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

Swimming direction reversal of flagella through ciliary motion of mastigonemes.

Bio-inspired designs can provide an answer to engineering problems such as swimming strategies at the micron or nano-scale. Scientists are now designing artificial micro-swimmers that can mimic flagella-powered swimming of micro-organisms. In an application such as lab-on-a-chip in which micro-object manipulation in small flow geometries could be achieved by micro-swimmers, control of the swimming direction becomes an important aspect for retrieval and control of the micro-swimmer. A bio-inspired approach for swimming direction reversal (a flagellum bearing mastigonemes) can be used to design such a system and is being explored in the present work. We analyze the system using a computational framework in which the equations of solid mechanics and fluid dynamics are solved simultaneously. The fluid dynamics of Stokes flow is represented by a 2D Stokeslets approach while the solid mechanics behavior is realized using Euler-Bernoulli beam elements. The working principle of a flagellum bearing mastigonemes can be broken up into two parts: (1) the contribution of the base flagellum and (2) the contribution of mastigonemes, which act like cilia. These contributions are counteractive, and the net motion (velocity and direction) is a superposition of the two. In the present work, we also perform a dimensional analysis to understand the underlying physics associated with the system parameters such as the height of the mastigonemes, the number of mastigonemes, the flagellar wave length and amplitude, the flagellum length, and mastigonemes rigidity. Our results provide fundamental physical insight on the swimming of a flagellum with mastigonemes, and it provides guidelines for the design of artificial flagellar systems.

The rhythm of fountains: The length and time scales of rise height fluctuations at low and high Froude numbers

The magnitude and frequency of vertical fluctuations of the top of an axisymmetric miscible Boussinesq fountain forms the focus of this work. We present measurements of these quantities for saline-aqueous fountains in uniform quiescent surroundings. Our results span source Froude numbers 0.3 ≤ Fr 0 ≤ 40 and, thereby, encompass very weak, weak, intermediate and forced classes of fountain. We identify distinct scalings, based on known quantities at the fountain source, for the frequency of fountain height fluctuations which collapse our data within bands of Fr0. Notably, our scalings reveal that the (dimensionless) frequency takes a constant value within each band. These results highlight characteristic time scales for the fluctuations which we decompose into a single, physically apparent, length scale and velocity scale within each band. Moreover, within one particular band, spanning source Froude numbers towards the lower end of the full range considered, we identify unexpectedly long-period fluctuations indicating a near balance of inertia and (opposing) buoyancy at the source. Our analysis identifies four distinct classes of fluctuation behaviour (four bands of Fr 0) and this classification matches well with existing classifications of fountains based on rise heights. As such, we show that an analysis of the behaviour of the fountain top alone, rather than the entire fountain, provides an alternative approach to classifying fountains. The similarity of classifications based on the two different methods confirms that the boundaries between classes mark tangible changes in the physics of fountains. For high Fr0 we show that the dominant fluctuations occur at the scale of the largest eddies which can be contained within the fountain near its top. Extending this, we develop a Strouhal number, Strtop, based on experimental measures of the fountain top, defined such that Strtop = 1 would suggest the dominant fluctuations are caused by a continual cycle of eddies forming and collapsing at this largest physical scale. For high- Fr 0 fountains we find Strtop ≈ 0. 9. © 2013 Cambridge University Press.

The interaction of riblets with wall-bounded turbulence

The purpose of this thesis is to give answer to the question: why do riblets stop working for a certain size? Riblets are small surface grooves aligned in the mean direction of an overlying turbulent flow, designed specifically to reduce the friction between the flow and the surface. They were inspired by biological surfaces, like the oriented denticles in the skin of fastswimming sharks, and were the focus of a significant amount of research in the late eighties and nineties. Although it was found that the drag reduction depends on the riblet size scaled in wall units, the physical mechanisms implicated have not been completely understood up to now. It has been explained how riblets of vanishing size interact with the turbulent flow, producing a change in the drag proportional to their size, but that is not the regime of practical interest. The optimum performance is achieved for larger sizes, once that linear behavior has broken down, but before riblets begin adopting the character of regular roughness and increasing drag. This regime, which is the most relevant from a technological perspective, was precisely the less understood, so we have focused on it. Our efforts have followed three basic directions. First, we have re-assessed the available experimental data, seeking to identify common characteristics in the optimum regime across the different existing riblet geometries. This study has led to the proposal of a new length scale, the square root of the groove crosssection, to substitute the traditional peak-to-peak spacing. Scaling the riblet dimension with this length, the size of breakdown of the linear behavior becomes roughly universal. This suggests that the onset of the breakdown is related to a certain, fixed value of the cross-section of the groove. Second, we have conducted a set of direct numerical simulations of the turbulent flow over riblets, for sizes spanning the full drag reduction range. We have thus been able to reproduce the gradual transition between the different regimes. The spectral analysis of the flows has proven particularly fruitful, since it has made possible to identify spanwise rollers immediately above the riblets, which begin to appear when the riblet size is close to the optimum. This is a quite surprising feature of the flow, not because of the uniqueness of the phenomenon, which had been reported before for other types of complex and porous surfaces, but because most previous studies had focused on the detail of the flow above each riblet as a unit. Our novel approach has provided the adequate tools to capture coherent structures with an extended spanwise support, which interact with the riblets not individually, but collectively. We have also proven that those spanwise structures are responsible for the increase in drag past the viscous breakdown. Finally, we have analyzed the stability of the flow with a simplified model that connects the appearance of rollers to a Kelvin–Helmholtz-like instability, as is the case also for the flow over plant canopies and porous surfaces. In spite of the model emulating the presence of riblets only in an averaged, general fashion, it succeeds to capture the essential attributes of the breakdown, and provides a theoretical justification for the scaling with the groove cross-section.

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.