A window on the ageing brain : Imaging synapses and their dynamics in vivo

The ageing process has an enormous impact on the human body and it represents a major risk factor for a number of diseases. Ageing is also associated with a progressive cognitive decline mainly involving the memory domain. Up to date many studies have investigated the structural and functional changes that occur in the ageing brain. Rather than neuronal loss, it is now widely accepted that synaptic impairments underlie the decreased cognitive performance. Such studies point to reduced synaptic density and plasticity, in specific brain regions, during ageing. However, most studies so far made use of either post-mortem or ex vivo preparations. Thus, the key question addressed in this thesis is to what extent synaptic elements are dynamic in the intact aged brain. A combination of in vivo two-photon imaging, correlated two-photon-electron microscopy and novel computational tools was used to study synaptic boutons in the aged mouse somatosensory cortex. Unexpectedly, circuit-specific increased rates of bouton formation, elimination, and destabilization were found. Age related increased dynamics greatly affected large (i.e., strong) boutons, thought to encode long-term memory, as opposed to smaller ones. The rigorous measurement of the size and location of axonal boutons, achieved for the first time in vivo, showed that while the average density and size of boutons was not affected by ageing, bouton size changes were greater in the aged animals. Such increased size fluctuations were again confined to larger, persistent boutons., Long-term memory impairment, as assessed in a novel behavioural task, was therefore associated with increased, rather than decreased, synaptic destabilization and dynamics, suggesting the existence of a novel mechanism underlying age related cognitive decline.Open Acces

Considerations on incompressibility in Linear Elasticity

The classical way to treat incompressible linear elastic materials is to use the inverse constitutive relationship (strain as a function of the stress), based on the compliance tensor, in place of the direct constitutive equation (stress as a function of strain), based on the elasticity (stiffness) tensor. This is because the elasticity tensor is affected by a diverging bulk modulus, requiring in order to allow the material to sustain any hydrostatic load, and is therefore not defined. In this work we show that there is a part of the elasticity tensor that can be saved also for incompressible materials, by filtering the components that deal with hydrostatic loads. The procedure is based on the treatment of incompressibility by means of the constant of isochoric motion, i.e. of conservation of volume, and fourth-order tensor algebra

Efficient evaluation of the material response of tissues reinforced by statistically oriented fibres

For several classes of soft biological tissues, modelling complexity is in part due to the arrangement of the collagen fibres. In general, the arrangement of the fibres can be described by defining, at each point in the tissue, the structure tensor (i.e. the tensor product of the unit vector of the local fibre arrangement by itself) and a probability distribution of orientation. In this approach, assuming that the fibres do not interact with each other, the overall contribution of the collagen fibres to a given mechanical property of the tissue can be estimated by means of an averaging integral of the constitutive function describing the mechanical property at study over the set of all possible directions in space. Except for the particular case of fibre constitutive functions that are polynomial in the transversely isotropic invariants of the deformation, the averaging integral cannot be evaluated directly, in a single calculation because, in general, the integrand depends both on deformation and on fibre orientation in a non-separable way. The problem is thus, in a sense, analogous to that of solving the integral of a function of two variables, which cannot be split up into the product of two functions, each depending only on one of the variables. Although numerical schemes can be used to evaluate the integral at each deformation increment, this is computationally expensive. With the purpose of containing computational costs, this work proposes approximation methods that are based on the direct integrability of polynomial functions and that do not require the step-by-step evaluation of the averaging integrals. Three different methods are proposed: (a) a Taylor expansion of the fibre constitutive function in the transversely isotropic invariants of the deformation; (b) a Taylor expansion of the fibre constitutive function in the structure tensor; (c) for the case of a fibre constitutive function having a polynomial argument, an approximation in which the directional average of the constitutive function is replaced by the constitutive function evaluated at the directional average of the argument. Each of the proposed methods approximates the averaged constitutive function in such a way that it is multiplicatively decomposed into the product of a function of the deformation only and a function of the structure tensors only. In order to assess the accuracy of these methods, we evaluate the constitutive functions of the elastic potential and the Cauchy stress, for a biaxial test, under different conditions, i.e. different fibre distributions and different ratios of the nominal strains in the two directions. The results are then compared against those obtained for an averaging method available in the literature, as well as against the integration made at each increment of deformation

The linear elasticity tensor of incompressibile materials

With a universally accepted abuse of terminology, materials having much larger stiffness for volumetric than for shear deformations are called incompressible. This work proposes two approaches for the evaluation of the correct form of the linear elasticity tensor of so-called incompressible materials, both stemming from non-linear theory. In the approach of strict incompressibility, one imposes the kinematical constraint of isochoric deformation. In the approach of quasi-incompressibility, which is often employed to enforce incompressibility in numerical applications such as the Finite Element Method, one instead assumes a decoupled form of the elastic potential (or strain energy), which is written as the sum of a function of the volumetric deformation only and a function of the distortional deformation only, and then imposes that the bulk modulus be much larger than all other moduli. The conditions which the elasticity tensor has to obey for both strict incompressibility and quasi-incompressibility have been derived, regardless of the material symmetry. The representation of the linear elasticity tensor for the quasi-incompressible case differs from that of the strictly incompressible case by one parameter, which can be conveniently chosen to be the bulk modulus. Some important symmetries have been studied in detail, showing that the linear elasticity tensors for the cases of isotropy, transverse isotropy and orthotropy are characterised by one, three and six independent parameters, respectively, for the case of strict incompressibility, and two, four and seven independent parameters, respectively, for the case of quasi-incompressibility, as opposed to the two, five and nine parameters, respectively, of the general compressible cas

Structure and reactivity of model oxides related to automobile exhaust catalysis

In this thesis, different ceria and barium oxide based model systems, related to automobile exhaust catalysis, are studied, with the aim of characterizing their structure and reactivity. Chapter 1 is an introduction to the relevance of surface science studies and its cross links with heterogeneous catalysis. The knowledge of a process at atomic scale, which can ultimately be achieved through surface science, can help to improve the design and performance of a material. A description of the techniques used is presented in Chapter 2. The studies of ceria based systems are described in Chapter 3. An introduction to the ceria and oxygen storage capacity (OSC) in ceria containing materials is given. Oxygen adsorption investigations on a CeO2(111) single crystal are presented in the second part. Finally, the preparation and characterisation of CeO2-X layers on a Cu(111) single crystal and, how preparation conditions dictate the ceria overlayer structure and oxidation state, is presented. Chapter 4 concerns the study of oxidised barium layers related to NSR (NOx Storage and Reduction). This involves the preparation of BaOx layers on a Pt(111) single crystal and BaO(100) layers on a Cu(111) single crystal. These layers were exposed to both in situ mixed NO and O2 gases and premixed NO and O2 gases. In the case of BaO(100)/Cu(111), during the latter experiments, nitrite groups could be observed to form on the surface. The preparation of NSR model systems Pt/BaO*/a-Al2O 3(0001) and BaO*/Pt/ct-Al2O3(0001) using traditional, wet chemistry, methods is described in Chapter 5. The model systems were characterised using XPS and air AFM. Finally, the same techniques were used to evaluate NOx storage capabilities of those model systems. Chapter 6 summarises the conclusions