The circuit and synaptic organization of the basal ganglia output : mechanistic insights on movement disorders and action control

Understanding the neural circuitry underlying movement is a neuroscientific challenge that promises to help refining currently available treatments for movement disorders. Key structures for movement and action control are the basal ganglia nuclei, whose complexity has only just started to be resolved. The constituent papers of this thesis analyzed different levels of basal ganglia circuit organization and function. In paper 1 we used a 6-hydroxydopamine (6-OHDA) lesion model of Parkinson’s Disease (PD) to study glutamatergic synapses in the substantia nigra reticulata (SNr). We found that NMDA receptors synaptic function in the SNr is altered in 6-OHDA lesioned mice. NMDA receptor blockade transiently rescued hypolocomotion in 6-OHDA lesioned mice. In paper 2 we used a mutated Leucin Rich Repeat Kinase 2 (LRRK2-G2019S) mouse model and studied midbrain adaptations in a middle age range that precedes the onset of neurodegeneration. LRRK2-G2019S mice had increased exploratory behavior compared to their wild-type littermate. In midbrain dopamine neurons glutamatergic neurotransmission was affected in a region-specific manner, but no change in firing was identified. In paper 3 we used the same model to investigate the firing and glutamatergic synapses of SNr neurons. We found no change in firing whereas glutamate release but not N-Methyl-D-Aspartate (NMDA) receptors was altered in SNr neurons. In paper 4 we analyzed the organization of synaptic inputs to the associative and sensorimotor SNr. We found that inputs from the direct pathway are homogeneously distributed across SNr subregions whereas inputs from the indirect pathway are biased to the sensorimotor SNr. In alcohol exposed mice, inputs from the sensorimotor striatum were selectively potentiated. In paper 5 we focused on the indirect pathway projections to the globus pallidus external segment and identified distinct mechanisms of presynaptic modulation by cannabinoid 1 (CB1) and GABAB receptors. In summary, we have investigated several basal ganglia circuits and their synaptic adaptations in disease models. We revealed key features of the SNr circuit organization and its adaptations in mouse models of PD. We found that distinct subpopulations of SNr neurons are part of the associative and sensorimotor loops, and that direct and direct pathway inputs are differentially integrated in these neurons. These findings are relevant to understanding how the SNr shapes the behavioral output of the basal ganglia circuits. In mouse models of PD and alcohol use disorder the synaptic inputs to the SNr are reorganized. These findings open novel views and research directions on the functional organization of the basal ganglia output

Chemical-physical agents and biodeteriogens in the alteration of limestones used in coastal historical fortifications

The alteration of rocks is usually due to the chemical-physical processes that are initially established on the outer surface of the stone and gradually proceed towards the inner matrix. The chemical alteration generated by the interaction with atmospheric agents (weathering) involves the transformation of the mineral phases constituting the rock that are less stable in the current climatic conditions. That often leads to the formation of new secondary phases more stable with respect to the alteration. However, among these phases are often present some very soluble and hygroscopic phases (i.e., soluble salts, clay minerals) that cause inner degradation of the rock, due to their physical-mechanical actions (inner crystallization pressure, hydration dilation). In the case of carbonate rocks (limestone, sandstone with carbonate cement, etc.), the dissolution is the more frequent process, especially when the monuments were located within the cities, due to the acid meteoric precipitations (with H2CO3, H2SO4) that lead to the sulfation of carbonate matrix with formation of gypsum, very harmful to the stone. When the rock (e.g., clay-arenaceous limestones) naturally contains hygroscopic phases inside the matrix (i.e., marine salts, phyllosilicates) and they are also porous (> 20%), the physical degradation is accelerated, with decohesion of the mineralogical matrix (between the crystalline granules) and consequent disintegration of the stone. In the rock-atmosphere interaction often occurs the presence of biodeteriogens (plants, fungi, lichens, micro- organisms, etc.), which negatively participate and in various ways in the processes of rock alteration. The research aims to define the chemical-physical alteration factors on the limestones exposed to different bioclimatic and biogeographic contexts (Mediterranean and Atlantic), taking two study-case monuments located in the Italian and in the Portuguese coasts. In the study presented in this paper the preliminary results of the case-study of Cagliari fortifications have been discussed. In the study the different vascular plants present on stone surface and crevices and their different role in the degradation of limestone rocks have been also studied

TRY plant trait database – enhanced coverage and open access

Plant traits - the morphological, anatomical, physiological, biochemical and phenological characteristics of plants - determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait‐based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits - almost complete coverage for ‘plant growth form’. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait–environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives

Multiple ecosystem services from field margin vegetation for ecological sustainability in agriculture: scientific evidence and knowledge gaps

