and a pupil recording camera.

[0061] Step 104 can be achieved through the following steps: First, calcium signals were obtained by tracking mouse head movements in real time using a scanning light field calcium imaging device. This device integrates wide-field imaging technology and a dynamic focusing module. The scanning light field technology can automatically adjust the focal length and track the focus based on the mouse's activity.

[0062] For example, scanning light field calcium imaging devices (such as whole-brain calcium signal recording devices) use highly sensitive light sensors and are equipped with dedicated data analysis software for signal decoding and analysis.

[0063] Furthermore, eye tracking is assisted by a near-infrared light source in a pupil recording camera to obtain pupil change signals, and these signals are correlated with visual stimulus timestamps to calculate visual response delay; the pupil change signals represent pupil diameter change data.

[0064] The pupil recording device uses a high-resolution camera and features autofocus, tracking, and image analysis capabilities. Furthermore, the running speed of the mice was collected using a running speed sensor.

[0065] Velocity sensors are devices used to measure the speed of moving objects. They come in various principles and types, and are suitable for different scenarios. The core measurement principles include direct velocity measurement (calculating velocity by measuring displacement per unit time) and indirect velocity measurement (converting other physical quantities into velocity based on physical laws). The specific sensor type (such as contact sensor or non-contact sensor) can be determined according to actual measurement needs.

[0066] Furthermore, the feedback electrode signals from the multi-channel electrical stimulation electrode array are acquired in real time.

[0067] The method provided in this embodiment utilizes a platform capable of visual, auditory, beard, water-licking, and electrical stimulation, meeting diverse experimental needs. Multimodal recording techniques include whole-brain calcium imaging RUSH, electrode recording, pupillary recording, and treadmill recording. This invention provides, for the first time, a platform and method capable of isolating external noise and recording whole-brain multimodal neural activity under various stimulation conditions.

[0068] According to the present invention, a method for multimodal stimulation and whole-brain recording in mice includes a synchronous control system comprising a multifunctional I / O device, a trigger output module, and a signal processing program. The synchronous control system receives all stimulus trigger signals and neural activity data of the mouse, aligns the temporal sequence of all stimulus trigger signals and neural activity data of the mouse, marks them with a unified timestamp, and writes the timestamp-aligned stimulus parameters and neural activity data into an NWB or HDF5 standardized container via the multifunctional I / O device. The method includes: A multi-functional I / O device was used to receive calcium signals, pupillary change signals, running speed, and electrode signals from mice. The trigger output module uses a ring buffer mechanism to align the timing of stimulation parameters with calcium signals, pupil change signals, running speed, and electrode signals according to the sampling clocks of all devices, and marks them with a unified timestamp. The time-stamped stimulation parameters, along with calcium signals, pupillary change signals, running speed, and electrode signals, are written into an NWB or HDF5 normalized container using a signal processing program.

[0069] Specifically, in some embodiments, the synchronization control system includes a multi-functional I / O device, a trigger output module, and a signal processing program.

[0070] Step 105 can be achieved through the following steps: First, a multi-functional I / O device is used to receive the calcium signal, pupillary change signal, running speed, and electrode signal of the mouse. Then, the trigger output module is used to align the timing of the stimulation parameters with the calcium signal, pupillary change signal, running speed, and electrode signal according to the sampling clock of all devices through a ring buffer mechanism, and mark them with a uniform timestamp. Further, the timestamp-aligned stimulation parameters with the calcium signal, pupillary change signal, running speed, and electrode signal are written into an NWB or HDF5 standardized container through a signal processing program.

[0071] In order to ensure that all recording and stimulation devices can be accurately synchronized, the method provided in this embodiment introduces a synchronization control system, including a multi-functional IO device, a trigger output module, and a signal processing program. This invention provides a novel mouse multimodal stimulation and whole-brain recording platform and method, providing a more powerful and flexible tool for neuroscience research.

[0072] A method for multimodal stimulation and whole-brain recording in mice according to the present invention further includes: When a dropped frame in the imaging corresponding to a calcium signal is detected, the stimulation sequence is automatically paused and data re-acquisition is triggered. The motion parameters of the visual stimulus are adjusted in real time based on running speed.

