University of Lausanne

About: University of Lausanne is a education organization based out in Lausanne, Switzerland. It is known for research contribution in the topics: Population & Medicine. The organization has 20508 authors who have published 46458 publications receiving 1996655 citations. The organization is also known as: Université de Lausanne & UNIL.

Experience-dependent and cell-type-specific spine growth in the neocortex.

Abstract: Functional circuits in the adult neocortex adjust to novel sensory experience, but the underlying synaptic mechanisms remain unknown. Growth and retraction of dendritic spines with synapse formation and elimination could change brain circuits. In the apical tufts of layer 5B (L5B) pyramidal neurons in the mouse barrel cortex, a subset of dendritic spines appear and disappear over days, whereas most spines are persistent for months. Under baseline conditions, new spines are mostly transient and rarely survive for more than a week. Transient spines tend to be small, whereas persistent spines are usually large. Because most excitatory synapses in the cortex occur on spines, and because synapse size and the number of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors are proportional to spine volume, the excitation of pyramidal neurons is probably driven through synapses on persistent spines. Here we test whether the generation and loss of persistent spines are enhanced by novel sensory experience. We repeatedly imaged dendritic spines for one month after trimming alternate whiskers, a paradigm that induces adaptive functional changes in neocortical circuits. Whisker trimming stabilized new spines and destabilized previously persistent spines. New-persistent spines always formed synapses. They were preferentially added on L5B neurons with complex apical tufts rather than simple tufts. Our data indicate that novel sensory experience drives the stabilization of new spines on subclasses of cortical neurons. These synaptic changes probably underlie experience-dependent remodelling of specific neocortical circuits.

Simultaneous enumeration of cancer and immune cell types from bulk tumor gene expression data.

Abstract: Malignant tumors do not only contain cancer cells. Normal cells from the body also infiltrate tumors. These often include a variety of immune cells that can help detect and kill cancer cells. Many evidences suggest that the proportion of different immune cell types in a tumor can affect tumor growth and which treatments are effective. Researchers often study tumors by measuring the expression of genes, i.e., which genes are active in tumors. However, the proportion of different cell types in the tumor is often not measured for tumors studied at the gene expression level. Racle et al. have now demonstrated that a new computer-based tool can accurately detect all the main cell types in a tumor directly from the expression of genes in this tumor. The tool is called “Estimating the Proportion of Immune and Cancer cells” – or EPIC for short. It compares the level of expression of genes in a tumor with a library of the gene expression profiles from specific cell types that can be found in tumors and uses this information to predict how many of each type of cell are present. Experimental measurements of several human tumors confirmed that EPIC’s predictions are accurate. EPIC is freely available online. Since the active genes in tumors from many patients have already been documented together with clinical data, researchers could use EPIC to investigate whether the cell types in a tumor affect how harmful it is or how well a particular treatment works on it. In the future, this information could help to identify the best treatment for a particular patient and may reveal new genes that cause malignant tumors to develop and grow.

Ibotenate lesions of hippocampus and/or subiculum: Dissociating components of allocentric spatial learning.

Abstract: This study examined the effects of ibotenic acid-induced lesions of the hippocampus, subiculum and hippocampus +/- subiculum upon the capacity of rats to learn and perform a series of allocentric spatial learning tasks in an open-field water maze. The lesions were made by infusing small volumes of the neurotoxin at a total of 26 (hippocampus) or 20 (subiculum) sites intended to achieve complete target cell loss but minimal extratarget damage. The regional extent and axon-sparing nature of these lesions was evaluated using both cresyl violet and Fink - Heimer stained sections. The behavioural findings indicated that both the hippocampus and subiculum lesions caused impairment to the initial postoperative acquisition of place navigation but did not prevent eventual learning to levels of performance almost as effective as those of controls. However, overtraining of the hippocampus + subiculum lesioned rats did not result in significant place learning. Qualitative observations of the paths taken to find a hidden escape platform indicated that different strategies were deployed by hippocampal and subiculum lesioned groups. Subsequent training on a delayed matching to place task revealed a deficit in all lesioned groups across a range of sample choice intervals, but the subiculum lesioned group was less impaired than the group with the hippocampal lesion. Finally, unoperated control rats given both the initial training and overtraining were later given either a hippocampal lesion or sham surgery. The hippocampal lesioned rats were impaired during a subsequent retention/relearning phase. Together, these findings suggest that total hippocampal cell loss may cause a dual deficit: a slower rate of place learning and a separate navigational impairment. The prospect of unravelling dissociable components of allocentric spatial learning is discussed.

Long-Term Contracts, Short-Term Investment and Monitoring

Abstract: term contracts, asymmetric information between investors and firms can make it impossible to implement profitable long-term projects. The paper characterizes the structure of optimal, renegotiation-proof contracts for unmonitored and monitored finance. Monitoring by investors, although itself subject to distorting incentive constraints, is shown to be able to overcome the short-term bias of investment and thus to lengthen the firms' planning horizon. I. INTRODUCTION An important question in the literature on corporate finance in the recent years has been whether the dependence on outside finance can force firms to undertake inefficient amounts of investment. Little work has been done, however, on the impact of outside finance on the quality of investment. The present paper studies this issue in the context of a question which has attracted considerable attention in the financial press and in the economic policy debate: can the dependence on outside finance lead a firm to undertake inefficient myopic investments?' To do this, the paper studies a dynamic model of financial contracting that allows one to characterize the choice of a firm's investment horizon. It points to information asymmetries as responsible for investment myopia, discusses the costs and benefits of monitoring as a reaction to it, and characterizes the optimal dynamic debt structure for unmonitored, as well as for monitored finance. According to standard financial theory, the market sees through the corporate veil and encourages the choice of efficient projects. In response to this, an important recent literature has developed more explicit theories of financial contracts and their role for the behaviour of imperfectly informed and strategically acting economic agents.2 This paper builds on this literature and analyses the problem of optimal financial contracting for a firm that wants to raise capital for a risky long-term investment project. The framework used to study the issue is a simple two-period contracting model, complicated by the interplay of hidden-characteristics and hidden-action problems on the side of the firm. More specifically, the probability distribution of project returns is assumed to depend on the intrinsic quality of the project, as well as on the investment horizon and effort chosen