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,

Dose-dependent effects of the dopamine D1 receptor agonists A77636 or SKF81297 on spatial working memory in aged monkeys

With advancing age, monkeys develop deficits in spatial working memory resembling those induced by lesions of the prefrontal cortex (PFC). Aged monkeys also exhibit marked loss of dopamine from the PFC, a transmitter known to be important for proper PFC cognitive function. Previous results suggest that D1 agonist treatment can improve spatial working memory abilities in aged monkeys. However, this research was limited by the use of drugs with either partial agonist actions or significant D2 receptor actions. In our study, the selective dopamine D1 receptor full agonists A77636 and SKF81297 were examined in aged monkeys for effects on the working memory functions of the PFC. Both compounds produced a significant, dose-related effect on delayed response performance without evidence of side effects: low doses improved performance although higher doses impaired or had no effect on performance. Both the improvement and impairment in performance were reversed by pretreatment with the D1 receptor antagonist, SCH23390. These findings are consistent with previous results demonstrating that there is a narrow range of D1 receptor stimulation for optimal PFC cognitive function, and suggest that very low doses of D1 receptor agonists may have cognitive-enhancing actions in the elderly.

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.

Effect of huperzine A on working memory in reserpine- or yohimbine-treated monkeys

The effect of huperzine A, a reversible and selective acetylcholinesterase inhibitor, on reserpine- or yohimbine-induced spatial working memory deficits in monkeys has been examined using the delayed response task that depends on the integrity of prefront

Extract of Ginkgo biloba leaves reverses yohimbine-induced spatial working memory deficit in rats

Extract of Ginkgo biloba is used to alleviate age-related decline in cognitive function, which may be associated with the loss of catecholamines in the prefrontal cortex. The purpose of this study was to verify whether alpha-2 adrenergic activity is involved in the facilitative effects of extract of Ginkgo biloba on prefrontal cognitive function. Male Wistar rats were trained to reach criterion in the delayed alternation task (0, 25, and 50-s delay intervals). A pilot study found that 3 or 4 mg/kg of yohimbine (intraperitoneal) reduced the choice accuracy of the delayed alternation task in a dose and delay-dependent manner, without influencing motor ability or perseverative behaviour. Acute oral pre-treatment with doses of 50, 100, or 200 mg/kg (but not 25 mg/kg) of extract of Ginkgo biloba prevented the reduction in choice accuracy induced by 4 mg/kg yohimbine. These data suggest that the prefrontal cognition-enhancing effects of extract of Ginkgo biloba are related to its actions on alpha-2-adrenoceptors.

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

The effects of centrally administered fluorocitrate via inhibiting glial cells on working memory in rats

Although prefrontal and hippocampal neurons are critical for spatial working memory, the function of glial cells in spatial working memory remains uncertain. In this study we investigated the function of glial cells in rats' working memory. The glial cell

Tomorrow's cities - a framework for building resilience

Urbanisation is the great driving force of the twenty-first century. Cities are associated with both productivity and creativity, and the benefits offered by closely connected and high density living and working contribute to sustainability. At the same time, cities need extensive infrastructure – like water, power, sanitation and transportation systems – to operate effectively. Cities therefore comprise multiple components, forming both static and dynamic systems that are interconnected directly and indirectly on a number of levels, all forming the backdrop for the interaction of people and processes. Bringing together large numbers of people and complex products in rich interactions can lead to vulnerability from hazards, threats and even trends, whether natural hazards, epidemics, political upheaval, demographic changes, economic instability and/or mechanical failures; The key to countering vulnerability is the identification of critical systems and clear understanding of their interactions and dependencies. Critical systems can be assessed methodically to determine the implications of their failure and their interconnectivities with other systems to identify options. The overriding need is to support resilience – defined here as the degree to which a system or systems can continue to function effectively in a changing environment. Cities need to recognise the significance of devising adaptation strategies and processes to address a multitude of uncertainties relating to climate, economy, growth and demography. In this paper we put forward a framework to support cities in understanding the hazards, threats and trends that can make them vulnerable to unexpected changes and unpredictable shocks. The framework draws on an asset model of the city, in which components that contribute to resilience include social capital, economic assets, manufactured assets, and governance. The paper reviews the field, and draws together an overarching framework intended to help cities plan a robust trajectory towards increased resilience through flexibility, resourcefulness and responsiveness. It presents some brief case studies demonstrating the applicability of the proposed framework to a wide variety of circumstances.

Silicon on insulator thermodiode with extremely wide working temperature range

This paper presents for the first time the performance of a silicon-on-insulator (SOI) p-n thermodiode, which can operate in an extremely wide temperature range of 200°C to 700°C while maintaining its linearity. The thermodiode is embedded in a thin dielectric membrane underneath a tungsten microheater, which allows the diode characterization at very high temperature (> 800°C). The effect of the junction area (Aj) on the thermodiode linearity, sensitivity and self-heating is experimentally and theoretically investigated. Results on the long-term diode stability at high temperature are also reported. © 2013 IEEE.

Factorial comparison of working memory models.

