System consolidation of spatial memories in mice: effects of enriched environment.

Environmental enrichment (EE) is known to enhance learning and memory. Declarative memories are thought to undergo a first rapid and local consolidation process, followed by a prolonged process of system consolidation, which consist in a time-dependent gradual reorganization of brain regions supporting remote memory storage and crucial for the formation of enduring memories. At present, it is not known whether EE can affect the process of declarative memory system consolidation. We characterized the time course of hippocampal and cortical activation following recall of progressively more remote spatial memories. Wild-type mice either exposed to EE for 40 days or left in standard environment were subjected to spatial learning in the Morris water maze and to the probe test 1, 10, 20, 30, and 50 days after learning. Following the probe test, regional expression of the inducible immediate early gene c-Fos was mapped by immunohistochemistry, as an indicator of neuronal activity. We found that activation of the medial prefrontal cortex (mPFC), suggested to have a privileged role in processing remote spatial memories, was evident at shorter time intervals after learning in EE mice; in addition, EE induced the progressive activation of a distributed cortical network not activated in non-EE mice. This suggests that EE not only accelerates the process of mPFC recruitment but also recruits additional cortical areas into the network supporting remote spatial memories

Neutralization of nerve growth factor impairs proliferation and differentiation of adult neural progenitors in the subventricular zone

Adult neurogenesis is a multistep process regulated by several extrinsic factors, including neurotrophins. Among them, little is known about the role of nerve growth factor (NGF) in the neurogenic niches of the mouse. Here we analyzed the biology of adult neural stem cells (NSCs) from the subventricular zone (SVZ) of AD11 anti-NGF transgenic mice, in which the expression of the recombinant antibody aD11 leads to a chronic postnatal neutralization of endogenous NGF. We showed that AD11-NSCs proliferate 10-fold less, with respect to their control counterparts, and display a significant impairment in their ability to differentiate into \u3b2-tubulin positive neurons. We found a considerable reduction in the number of SVZ progenitors and neuroblasts also in vivo, which correlates with a lower number of newborn neurons in the olfactory bulbs of AD11 mice and a severe deficit in the ability of these mice to discriminate between different odors. We also demonstrated that, in AD11 mice, the morphology of both SVZ-resident and neurosphere-derived astrocytes is significantly altered. We were able to reproduce the AD11 phenotype in vitro, by acutely treating wild type NSCs with the anti-NGF antibody, further demonstrating that both the proliferation and the differentiation defects are due to the NGF deprivation. Consistently, the proliferative impairment of AD11 progenitors, as well as the atrophic morphology of AD11 astrocytes, can be partly rescued in vitro and in vivo by exogenous NGF addition. Altogether, our results demonstrate a causal link between NGF signaling and proper proliferation and differentiation of neural stem cells from the SVZ.Adult neurogenesis is a multistep process regulated by several extrinsic factors, including neurotrophins. Among them, little is known about the role of nerve growth factor (NGF) in the neurogenic niches of the mouse. Here we analyzed the biology of adult neural stem cells (NSCs) from the subventricular zone (SVZ) of AD11 anti-NGF transgenic mice, in which the expression of the recombinant antibody aD11 leads to a chronic postnatal neutralization of endogenous NGF. We showed that AD11-NSCs proliferate 10-fold less, with respect to their control counterparts, and display a significant impairment in their ability to differentiate into \u3b2-tubulin positive neurons. We found a considerable reduction in the number of SVZ progenitors and neuroblasts also in vivo, which correlates with a lower number of newborn neurons in the olfactory bulbs of AD11 mice and a severe deficit in the ability of these mice to discriminate between different odors. We also demonstrated that, in AD11 mice, the morphology of both SVZ-resident and neurosphere-derived astrocytes is significantly altered. We were able to reproduce the AD11 phenotype in vitro, by acutely treating wild type NSCs with the anti-NGF antibody, further demonstrating that both the proliferation and the differentiation defects are due to the NGF deprivation. Consistently, the proliferative impairment of AD11 progenitors, as well as the atrophic morphology of AD11 astrocytes, can be partly rescued in vitro and in vivo by exogenous NGF addition. Altogether, our results demonstrate a causal link between NGF signaling and proper proliferation and differentiation of neural stem cells from the SVZ

Randomized trial on the effects of a combined physical/cognitive training in aged MCI subjects: the Train the Brain study