[0073] Specifically, in some embodiments, the closed-loop synchronization control further includes: When a dropped frame is detected in calcium imaging, the stimulation sequence is automatically paused and data re-acquisition is triggered; then, the motion parameters of the visual stimulus are adjusted in real time based on the running speed.

[0074] The closed-loop synchronization mechanism in this embodiment ensures the reliability and consistency of data acquisition.

[0075] A method for multimodal stimulation and whole-brain recording in mice according to the present invention further includes: Stimulation parameters, device response logs, and raw neural signals are associated and stored in a standardized NWB or HDF5 container. Metadata indexes that generate reproducible experimental procedures based on stimulus parameters, device response logs, and raw neural signals.

[0076] Specifically, in some embodiments, the method further includes a data integration step, which includes the following: Stimulation parameters, device response logs, and raw neural signals are stored together in a standardized NWB or HDF5 container. Then, a metadata index for reproducible experimental procedures is generated based on the stimulation parameters, device response logs, and raw neural signals.

[0077] The method provided in this embodiment generates a metadata index by using stimulation parameters, device response logs, and raw neural signals, which facilitates the reproducibility of the experimental process and makes the invention highly reusable.

[0078] In some embodiments, the control program includes the following functional modules: Signal buffer and time alignment module: Uses a ring buffer mechanism to record the timing information of all input channels and uniformly calibrates them through a clock source; Event Trigger Management: Supports trigger control based on preset sequences or random events, such as the synchronous presentation of auditory and visual stimuli; Signal processing and analysis module: performs real-time filtering of the acquired signals, detects anomalies (such as exceeding limits or trigger failures), and automatically generates logs; Data synchronization writing module: Writes the timestamps of stimuli and records along with the master experimental data into a standard data format (such as HDF5 or NWB) for easy subsequent analysis.

[0079] The system also supports extended online control functions, allowing users to manually adjust parameters such as trigger delay, pulse width, and signal channel allocation through a GUI interface to adapt to the needs of different experimental paradigms.

[0080] To comprehensively record the neural activity of mice, we employed the whole-brain calcium imaging RUSH technique, an advanced calcium imaging technology. In addition, we also used scanning light field technology and wide-field imaging technology.

[0081] To improve the accuracy and reliability of signal monitoring, this invention improves the detection method, mainly in three aspects: event alignment mechanism, feedback confirmation process, and data structure integration. Traditional trigger signals are only used to send control pulses and cannot determine whether each module is actually responding. This invention, however, constructs a trigger-feedback closed-loop mechanism to receive signals from the target device in real time after stimulation (such as camera exposure TTL and electrical stimulation output confirmation signals), and the control program automatically determines the validity of the signal, achieving real-time confirmation and fault-tolerant detection of the event. Simultaneously, this invention employs a unified timestamp labeling mechanism, combined with high-precision I / O devices and a buffer loop recording strategy, to uniformly synchronize stimulus outputs and recording samples from multiple channels to a single time base, achieving millisecond-level event alignment accuracy. Furthermore, this invention writes all monitoring data and neural activity data together into a standardized data container (such as NWB format) and includes an automatically generated event log, greatly improving the traceability and reproducibility of data analysis. These improvements not only enhance the accuracy of signal synchronization but also significantly strengthen the experimental system's control capability and robustness for multimodal complex tasks.

[0082] All of these devices are synchronized with a multi-functional I / O device to ensure that all data is accurately recorded during the experiment.

[0083] In summary, this invention provides a novel and efficient method for recording neural activity in mice, which can not only provide mice with a variety of stimuli, but also accurately record their neural activity in an environment isolated from external interference.

[0084] The mouse multimodal stimulation and whole-brain recording device provided by the present invention will be described below. The mouse multimodal stimulation and whole-brain recording device described below and the mouse multimodal stimulation and whole-brain recording method described above can be referred to in correspondence.

