Neurobehavioral evaluation method for animal models of vascular cognitive impairment-Work memory evaluation method
Neurobehavioral evaluation method for animal models of vascular cognitive impairment- Work memory evaluation method
Since its first introduction in vascular cognitive impairment (VCI) in 1993, it has become the focus of social attention in the past 20 years, and is also a hot topic in the field of neuroscience. The incidence of VCI is increasing year by year, and its incidence is second only to Alzheimer disease (AD). It is one of the important factors that cause dementia in old age and lead to the decline of quality of life in the elderly. Although the clinical research of VCI has made some progress, the pathogenesis and pathophysiological changes of VCI are still unclear. Therefore, more basic research is urgently needed to provide a theoretical basis for the early diagnosis and treatment of VCI.
The biggest difference between clinical research and basic research is that clinical research can directly reflect the cognitive status of patients through various scales such as MMSE and Moca, and the identification of animal cognitive impairment can only be accomplished through various evaluation tools. However, the cognitive evaluation tools reported in the literature and their applications are various, so we analyzed the evaluation methods and their applications commonly used in recent literature, and summarized the common evaluation of the cognitive functions of experimental animals before export. , working memory, etc.
An executive function is a collaborative operation of many cognitive processes of an individual. It involves various operational processes that monitor and control individual consciousness and behavior, including self-regulation, cognitive flexibility, response inhibition, planning, and so on. Working memory (WM) is the most common method for evaluating the performance of experimental animals. Working memory refers to the process of temporary storage and processing of information during the execution of cognitive tasks. Working memory is achieved in humans and caries by relying on the prefrontal cortex. The common methods for evaluating working memory are as follows.
2. 1 autonomous alternating experiment T, Y maze autonomous (spontaneous alternation on a T / Y-maze) is used to evaluate the learning ability of experimental animals. Even without a food reward, the rat retains some novelty about the area being explored. The number of spontaneous conversions/total number of selections was used to illustrate the working memory function, and the VCI animal ratio score decreased. Normal alternating operations are consistent with full working memory capabilities. T-maze and Y-maze autonomous conversion experiments have been widely used in VCI studies. Moreover, selective working memory impairment occurred in the bilateral common carotid stenosis model and the bilateral common carotid artery occlusion model.
2. 2 MWM working memory refers to the experimental method of transforming the Morris water maze. By changing the position of the escape platform every day, the experimental animals are forced to find a new escape platform location network, also known as delayed matched sample task. Sample task DMST). Mainly through the 4d training, the training method is the same as the reference memory, but the position of the escape platform is changed every day, forcing the experimental animals to learn the location of the new escape platform every day. Working memory ability was observed by comparison of the escape latency during the first training session and the escape latency of the fourth test phase.
Some scholars also complete the measurement of working memory by training the pairing method twice a day. The main process is as follows: the experiment consists of 12 days, training twice a day, the first training every day is for information acquisition, the escape platform is placed at a different position from the previous 1d training; the second is the memory retention test, the escape platform is placed in Information acquisition training is in the same position. Each group is 3d, and the interval between trainings in each group is 30 s, 30 min, 2 h, 6 h.
Some scholars also measure the working memory of animals through the relative phase. The main process is as follows: After the exploration training is completed, the platform is placed in the opposite quadrant of the quadrant where the original platform is located, in the same way as the acquired training. The parametric exploration training was conducted on the second day of the last para training, and the method was similar to the above-mentioned exploration training. However, some scholars believe that the parametric training belongs to the reference memory, but it can increase the sensitivity of the reference memory. In addition, MWM can also perform different types of delayed non-sample matching tasks, discrimination learning, etc. [-a.
However, the measurement of working memory by MWM takes a long time. After the reference memory training, the stress will increase the experimental interference factor, so the application is less than the radial arm maze.
