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.

Transcriptome of embryonic and neonatal mouse cortex by high-throughput RNA sequencing

Brain structure and function experience dramatic changes from embryonic to postnatal development. Microarray analyses have detected differential gene expression at different stages and in disease models, but gene expression information during early brain development is limited. We have generated >27 million reads to identify mRNAs from the mouse cortex for>16,000 genes at either embryonic day 18 (E18) or postnatal day 7 (P7), a period of significant synapto-genesis for neural circuit formation. In addition, we devised strategies to detect alternative splice forms and uncovered more splice variants. We observed differential expression of 3,758 genes between the 2 stages, many with known functions or predicted to be important for neural development. Neurogenesis-related genes, such as those encoding Sox4, Sox11, and zinc-finger proteins, were more highly expressed at E18 than at P7. In contrast, the genes encoding synaptic proteins such as synaptotagmin, complexin 2, and syntaxin were up-regulated from E18 to P7. We also found that several neurological disorder-related genes were highly expressed at E18. Our transcriptome analysis may serve as a blueprint for gene expression pattern and provide functional clues of previously unknown genes and disease-related genes during early brain development.

空间及言语工作记忆任务的情绪效应：来自ERP/ fMRI的证据

In the present study, based on processing efficiency theory, we used the event-related potentials (ERP) and functional magnetic resonance image (fMRI) techniques to explore the underlying neutral mechanism of influences of negative emotion on three subsystems of working memory, phonological loop、 visuospatial sketh pad and the central executive. The modified DSMT (delayed matching-to-sample task) and n-back tasks were adopted and IAPS (International Affective Picture System) pictures were employed to induce the expected emotional state of subjects. The main results and conclusions obtained in the series of experiments are as the following: 1. In DSM tasks, we found P200 and P300 were reduced by negative emotion in both spatial and verbal tasks, however the increased negative slow wave were only observed in spatial tasks, not in verbal tasks. 2. In n-back tasks, the updating function of WM associated P300 was affected by negative emotion only in spatial tasks, not in verbal tasks. Current density analysis revealed strong current density in the fronto-parietal cortex only in the spatial tasks as well. 3. We adopted fMRI-block design and ROIs analysis, and found significant emotion and task effects in spatial WM-associated right superior parietal cortex; only emotion effect in verbal WM-associated Broca’s area; the interaction effect in attention-associated medial prefrontal area and bilateral inferior parietal cortex. These results implied the negative emotion mainly disturbed the spatial WM-related areas, and the attention control system play a key role in the interaction of spatial WM and negative emotion. 4. to further examine the effects of positive、negative and neutral emotion on tasks with different cognitive loads, the selective effect of emotion on the ERP components of spatial WM was only found in 2-back tasks, not in visual searching tasks. So, firstly the positive emotion as well as negative emotion selectively disturbed on spatial WM in light of the attention resource competition mechanism. Secondly, the selective influences based on the different WM systems, not the properties of spatial and verbal information. At last, the manner of the interaction of emotion and cognition is correlated with the cognitive load.

基底神经节的认知和记忆功能研究

The cognition and memory functions of the Basal Ganglia have been the focus of contemporary cognitive neuroscience researches. This study, from neuroanatomical and neurophysiological point of view, thoroughly surveyed the recent relevant research progress, carefully examined the evidences of the neurological basis for the Basal Ganglia possessing or participating cognition or memory functions. Moreover, it reviewed recent achievements on the cognitive functions of the basal ganglia based on researches on rodent animals, primate animals and human beings. Then it presented a series of experiments conducted, by neuropsychological and cognitive psychological methods, on neurological patients with focal lesions to the basal ganglia or combining with bilateral hippocampus or thalamus impaired to explore what the role of the basal ganglia play in human explicit and implicit memory. It was found that the lesions to the basal ganglia partially handicapped explicit verbal memory and completely impaired perceptual priming. It was also found that right cerebral cortex dysplasia but basal ganglia spared had no effects on priming tasks performances. The results suggested that the basal ganglia contain or accommodate higher cognitive functions and further suggested that priming be irrelevant to right cerebral cortex. It was posited that the basal ganglia, on the basis of interaction with prefrontal or temporal cortices, mediate movement function as well as cognition and memory functions.