DOPAMINE D-1 RECEPTOR MECHANISMS IN THE COGNITIVE PERFORMANCE OF YOUNG-ADULT AND AGED MONKEYS

Dopamine (DA) D-1 receptor compounds were examined in monkeys for effects on the working memory functions of the prefrontal cortex and on the fine motor abilities of the primary motor cortex. The D-1 antagonist, SCH23390, the partial D-1 agonist, SKF38393, and the full D-1 agonist, dihydrexidine, were characterized in young control monkeys, and in aged monkeys with naturally occurring catecholamine depletion. In addition, SKF38393 was tested in young monkeys experimentally depleted of catecholamines with chronic reserpine treatment. Injections of SCH23390 significantly impaired the memory performance of young control monkeys, but did not impair aged monkeys with presumed catecholamine depletion. Conversely, the partial agonist, SKF38393, improved the depleted monkeys (aged or reserpine-treated) but did not improve young control animals. The full agonist, dihydrexidine, did improve memory performance in young control monkeys, as well as in a subset of aged monkeys. Consistent with D, receptor mechanisms, agonist-induced improvements were blocked by SCH23390. Drug effects on memory performance occurred independently of effects on fine motor performance. These results underscore the importance of DA D-1 mechanisms in cognitive function, and provide functional evidence of DA system degeneration in aged monkeys. Finally, high doses of D-1 agonists impaired memory performance in aged monkeys, suggesting that excessive D-1 stimulation may be deleterious to cognitive function.

5-9岁儿童对常见食物及其功能的认知发展

Research on naïve biology investigates children spontaneous understanding of biology objects, phenomena and function. Previous researches focus mostly on biology phenomena. Little has done on organism’s function, such as eating food. Many research in this field found that children were unable to categorize food by nutrition criterion, but rely on physical cues. In order to investigate the development of children’s naïve understanding of food and to find if they can classify food by nutrition criterion, three age groups (5-year-olds, 7-year-olds, and 9-year-olds) were included in this study. Varies experimental tasks were also used to explore the children’s understanding of food and its function. The results showed as the followings: 1) A few 5-year- old children can classify food by nutrition criterion when they take the spontaneous classification task. However, more and more children can realize what make a kind of food different from another can be the nutrition it contains. 2) Kindergarteners can find the relation between food and its output. When they become older, more and more children can explain the relation by consistent theory. It can be said that 9-year-old children have already have a profound understanding of nutrition. They gradually developed naive theory of biology on nutrition level. 3) Even kindergarteners can understand the concept of “food balance”. However, with development there was a significant age increase in food balance choice. 4) Children’s knowledge of food balance grows with age, but urban and rural educational background influence cognitive performance.

学前儿童朴素生物学“理论”的发展——对“生长”认知的实验研究

There is a debate in cognitive development theory on whether cognitive development is general or specific. More and more researchers think that cognitive development is domain specific. People start to investigate preschoolers' native theory of human being's basic knowledge systems. Naive biology is one of the core domains. But there is argument whether there is separate native biological concepts among preschoolers. The research examined preschoolers' cognitive development of naive biological theory on two levels which is "growth" and "aliveness", and it also examined individual difference and factors that lead to the difference. Three studies were designed. Study 1 was to study preschoolers' cognition on growth, which is a basic trait of living things, and whether children can distinguish living and non-living things with the trait and understanding the causality. Study 2 was to investigate preschoolers' distinction between living things and non-living things from an integrated level. Study 3 was to investigate how children make inferences to unfamiliar things with their domain specific knowledge. The results showed the following: 1. Preschoolers gradually developed naive theory of biology on growth level, but their naive theory on integrated level has not developed. 2 Preschoolers' naive theory of biology is not "all or none", 4- and 5-year-old children showed some distinction between living and non-living things to some extent, they use non-intentional reason to explain the cause of growth and their explanation showed coherence. But growth has not been a criteria of ontological distinction of living and non-living things for 4- and 5-year-old children, most 6-year-old children can distinguish between living and non-living things, and these show the developing process of biological cognition. 3. Preschoolers' biological inference is influenced by their domain-specific knowledge, whether they can make inference to new trait of living things depends on whether they have specific knowledge. In the deductive task, children use their knowledge to make inference to unfamiliar things. 4-year-olds use concrete knowledge more often while the 6-year-old use generalized knowledge more frequency. 4. Preschoolers' knowledge grow with age, but individuals' cognitive development speed at different period. Urban and rural educational background affect cognitive performance. As time goes by, the urban-rural knowledge difference to distinguish living and nonliving things reduces. And preschoolers' are at the same developmental stage because the three age groups have similar causal explanation both in quantity and quality. 5. There is intra-individual difference on preschoolers' naive biological cognition. They show different performance on different tasks and domains, and their cognitive development is sequential, they understand growth earlier than they understand "alive", which is an integrated concept. The intra-individual differences decrease with age.