[0085] Figure 4 This is a schematic diagram of the structure of the mouse multimodal stimulation and whole-brain recording device provided by the present invention. The mouse multimodal stimulation and whole-brain recording device 400 is applied to a mouse multimodal stimulation and whole-brain recording platform, which includes a soundproof shell system, a modular support system, a multimodal stimulation subsystem, a multimodal recording subsystem, and a synchronization control system. Figure 4 As shown, the mouse multimodal stimulation and whole-brain recording device 400 includes an initialization and startup module 410, a receiving module 420, a multimodal stimulation application module 430, a recording module 440, and a signal synchronization control module 450. The initialization and startup module 410 is used to fix the mouse in the center of the mouse multimodal stimulation and whole brain recording platform, adjust the modular support system so that each device meets the preset spatial position relationship, close the soundproof shell system, and activate the sealing ring to isolate external noise. The receiving module 420 is used to receive all stimulus trigger signals and record the sampling clocks of all devices through the multi-functional IO device in the synchronization control system; The multimodal stimulation application module 430 is used to synchronously activate the multimodal stimulation subsystem according to a preset paradigm in response to all the stimulation trigger signals; the multimodal stimulation subsystem is used to simultaneously apply visual stimulation, auditory stimulation, whisker stimulation, licking device stimulation and electrical stimulation to the mouse. The recording module 440 is used to collect neural activity data of the mouse through the multimodal recording subsystem; the neural activity data includes calcium signals, pupillary change signals, running speed, and electrode signals; The signal synchronization control module 450 is used to receive all the stimulus trigger signals and the neural activity data of the mouse through the synchronization control system, align the timing of all the stimulus trigger signals and the neural activity data of the mouse and mark them with a unified timestamp, and write the timestamp-aligned stimulus parameters and the neural activity data into an NWB or HDF5 standardized container through the multi-functional IO device.

[0086] The device provided in this embodiment is applied to a mouse multimodal stimulation and whole-brain recording platform. The mouse multimodal stimulation and whole-brain recording platform includes a soundproof shell system, a modular support system, a multimodal stimulation subsystem, a multimodal recording subsystem, and a synchronization control system. First, the initialization and startup module 410 is used to fix the mouse in the center of the mouse multimodal stimulation and whole-brain recording platform, adjust the modular support system to ensure that each device meets the preset spatial position relationship, close the soundproof shell system, and activate the sealing ring to isolate external noise. The receiving module 420 is used to receive all stimulation trigger signals and record the sampling clocks of all devices through the multi-functional I / O device in the synchronization control system. Then, the multimodal stimulation application module 430 is used to respond to all stimulation trigger signals. The multimodal stimulation subsystem is synchronously activated according to a preset paradigm. The multimodal stimulation subsystem is used to simultaneously apply visual stimulation, auditory stimulation, whisker stimulation, water-licking device stimulation, and electrical stimulation to the mouse. Further, the recording module 440 is used to collect the mouse's neural activity data through the multimodal recording subsystem. The neural activity data includes calcium signals, pupillary change signals, running speed, and electrode signals. Then, the signal synchronization control module 450 is used to receive all stimulation trigger signals and the mouse's neural activity data through the synchronization control system, align the timing of all stimulation trigger signals and the mouse's neural activity data and mark them with a unified timestamp, and write the timestamp-aligned stimulation parameters and neural activity data into an NWB or HDF5 standardized container through a multifunctional IO device.

[0087] This invention provides an efficient platform and method that can provide multimodal stimulation and record multimodal neural activity of the whole brain, which helps to understand brain function more deeply and also provides a more complete technical means for neuroscience research.

[0088] According to the present invention, a mouse multimodal stimulation and whole brain recording device 400 is provided. The multimodal stimulation subsystem includes a programmable visual screen located 10 cm to the side of the target brain region of the mouse and at the level of both eyes, a dual-channel speaker symmetrically arranged 10 cm from the mouse's ear, a beard stimulator located 2 to 3 cm below the face, an adjustable licking device located 5 cm in front and below, and a multi-channel electrical stimulation electrode array integrated into the mouse's head. The multimodal stimulus application module 430 is specifically used for: The motion parameters of the visual stimulus are dynamically adjusted within a preset range according to the program instructions, and the start and end times of the visual stimulus are controlled by the trigger output module in the synchronization control system so that the visual stimulus is synchronized with the exposure signal of the pupil recording camera; the motion parameters include the brightness, color and motion mode of the programmable visual screen; The dual-channel audio system generates a directional sound source of 20 Hz to 32 kHz, and the dual-channel delay is calibrated by the synchronous control system to ensure that the sound waves arrive at the ear canal simultaneously. Based on the event triggering mode, the visual stimulus is linked to generate a composite sensory input. Airflow stimulation is applied with an accuracy of ±0.5 mm using the beard stimulator, which is a miniature pneumatic nozzle; the nozzle angle of the miniature pneumatic nozzle is dynamically adjusted according to the mouse's head posture to maintain a constant stimulation target position. The channel mapping data of the multi-channel electrostimulation electrode array is invoked, and an adjustable current is output in a space-time encoding mode.