Age-related cognitive impairment and dementia are an increasing societal burden. Epidemiological studies indicate that lifestyle factors, e.g. physical, cognitive and social activities, correlate with reduced dementia risk; moreover, positive effects on cognition of physical/cognitive training have been found in cognitively unimpaired elders. Less is known about effectiveness and action mechanisms of physical/cognitive training in elders already suffering from Mild Cognitive Impairment (MCI), a population at high risk for dementia. We assessed in 113 MCI subjects aged 65-89 years, the efficacy of combined physical-cognitive training on cognitive decline, Gray Matter (GM) volume loss and Cerebral Blood Flow (CBF) in hippocampus and parahippocampal areas, and on brain-blood-oxygenation-level-dependent (BOLD) activity elicited by a cognitive task, measured by ADAS-Cog scale, Magnetic Resonance Imaging (MRI), Arterial Spin Labeling (ASL) and fMRI, respectively, before and after 7 months of training vs. usual life. Cognitive status significantly decreased in MCI-no training and significantly increased in MCI-training subjects; training increased parahippocampal CBF, but no effect on GM volume loss was evident; BOLD activity increase, indicative of neural efficiency decline, was found only in MCI-no training subjects. These results show that a non pharmacological, multicomponent intervention improves cognitive status and indicators of brain health in MCI subjects

Laminar flow of a Harschel-Bulkley fluid in channels of finite width

Laminar flow of a viscoplastic fluid in a shallow and wide channel is examined under the long-wave approximation. The fluid is described by the three-parameter Herschel-Bulkley constitutive equation. The complete set of equations governing the flow is presented, generalizing earlier results for a Bingham fluid. The paper then focuses on steady uniform flow: for different geometries of the channel (polynomials like triangular and parabolic, trapezoidal, and rectangular), the velocity distribution and the total discharge are derived analytically as functions of the fluid properties and of the channel cross-section. Results show the existence of dead zones close to bed and banks of the channel; discharges through any given cross-section are higher for dilatant than for pseudo-plastic fluids

Viscous spreading of non-Newtonian gravity currents in radial geometry

A gravity current originated by a power-law viscous fluid propagating in axisymmetric geometry on a horizontal rigid plane below a fluid of lesser density is examined. The intruding fluid is considered to have a pure power-law constitutive equation. The set of equations governing the flow is presented, under the assumption of buoyancy-viscous balance and negligible inertial forces. The conditions under which the above assumptions are valid are examined and a self-similar solution in terms of a nonlinear ordinary differential equation is derived for the release of a fixed volume of fluid. The space-time development of the gravity current is discussed for different flow behavior indexes

Viscous spreading of non-Newtonian gravity currents on a plane

A gravity current originated by a power-law viscous fluid propagating on a horizontal rigid plane below a fluid of lower density is examined. The intruding fluid is considered to have a pure Ostwald power-law constitutive equation. The set of equations governing the flow is presented, under the assumption of buoyancy-viscous balance and negligible inertial forces. The conditions under which the above assumptions are valid are examined and a self-similar solution in terms of a nonlinear ordinary differential equation is derived. For the release of a time-variable volume of fluid, the shape of the gravity current is determined numerically using an approximate analytical solution derived close to the current front as a starting condition. A closed-form analytical expression is derived for the special case of the release of a fixed volume of fluid. The space-time development of the gravity current is discussed for different flow behavior indexes

Scaling Effects on Finite-Domain Fractional Brownian Motion

Power variograms of statistically isotropic or anisotropic fractal fields are weighted integrals of variograms representing statistically homogeneous fields (modes) having mutually uncorrelated increments. Large- and small-scale cutoffs were previ-ously assumed proportional to length scales of the sampling window and data support. We verify this assumption numerically for two-dimensional isotropic fractional Brownian motion (fBm). It was previously concluded semi-empirically that, for Hurst coefficient H = 0.25, the constant of proportionality is μ = 1/3. We confirm this but find μ to vary with mode type and H. We find that due to lack of ergodicity, sample fBm variograms generated on finite windows exhibit directional dependence and differ sharply between realizations. Many realizations are required to obtain an average sample variogram resembling the theoretical power model, especially for persistent fields. We propose generating fBm on finite windows using truncated power variograms and provide guidance for doing so effectively

Generating and scaling fractional Brownian motion on finite domains

Power variograms of statistically isotropic or anisotropic fractal fields (common in earth science) are weighted integrals of variograms representing statistically homogeneous fields (modes) having mutually uncorrelated increments. Large- and small-scale cutoffs were previ-ously assumed proportional to length scales of the sampling window and data support. We verify this assumption numerically for two-dimensional isotropic fractional Brownian motion (fBm). It was previously concluded semi-empirically that, for Hurst coefficient H = 0.25, the constant of proportionality is μ = 1/3. We confirm this but find μ to vary with mode type and H. We find that due to lack of ergodicity, sample fBm variograms generated on finite windows exhibit directional dependence and differ sharply between realizations. Many realizations are required to obtain an average sample variogram resembling the theoretical power model, especially for persistent fields. We propose generating fBm on finite windows using truncated power variograms and provide guidance for doing so effectively