小学儿童空间物体位置编码的实验研究

As a key issue in spatial cognitive developmental research, the coding of object location plays an important role in children's cognitive development. The development of location coding is a precondition for children's adaptation to their environments, and the development of corresponding ability could enhance children's adaptation ability and improve their synthetic diathesis. In this paper, under the improved paradigm of object searching, 7-, 9- and 11-year-olds of urban primary school students were involved in two studies including the total of four experiments. The children were examined upon the ability to encode target location in terms of the distance between two landmarks, three points on a line, the intersection of two lines, or the corresponding points on two parallel lines. The experiments were designed to explore the primary school children's cognitive developmental process upon spatial object location and the correlative restricting factors. From the studies, the following conclusions were drawn: 1)The ability of 7-year-olds to represent target location in terms of the relationships of points and lines is in the inceptive stage and appears unstable. Meanwhile, the same ability of 9-year-olds is in a state of fast developing. The 9-year-olds' performance depends on how difficult the task is. It is stable when task is easy while unstable when task becomes difficult. The ability of 11-year-olds reaches much-developed state and the group's performance is independent of the difficulty of tasks. 2) The correlate coefficient is significant between Raven Standard Inference ability levels and the performance of representing target location in terms of the relationships of points. Those children with good performance in Raven Standard Inference Test have good performance in target location coding. The case is true for all different age groups. As of the task in terms of the relationships of lines, the correlate coefficient between Raven Standard Inference ability levels and children's performance of representing target location is found significant only for the 7-year-olds' group. The case is not true for the groups of 9- and 11-year-olds. It is also found that the correlate coefficient is significant between the sum of performance and Raven Standard Inference ability levels, and that is true for all age groups. 3) Effects from task variable exist upon children's above-mentioned cognitive performance. The effects are different according to different difficulty levels of tasks. Also, they are different according to the different ages. 4) The subjects who failed in the 'no cues for encoding given' situation were able to improve their performances when the cues of encoding were given. Therefore it is possible to improve the primary school children's corresponding cognitive performance by providing the cues of encoding. 5) Two kinds of efficient strategies were used to solve the problem. They are trial-comparison strategy and anticipation-directed strategy.

DOPAMINE D2 RECEPTOR MECHANISMS CONTRIBUTE TO AGE-RELATED COGNITIVE DECLINE - THE EFFECTS OF QUINPIROLE ON MEMORY AND MOTOR-PERFORMANCE IN MONKEYS

The D2 dopamine (DA) receptor agonist, quinpirole, was characterized in young adult monkeys, young reserpine-treated monkeys and aged monkeys to assess the contribution of DA to age-related loss of prefrontal cortical (PFC) cognitive function, Monkeys were tested on a delayed response memory task that depends on the PFC, and a fine motor task that taps the functions of the motor cortex, In young adult monkeys, low quinpirole doses impaired performance of the PFC and fine motor tasks, while higher doses improved memory performance and induced dyskinesias and ''hallucinatory-like'' behaviors. The pattern of the quinpirole response in reserpine-treated monkeys suggested that the impairments in delayed response and fine motor performance resulted from drug actions at D2 autoreceptors, while the improvement in delayed response performance, dyskinesias and ''hallucinatory-like'' behaviors resulted from actions at postsynaptic receptors. In aged monkeys, low doses of quinpirole continued to impair fine motor performance, but lost their ability to impair delayed response performance. The magnitude of cognitive improvement and the incidence of ''hallucinatory-like'' behaviors were also reduced in the aged animals, suggesting some loss of postsynaptic D2 receptor function, The pattern of results is consistent with the greater loss of DA from the PFC than from motor areas in aged monkey brain (Goldman-Rakic and Brown, 1981; Wenk et al., 1989), and indicates that DA depletion contributes significantly to age-related cognitive decline.