2. 3 Radial Arm Maze Experiment The experimental animal can effectively determine the location of the arm where the food is placed by using the information provided by the distal cues in the room. The experimental method is the same as the reference memory evaluation method, except that the calculation method is different. The working memory errors refer to the animal that has entered the arm that has already eaten the grain in the same training. The water maze is different, and the radial arm maze is suitable for repeated testing. Or long-term memory testing, and working memory and reference memory can be completed simultaneously. Bilateral common carotid artery stenosis caused cognitive impairment in rats with functional impairment after 30 d and 6 m, which was associated with damage to the subfrontal cortical nerve circuit, which is similar to clinical subcortical ischemic vascular dementia. In the test of the radial arm maze, 2VO rats developed working memory disorder 21 days after surgery, and there was no obvious progressive exacerbation within 6 m. After 30 days of bilateral common carotid artery stenosis, selective working memory impairment occurred in RAM and no abnormality in reference memory.
2. The main process of the Jinyuta task experiment is exactly the same as the ZT spatial memory evaluation process. The experimental parameter evaluation method is the same as the RAM evaluation method. This method has proven to be a reliable evaluation method in micro-emboli caused cognitive impairment. ZT and RAM have many similarities in the evaluation of working memory, regardless of the experimental principle, experimental process and evaluation method. The biggest advantage is mainly to test the spatial reference memory; compared with MWM, it is mainly because the test environment is more comfortable and less stimulated to the experimental animals, so it can more accurately reflect the true cognitive situation.
2. 5-hole plate experiment The hole plate experiment usually includes three stages of adaptation, training and testing. The experimenter can perform according to the experimental stage required for the selection of the experimental mouth. Since the common hole plate may have food odor interference, a modified hole board test mHB was developed, and the food was fixed in each hole as a bait, and several (3) holes were placed separately for taking out and eating. food. The main observation indicators are the number of selection errors, the number of ignores, and the number of repeated selections. The number of times an animal enters a food hole (choosing the wrong choice), or the number of times the food hole is not provided (ignoring the error) can be used to evaluate the reference memory; the animal repeatedly enters the hole providing the food (repeated selection) to evaluate the working memory; the initial hole Latency, number of holes, duration of stay on the board/test time, static time/total time anxiety and depression. Compared with the MWM test, there is no stress factor in the mBH animal feeding and testing environment to avoid the interference of confounding factors; instead of food deprivation than RAM, it provides food rewards that are highly tempting to the experimental animals, so that the animals can cooperate well with the experiment; mBH can simultaneously test the motion, cognition and behavioral parameters, which is convenient for controlling the cooperation between groups, and the experimental results are more reliable. Improved hole plate testing is less useful in VCI research. It may be because the experiment takes a long time, and the adaptation and training phases take 14 days to complete, which is not suitable for short-term experiments.
2. 6 object recognition The object recognition test (object recognition test ORT) is a learning memory test method established by using the principle that animals innately explore new objects. The method has the characteristics of letting experimental animals perform learning and memory tests under freely active conditions, and can more closely simulate human learning and memory behaviors. Short-term memory (15 min) and long-term memory (24 h) can be evaluated according to the test interval. The familiarity of the experimental animals to two identical objects in the environment, the condition of the rats in contact with the two objects is recorded. One of them is replaced by a new object, mainly to observe the exploration of new objects in rats. In the ORT, the time of exploring the familiar object (TF) and exploring new objects (TN) in the experimental period is recorded separately. The identification index of the new object during the experimental period ( Rec_ognition indices } RI) is defined as TN / (TF + TN) x 100%, discrimination index DI TN - TN / (TF + TN) x 100% = i7. This method can be said to be a simple The working memory test is completely different from the reference memory; and it can be compared with the primate working memory; it is completely dependent on the animal nature to test without the need for reinforcement, so it is widely used.
Although executive function plays an important role in human cognitive function, the research is very extensive, but little research is done in animal experiments, or functional defects are rarely discussed separately. The executive function is mainly dependent on the structural and functional integrity of the prefrontal cortex, but other brain regions (hippocampus, striatum, etc.) are also affected in the animal model of cerebrovascular disease, so the description between the prefrontal cortex and the executive function is described separately. Direct relationships are difficult.
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