[0089] According to the present invention, a mouse multimodal stimulation and whole brain recording device 400 is provided, wherein the multimodal recording subsystem includes a scanning light field calcium imaging device vertically aligned with the mouse head, a pupil recording camera located 10-15 cm above a programmable visual screen, and a running speed sensor at the bottom of the platform. The recording module 440 is specifically used for: The calcium signal is obtained by tracking the mouse head movement in real time using the scanning light field calcium imaging device; the scanning light field calcium imaging device integrates wide field imaging technology and dynamic focusing module; The pupil change signal is obtained by using a near-infrared light source in the pupil recording camera to assist eye tracking, and the pupil change signal is correlated with the visual stimulus timestamp to calculate the visual response delay; the pupil change signal represents pupil diameter change data. The running speed of the mouse was collected using a running speed sensor; The electrode signals fed back from the multi-channel electrical stimulation electrode array are acquired in real time.

[0090] According to the present invention, a mouse multimodal stimulation and whole-brain recording device 400 is provided, wherein the synchronous control system includes a multifunctional I / O device, a trigger output module and a signal processing program; The signal synchronization control module 450 is specifically used for: The multi-functional I / O device is used to receive the calcium signal, pupil change signal, running speed, and electrode signal of the mouse. The trigger output module uses a ring buffer mechanism to align the timing of the stimulation parameters with the calcium signal, the pupil change signal, the running speed, and the electrode signal according to the sampling clock of all devices, and marks them with a unified timestamp. The time-stamp-aligned stimulation parameters, along with the calcium signal, pupillary change signal, running speed, and electrode signal, are written into the NWB or HDF5 normalized container using the signal processing program.

[0091] According to the mouse multimodal stimulation and whole-brain recording device 400 provided by the present invention, the signal synchronization control module 450 is further used for: When the imaging frame drop corresponding to the calcium signal is detected, the stimulation sequence is automatically paused and data re-acquisition is triggered. The motion parameters of the visual stimulus are adjusted in real time based on the running speed.

[0092] According to the mouse multimodal stimulation and whole-brain recording device 400 provided by the present invention, the signal synchronization control module 450 is further used for: The stimulation parameters, device response logs, and raw neural signals are stored in the NWB or HDF5 standardized container. Based on the stimulation parameters, the device response logs, and the original neural signals, a metadata index is generated that allows for the reproducibility of the experimental procedure.

[0093] Figure 5 An example is a schematic diagram of the physical structure of an electronic device, such as... Figure 5 As shown, the electronic device may include: a processor 510, a communication interface 520, a memory 530, and a communication bus 540, wherein the processor 510, the communication interface 520, and the memory 530 communicate with each other through the communication bus 540. The processor 510 can call logical instructions in the memory 530 to execute a mouse multimodal stimulation and whole-brain recording method. This method is applied to the mouse multimodal stimulation and whole-brain recording platform, which includes a soundproof shell system, a modular scaffold system, a multimodal stimulation subsystem, a multimodal recording subsystem, and a synchronization control system. The method includes: The mouse is fixed in the center of the mouse multimodal stimulation and whole brain recording platform. The modular support system is adjusted so that each device meets the preset spatial position relationship. The soundproof shell system is closed and the sealing ring is activated to isolate external noise. The multi-functional I / O device in the synchronous control system receives all stimulus trigger signals and records the sampling clocks of all devices. In response to all the stimulus trigger signals, the multimodal stimulation subsystem is synchronously activated according to a preset paradigm; the multimodal stimulation subsystem is used to simultaneously apply visual stimulation, auditory stimulation, whisker stimulation, licking device stimulation and electrical stimulation to the mouse; The neural activity data of the mouse was acquired using the multimodal recording subsystem; the neural activity data included calcium signals, pupillary change signals, running speed, and electrode signals. The synchronous control system receives all stimulus trigger signals and the neural activity data of the mouse, aligns the timing of all stimulus trigger signals and the neural activity data of the mouse and marks them with a unified timestamp, and writes the timestamp-aligned stimulus parameters and the neural activity data into an NWB or HDF5 standardized container through the multi-functional IO device.

