The Effects Of Long-term Maternal Separation On Object And Social Recognition In Rats

Object recognition test relies on the natural tendency of rodent to explore a novel object more than a familiar one. In the laboratory, the typical measure of object recognition memory is the time difference by a subject animal spending on exploring a novel object over a previously presented, and thus now familiar one. Social recognition test is a special case of object recognition. In this case, the object is a social stimulus(testing partner). Rodents also tend to spend more time interacting with a novel social partner than with a familiar one. Researchers have used the novel object recognition test and social recognition test to study learning and memory deficits as well as the social functioning deficits caused by drugs or genetic mutants. The standard one-trial object recognition task is one of the novelty-preference paradigms. It consists of a sampling trial(usually 2-10 min duration), during which rats explore two identical objects in a familiar arena, followed by a delayed test trial, in which a novel object is presented together with one familiar object already explored during this sampling trial. In the social recognition test, a subject animal is exposed to a testing partner repeatedly at certain time interval(e.g., 1h). When exposed to the same testing partner for a second time shortly after a first exposure, but within 1h, a sharp drop in investigatory behavior will occur. This drop in behavior is absent when the subject is exposed to a different testing partner or which the inter-exposure time exceeds 1-2 h. This time related social investigation of conspecifics is considered to be an ethological model for short-term social memory. Several features of novel object recognition and social interaction paradigms contribute to their advantage in studying cognitive disruption in a variety of human neurological or psychiatric disorders. They are established on the basis of the instinct behavior, and thus the animals can show their behavior without any reinforcement training. So they are simple, convenient, efficient and cost-saving(does not require complex or expensive equipment), ethologically relevant(on the base of animals’ preference for novel stimuli). However, these two models were usually used individually to assess the disruptiveness in object recognition and social recognition respectively in the neurological or psychiatric disorders. So the selectivity of functional deficits in different disorders could not be reflected, since different neurological or psychiatric disorders may show the selectivity in the impairment of object recognition and social recognition. It is of great importance to combine an object recognition and a social recognition component into a single experiment task. Cognitive deficits in the learning and memory domain, as well as deficits in social functioning have been reported in patients with schizophrenia, neurodegenerative diseases and brain damage. It is thus important to gain full understanding of brain mechanisms underlying object recognition and social recognition, so we could develop better treatments to battle these brain disorders. The new paradigm may be used in the field of cognition research to assess cognitive deficits and the underlying neural mechanisms in a range of animal models and to identify novel targets for drug therapy.In this project, we conducted four experiments totally. Firstly, we attempted to replicate previous work on the one-trial object recognition task(Experiment1). Next, we developed a new paradigm that combined the object and social recognition in one single task to assess learning and memory and social interaction(Experiment 2). This paradigm consists of 4 phases(trials). In the 1st test session, a subject rat is allowed to freely explore two identical objects(O1 and O1) and a social partner(coded as “A”) for 10 min. In the 2nd test session(novel object recognition), one of the objects is replaced with a new one(O2), the rest(O1 and A) remained unchanged. In the 3rd test session(novel location recognition), the location of the first object(O1) was changed, while the rest stimuli remained(O2 and A) the same. In the final test session(social recognition), the partner is replaced with a new one(B). The amount of time spent on exploring each object is recorded. To validate this new paradigm, we tested the cognitive and social disruptive effect of MK-801, a non-competitive NMDA receptor antagonist in this task(Experiment 3). Lastly, we assessed the long-term impacts of repeated maternal separation(6h/daily from postnatal days 2 to 21) on the object and social recognition(Experiment 4).Results from Experiment 1 showed that:(1) there was no difference in the exploration time of rats to two identical objects;(2) rats reduced the exploration time for familiar objects;(3) rats spent more time to explore new objects compared to the familiar one. Results from Experiments 2 show that:(1) rats spent more time interacting with the testing partner than with the two objects;(2) rats spent more time exploring new objects than familiar ones;(3) rats spent more time exploring the familiar object when its location was changed;(4) rats spent more time interacting with a new testing social partner than with a familiar one;(5) male rats spent more time exploring the objects and partner than female;(6) there was difference in the object exploration time and social interaction. Results from Experiment 3 revealed that:(1) Mk-801 at 0.1 mg/kg disrupted the object and social recognition;(2) the impairment of the object and social recognition was not due to the motor stimulating effect of MK-801;(3) there was a difference in the MK-801’s disruption of the object and social recognition. Results from Experiment 4 showed that early maternal separation changed the object recognition and social recognition in a dependent way. In conclusions, this project introduces a novel paradigm that combines an object recognition component with a social recognition component. It is valid in assessing object and social recognition deficits induced by MK-801 and in revealing the long-term detrimental impact of repeated maternal separation on cognition. Future work will be directed to reveal the neurobiology of object and social recognition.