RESERPINE IMPAIRS SPATIAL WORKING-MEMORY PERFORMANCE IN MONKEYS - REVERSAL BY THE ALPHA-2-ADRENERGIC AGONIST CLONIDINE

Repeated daily treatment with the catecholamine-depleting agent, reserpine, dramatically reduced performance on the delayed response task, a test of spatial working memory that depends upon the integrity of the prefrontal cortex. Delayed response performance fell from an average of 27.2/30 trials correct before reserpine treatment to an average of 20.4/30 trials correct after repeated reserpine administration. Injection of the alpha2-adrenergic agonist, clonidine (0.0001-0.05 mg/kg), to chronic reserpine-treated monkeys significantly restored performance on the delayed response task; performance after an optimal dose averaged 27.8/30 trials correct. Clonidine's beneficial effects on delayed response performance were longlasting; monkeys remained improved for more than 24 h after a single clonidine injection. The finding that clonidine is efficacious in reserpinized animals supports the hypothesis that alpha2-adrenergic agonists improve cognitive function through actions at postsynaptic, alpha2-adrenergic receptors on non-adrenergic cells. In contrast to the delayed response task, reserpine had little effect on performance of a visual discrimination task, a reference memory task which does not depend on the prefrontal cortex. These results emphasize the importance of postsynaptic alpha2-adrenergic mechanisms in the regulation of working memory,

Improving effects of huperzine A on spatial working memory in aged monkeys and young adult monkeys with experimental cognitive impairment

Our previous studies demonstrated that huperzine A, a reversible and selective acetylcholinesterase inhibitor, exerts beneficial effects on memory deficits in various rodent models of amnesia. To extend the antiamnesic action of huperzine A to nonhuman primates, huperzine A was evaluated for its ability to reverse the deficits in spatial memory produced by scopolamine in young adult monkeys or those that are naturally occurring in aged monkeys using a delayed-response task. Scopolamine, a muscarinic receptor antagonist, dose dependently impaired performance with the highest dose (0.03 mg/kg, i.m.) producing a significant reduction in choice accuracy in young adult monkeys. The delayed performance changed from an average of 26.8/30 trials correct on saline control to an average of 20.2/30 trials correct after scopolamine administration. Huperzine A (0.01-0.1 mg/kg, i.m.) significantly reversed deficits induced by scopolamine in young adult monkeys on a delayed-response task; performance after an optimal dose (0.1 mg/kg) averaged 25.0/30 correct. In four aged monkeys, huperzine A (0.001-0.01 mg/kg, i.m.) significantly increased choice accuracy from 20.5/30 on saline control to 25.2/30 at the optimal dose (0.001 mg/kg for two monkeys and 0.01 mg/kg for the other two monkeys). The beneficial effects of huperzine A on delayed-response performance were long lasting; monkeys remained improved for about 24 h after a single injection of huperzine A. This study extended the findings that huperzine A improves the mnemonic performance requiring working memory in monkeys, and suggests that huperzine A may be a promising agent for clinical therapy of cognitive impairments in patients with Alzheimer's disease.

Disconnection of the hippocampal-prefrontal cortical circuits impairs spatial working memory performance in rats

There is a unidirectional, ipsilateral and monosynaptic projection from the hippocampus to the prefrontal cortex. The cognitive function of hippocampal-prefrontal cortical circuit is not well established. In this paper, we use muscimol treated rats to inv