[0094] Furthermore, the logical instructions in the aforementioned memory 530 can be implemented as software functional units and, when sold or used as independent products, can be stored in a computer-readable storage medium. Based on this understanding, the technical solution of the present invention, or the part that contributes to the prior art, or a part of the technical solution, can be embodied in the form of a software product. This computer software product is stored in a storage medium and includes several instructions to cause a computer device (which may be a personal computer, server, or network device, etc.) to execute all or part of the steps of the methods described in the various embodiments of the present invention. The aforementioned storage medium includes various media capable of storing program code, such as USB flash drives, portable hard drives, read-only memory (ROM), random access memory (RAM), magnetic disks, or optical disks.

[0095] On the other hand, the present invention also provides a computer program product, the computer program product comprising a computer program, which can be stored on a non-transitory computer-readable storage medium. When the computer program is executed by a processor, the computer is able to execute the mouse multimodal stimulation and whole-brain recording method provided by the above methods. This method is applied to the mouse multimodal stimulation and whole-brain recording platform, the mouse multimodal stimulation and whole-brain recording platform comprising a soundproof shell system, a modular scaffold system, a multimodal stimulation subsystem, a multimodal recording subsystem, and a synchronization control system; the method includes: The mouse is fixed in the center of the mouse multimodal stimulation and whole brain recording platform. The modular support system is adjusted so that each device meets the preset spatial position relationship. The soundproof shell system is closed and the sealing ring is activated to isolate external noise. The multi-functional I / O device in the synchronous control system receives all stimulus trigger signals and records the sampling clocks of all devices. In response to all the stimulus trigger signals, the multimodal stimulation subsystem is synchronously activated according to a preset paradigm; the multimodal stimulation subsystem is used to simultaneously apply visual stimulation, auditory stimulation, whisker stimulation, licking device stimulation and electrical stimulation to the mouse; The neural activity data of the mouse was acquired using the multimodal recording subsystem; the neural activity data included calcium signals, pupillary change signals, running speed, and electrode signals. The synchronous control system receives all stimulus trigger signals and the neural activity data of the mouse, aligns the timing of all stimulus trigger signals and the neural activity data of the mouse and marks them with a unified timestamp, and writes the timestamp-aligned stimulus parameters and the neural activity data into an NWB or HDF5 standardized container through the multi-functional IO device.

[0096] In another aspect, the present invention also provides a non-transitory computer-readable storage medium storing a computer program thereon, which, when executed by a processor, implements the mouse multimodal stimulation and whole-brain recording method provided by the methods described above. This method is applied to the mouse multimodal stimulation and whole-brain recording platform, which includes a soundproof shell system, a modular scaffold system, a multimodal stimulation subsystem, a multimodal recording subsystem, and a synchronization control system; the method includes: The mouse is fixed in the center of the mouse multimodal stimulation and whole brain recording platform. The modular support system is adjusted so that each device meets the preset spatial position relationship. The soundproof shell system is closed and the sealing ring is activated to isolate external noise. The multi-functional I / O device in the synchronous control system receives all stimulus trigger signals and records the sampling clocks of all devices. In response to all the stimulus trigger signals, the multimodal stimulation subsystem is synchronously activated according to a preset paradigm; the multimodal stimulation subsystem is used to simultaneously apply visual stimulation, auditory stimulation, whisker stimulation, licking device stimulation and electrical stimulation to the mouse; The neural activity data of the mouse was acquired using the multimodal recording subsystem; the neural activity data included calcium signals, pupillary change signals, running speed, and electrode signals. The synchronous control system receives all stimulus trigger signals and the neural activity data of the mouse, aligns the timing of all stimulus trigger signals and the neural activity data of the mouse and marks them with a unified timestamp, and writes the timestamp-aligned stimulus parameters and the neural activity data into an NWB or HDF5 standardized container through the multi-functional IO device.