Three questions have been prominent in the study of visual working memory limitations: (a) What is the nature of mnemonic precision (e.g., quantized or continuous)? (b) How many items are remembered? (c) To what extent do spatial binding errors account for working memory failures? Modeling studies have typically focused on comparing possible answers to a single one of these questions, even though the result of such a comparison might depend on the assumed answers to both others. Here, we consider every possible combination of previously proposed answers to the individual questions. Each model is then a point in a 3-factor model space containing a total of 32 models, of which only 6 have been tested previously. We compare all models on data from 10 delayed-estimation experiments from 6 laboratories (for a total of 164 subjects and 131,452 trials). Consistently across experiments, we find that (a) mnemonic precision is not quantized but continuous and not equal but variable across items and trials; (b) the number of remembered items is likely to be variable across trials, with a mean of 6.4 in the best model (median across subjects); (c) spatial binding errors occur but explain only a small fraction of responses (16.5% at set size 8 in the best model). We find strong evidence against all 6 documented models. Our results demonstrate the value of factorial model comparison in working memory.

"Plateau"-related summary statistics are uninformative for comparing working memory models.

Performance on visual working memory tasks decreases as more items need to be remembered. Over the past decade, a debate has unfolded between proponents of slot models and slotless models of this phenomenon (Ma, Husain, Bays (Nature Neuroscience 17, 347-356, 2014). Zhang and Luck (Nature 453, (7192), 233-235, 2008) and Anderson, Vogel, and Awh (Attention, Perception, Psychophys 74, (5), 891-910, 2011) noticed that as more items need to be remembered, "memory noise" seems to first increase and then reach a "stable plateau." They argued that three summary statistics characterizing this plateau are consistent with slot models, but not with slotless models. Here, we assess the validity of their methods. We generated synthetic data both from a leading slot model and from a recent slotless model and quantified model evidence using log Bayes factors. We found that the summary statistics provided at most 0.15 % of the expected model evidence in the raw data. In a model recovery analysis, a total of more than a million trials were required to achieve 99 % correct recovery when models were compared on the basis of summary statistics, whereas fewer than 1,000 trials were sufficient when raw data were used. Therefore, at realistic numbers of trials, plateau-related summary statistics are highly unreliable for model comparison. Applying the same analyses to subject data from Anderson et al. (Attention, Perception, Psychophys 74, (5), 891-910, 2011), we found that the evidence in the summary statistics was at most 0.12 % of the evidence in the raw data and far too weak to warrant any conclusions. The evidence in the raw data, in fact, strongly favored the slotless model. These findings call into question claims about working memory that are based on summary statistics.

Quantum well infrared photodetector simultaneously working in two atmospheric windows

We have demonstrated a two-contact quantum well infrared photodetector (QWIP) exhibiting simultaneous photoresponse in both the mid- and the long-wavelength atmospheric windows of 3-5 mu m and of 8-12 mu m. The structure of the device was achieved by sequentially growing a mid-wavelength QWIP part followed by a long-wavelength QWIP part separated by an n-doped layer. Compared with the conventional dual-band QWIP device utilizing three ohmic contacts, our QWIP is promising to greatly facilitate two-color focal plane array (FPA) fabrication by reducing the number of the indium bumps per pixel from three to one just like a monochromatic FPA fabrication and to increase the FPA fill factor by reducing one contact per pixel; another advantage may be that this QWIP FPA boasts broadband detection capability in the two atmospheric windows while using only a monochromatic readout integrated circuit. We attributed this simultaneous broadband detection to the different distributions of the total bias voltage between the mid- and long-wavelength QWIP parts.

Two-color quantum well infrared photodetector simultaneously working at 10-14 mu m

We have demonstrated a two-color quantum well infrared photodetector (QWIP) exhibiting simultaneous photoresponse with cutoff wavelengths at 11.8 and 14.5 mu m, respectively. Strong photocurrent signals are observed at temperature of 77 K. The simultaneous two-color photoresponse is achieved by utilizing a simple design by broadening the width of the quantum well and selecting an appropriate doping density. The two peaks are attributed to the intersubband transitions from the ground state to the first excited state (bound state) and to the fifth excited state (continuum state), respectively.

Electrochemiluminescent microoptoprobe with mini-grid working electrode and self-contained sample container

A new electrochemiluminescence (ECL) microoptoprobe with simple structure. small sampling volume and high efficiency was developed. It was constructed by fixing the transparent gold mini-grid on the end surface of the optical fiber, and by surrounding the fiber with the counter- and reference electrodes to form a self-contained three-electrode system. The use of mini-grid electrode increased the surface area and collection efficiency. which resulted in higher ECL signal and better sensitivity. The counter electrode together with one end of the fiber formed a mini-vessel, which eliminated the need of additional container and allowed to perform ECL detection in a very small volume (about 10 mul). The microoptoprobe obtained was characterized with the Ru(bpy)(3)(2-)-tripropylamine system and was applied for the determination of oxalate and chlorpromazine (CPZ). Detection limits (S/N = 3) were 5 x 10(-7) and 1 x 10(-6) mol l(-1) for oxalate and CPZ. respectively. The linear range for oxalate and CPZ extended from 1 x 10(-6) to 1 x 10(-3) mol l(-1), and from 5 x 10(-6) to 5 x 10(-4) mol l(-1). respectively.