[0097] The device embodiments described above are merely illustrative. The units described as separate components may or may not be physically separate. The components shown as units may or may not be physical units; that is, they may be located in one place or distributed across multiple network units. Some or all of the modules can be selected to achieve the purpose of this embodiment according to actual needs. Those skilled in the art can understand and implement this without any creative effort.

[0098] Through the above description of the embodiments, those skilled in the art can clearly understand that each embodiment can be implemented by means of software plus necessary general-purpose hardware platforms, and of course, it can also be implemented by hardware. Based on this understanding, the above technical solutions, in essence or the part that contributes to the prior art, can be embodied in the form of a software product. This computer software product can be stored in a computer-readable storage medium, such as ROM / RAM, magnetic disk, optical disk, etc., and includes several instructions to cause a computer device (which may be a personal computer, server, or network device, etc.) to execute the methods described in the various embodiments or some parts of the embodiments.

[0099] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, and not to limit them; although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that modifications can still be made to the technical solutions described in the foregoing embodiments, or equivalent substitutions can be made to some of the technical features; and these modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the spirit and scope of the technical solutions of the embodiments of the present invention.

Claims

1. A method of mouse multimodal stimulation and whole-brain recording, comprising: The application is applied to a mouse multi-modal stimulation and whole brain recording platform, which comprises a soundproof housing system, a modular support system, a multi-modal stimulation subsystem, a multi-modal recording subsystem and a synchronous control system; the method comprises: Fixing the mouse in the center of the mouse multi-modal stimulation and whole brain recording platform, adjusting the modular support system to make each device meet the preset spatial positional relationship, closing the soundproof housing system, and activating the sealing ring to isolate external noise; Receiving all stimulation trigger signals and recording the sampling clock of all devices through the multifunctional IO device in the synchronous control system; Synchronously starting the multi-modal stimulation subsystem according to the preset paradigm in response to the all stimulation trigger signals; the multi-modal stimulation subsystem is used for simultaneously applying visual stimulation, auditory stimulation, whisker stimulation, water licking device stimulation and electrical stimulation to the mouse; Collecting the neural activity data of the mouse through the multi-modal recording subsystem; the neural activity data comprises calcium signals, pupil change signals, running speed and electrode signals; Receiving the all stimulation trigger signals and the neural activity data of the mouse through the synchronous control system, aligning the time sequence of the all stimulation trigger signals and the neural activity data of the mouse and marking a unified time stamp, and writing the stimulation parameters and the neural activity data aligned in time into a NWB or HDF5 standardized container through the multifunctional IO device.

2. The mouse multimodal stimulation and whole-brain recording method of claim 1, wherein, The multi-modal stimulation subsystem comprises a programmable visual screen located 10 cm away from the target brain region of the mouse and at the horizontal height of the two eyes, a double-channel sound system symmetrically arranged 10 cm away from the ears of the mouse, a whisker stimulator located 2-3 cm below the face, an adjustable water licking device 5 cm in front and below, and a multi-channel electrical stimulation electrode array integrated in the head of the mouse; The response to the all stimulation trigger signals and the synchronous starting of the multi-modal stimulation subsystem according to the preset paradigm comprises: Dynamically adjusting the motion parameters of the visual stimulation in the preset range according to the program instructions, and controlling the starting time and the ending time of the visual stimulation by the trigger output module in the synchronous control system, so that the visual stimulation is synchronized with the pupil recording camera exposure signal; the motion parameters comprise the brightness, color and motion mode of the programmable visual screen; Generating a directional sound source of 20 Hz to 32 kHz through the double-channel sound system, calibrating the double-channel delay by the synchronous control system to ensure that the sound waves reach the ear canal at the same time, and generating a composite sensory input based on the event trigger mode linkage of the visual stimulation; Applying air flow stimulation with ±0.5 mm precision through the whisker stimulator, which is a micro pneumatic nozzle; dynamically adjusting the nozzle angle of the micro pneumatic nozzle according to the head posture of the mouse to maintain the constant position of the stimulation target point; Calling the channel mapping data of the multi-channel electrical stimulation electrode array, and outputting adjustable current according to the spatial and temporal coding mode.

3. The mouse multimodal stimulation and whole-brain recording method of claim 1, wherein, The multi-modal recording subsystem includes a scanning light field calcium imaging device vertically aligned with the mouse head, a pupil recording camera 10-15 cm above the programmable visual screen, and a running speed sensor at the bottom of the platform; The method further comprises: The method further comprises: The calcium signal is obtained by tracking the mouse head movement in real time through the scanning light field calcium imaging device; the scanning light field calcium imaging device integrates wide-field imaging technology and a dynamic focusing module; The pupil change signal is obtained by assisting eye tracking through the near-infrared light source in the pupil recording camera, and the pupil change signal is associated with the visual stimulation time stamp to calculate the visual response delay; the pupil change signal represents the pupil diameter change data; The running speed of the mouse is collected through the running speed sensor; 4. The mouse multimodal stimulation and whole-brain recording method of claim 1, wherein, The electrode signal of the multi-channel electrical stimulation electrode array is collected in real time. The synchronization control system includes a multi-functional IO device, a trigger output module, and a signal processing program; the synchronization control system receives all the stimulation trigger signals and the neural activity data of the mouse, aligns the timing of all the stimulation trigger signals and the neural activity data of the mouse, and labels a unified time stamp, and writes the time-stamped stimulation parameters and the neural activity data into the NWB or HDF5 standardized container through the multi-functional IO device, including: The calcium signal, the pupil change signal, the running speed of the mouse, and the electrode signal of the mouse are collected through the multi-functional IO device; The timing of the stimulation parameters and the calcium signal, the pupil change signal, the running speed, and the electrode signal is aligned according to the sampling clock of all devices through the ring buffer mechanism of the trigger output module, and a unified time stamp is labeled; 5. The method of claim 1, wherein, The time-stamped stimulation parameters and the calcium signal, the pupil change signal, the running speed, and the electrode signal are written into the NWB or HDF5 standardized container through the signal processing program. The method further comprises: When the imaging frame drop corresponding to the calcium signal is detected, the stimulation sequence is automatically paused and data re-collection is triggered; 6. The method of claim 1, wherein, The motion parameters of the visual stimulation are adjusted in real time based on the running speed. The method further comprises: The stimulation parameters, device response logs, and raw neural signals are stored in the NWB or HDF5 standardized container; 7. A mouse multimodal stimulation and whole-brain recording device, comprising: The metadata index of the reproducible experimental process is generated based on the stimulation parameters, the device response logs, and the raw neural signals. The mouse multi-modal stimulation and whole brain recording platform includes a soundproof enclosure system, a modular support system, a multi-modal stimulation subsystem, a multi-modal recording subsystem, and a synchronization control system; the device includes: An initialization and start module is used to fix the mouse in the center of the mouse multi-modal stimulation and whole brain recording platform, adjust the modular support system to make each device meet the preset spatial positional relationship, close the soundproof enclosure system, and activate the sealing ring to isolate external noise; a receiving module configured to receive all stimulation trigger signals and record sampling clocks of all devices through a multifunctional IO device in the synchronization control system; a multi-modal stimulation applying module configured to synchronously start the multi-modal stimulation subsystem according to a preset paradigm in response to the all stimulation trigger signals; the multi-modal stimulation subsystem is configured to simultaneously apply visual stimulation, auditory stimulation, whisker stimulation, water licking device stimulation, and electrical stimulation to the mouse; a recording module configured to collect neural activity data of the mouse through the multi-modal recording subsystem; the neural activity data includes calcium signals, pupil change signals, running speed, and electrode signals; a signal synchronization control module configured to receive the all stimulation trigger signals and the neural activity data of the mouse through the synchronization control system, align the all stimulation trigger signals and the neural activity data of the mouse in time sequence, mark a unified timestamp, and write the stimulation parameters and the neural activity data after timestamp alignment into a NWB or HDF5 standardized container through the multifunctional IO device.

8. An electronic device comprising a memory, a processor, and a computer program stored on the memory and executable on the processor, characterized in that, The processor executes the computer program to implement the mouse multi-modal stimulation and whole brain recording method according to any one of claims 1 to 6. 9.A non-transitory computer-readable storage medium having stored thereon a computer program, characterized in that, The computer program is executed by the processor to implement the mouse multi-modal stimulation and whole brain recording method according to any one of claims 1 to 6.

10. A computer program product comprising a computer program, characterized in that, The computer program is executed by the processor to implement the mouse multi-modal stimulation and whole brain recording method according to any one of claims 1 to 6.

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