Background: Field margin and non-crop vegetation in agricultural systems are potential ecosystem services providers because they offer semi-natural habitats for both below and above ground animal groups such as soil organisms, small mammals, birds and arthropods that are service supplying units. They are considered as a target area for enhancing farm biodiversity. Methodology: To explore the multiple potential benefits of these semi-natural habitats and to identify research trends and knowledge gaps globally, a review was carried out following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A total of 235 publications from the year 2000 to 2016 in the Scopus and Web of Science databases were reviewed. Results: The literature showed an increasing trend in the number of published articles over time with European studies leading in the proportion of studies conducted, followed by North America, Asia, South America, Africa and Australia. Several functional groups of organisms were studied from field margin and non-crop vegetation around agricultural lands including natural enemies (37%), insect pests (22%), birds (17%), pollinators (16%), soil macro fauna (4%) and small mammals (4%). Ecosystem services derived from the field margin included natural pest regulation, pollination, nutrient cycling and reduced offsite erosion. Some field margin plants were reported to host detrimental crop pests, a major ecosystem dis-service, potentially leading to increased pest infestation in the field. Conclusion: The majority of studies revealed the importance of field margin and non-crop vegetation around arable fields in enhancing ecosystem biodiversity. Promotion of field margin plants that selectively enhance the population of beneficial organisms would support sustainable food security rather than simply boosting plant diversity. Our analyses also highlight that agro-ecological studies remain largely overlooked in some regions

Neuronal Firing and Glutamatergic Synapses in the Substantia Nigra Pars Reticulata of LRRK2-G2019S Mice

Pathogenic mutations in the leucine-rich repeat kinase 2 (LRRK2) gene are frequent causes of familial Parkinson’s Disease (PD), an increasingly prevalent neurodegenerative disease that affects basal ganglia circuitry. The cellular effects of the G2019S mutation in the LRRK2 gene, the most common pathological mutation, have not been thoroughly investigated. In this study we used middle-aged mice carrying the LRRK2-G2019S mutation (G2019S mice) to identify potential alterations in the neurophysiological properties and characteristics of glutamatergic synaptic transmission in basal ganglia output neurons, i.e., substantia nigra pars reticulata (SNr) GABAergic neurons. We found that the intrinsic membrane properties and action potential properties were unaltered in G2019S mice compared to wild-type (WT) mice. The spontaneous firing frequency was similar, but we observed an increased regularity in the firing of SNr neurons recorded from G2019S mice. We examined the short-term plasticity of glutamatergic synaptic transmission, and we found an increased paired-pulse depression in G2019S mice compared to WT mice, indicating an increased probability of glutamate release in SNr neurons from G2019S mice. We measured synaptic transmission mediated by NMDA receptors and we found that the kinetics of synaptic responses mediated by these receptors were unaltered, as well as the contribution of the GluN2B subunit to these responses, in SNr neurons of G2019S mice compared to WT mice. These results demonstrate an overall maintenance of basic neurophysiological and synaptic characteristics, and subtle changes in the firing pattern and in glutamatergic synaptic transmission in basal ganglia output neurons that precede neurodegeneration of dopaminergic neurons in the LRRK2-G2019S mouse model of late-onset PD

Multi-curve HJM modelling for risk management

We present a HJM approach to the projection of multiple yield curves developed to capture the volatility content of historical term structures for risk management purposes. Since we observe the empirical data at daily frequency and only for a finite number of time-to-maturity buckets, we propose a modelling framework which is inherently discrete. In particular, we show how to approximate the HJM continuous time description of the multi-curve dynamics by a Vector Autoregressive process of order one. The resulting dynamics lends itself to a feasible estimation of the model volatility-correlation structure and market risk-premia. Then, resorting to the Principal Component Analysis we further simplify the dynamics reducing the number of covariance components. Applying the constant volatility version of our model on a sample of curves from the Euro area, we demonstrate its forecasting ability through an out-of-sample test

Chemical reactivity of pozzolans from Sardinia for the production of hydraulic limes

The research is aimed at studying the chemical reactivity between lime and volcanic rocks belonging to different Sardinian outcrops, for a use as raw material in the production of hydraulic / pozzolanic limes. On the basis of preliminary geochemical and mineralogical-petrographic investigations, several volcanic rocks with a basic-intermediate to acid composition (substantially from andesitic, to dacitic, to rhyolitic) have been selected and used for to perform laboratory reactivity tests. These rocks differ in the variable content of glass (from 15% to about 95% in volume), due to the presence of secondary minerals, and to physical characteristics (density, porosity, water absorption, etc.). The physical properties are essentially linked to the different compositional incidence of the crystalline, crystal-clastic, lithic (present in some pyroclastic facies), type and quantity of glass phases, to their different methods of installation (conditioned by temperature, chemical composition, grade welding, etc.), and to the different degree of alteration. The results of the investigations on the pozzolan materials (by polarized light microscopy, XRD, SEM, EPMA-WDS, Chapelle test) show that following parameters affect the chemical reactivity of the volcanic products with lime: i) quantity and type of amorphous phases (glass), linked to the different emplacement of volcanic rocks (affected by temperature, chemical composition, welding grade, etc.), ii) compositional incidence of the crystalline phases, crystal-clasts, lithics (these latter present in some pyroclastic facies), iii) alteration grade of the rocks and presence of secondary minerals (e.g., zeolites, phyllosilicates, etc.)

Multi-curve HJM modelling for risk management

We present a HJM approach to the projection of multiple yield curves developed to capture the volatility content of historical term structures for risk management purposes. Since we observe the empirical data at daily frequency and only for a finite number of time-to-maturity buckets, we propose a modelling framework which is inherently discrete. In particular, we show how to approximate the HJM continuous time description of the multi-curve dynamics by a Vector Autoregressive process of order one. The resulting dynamics lends itself to a feasible estimation of the model volatility-correlation structure and market risk-premia. Then, resorting to the Principal Component Analysis we further simplify the dynamics reducing the number of covariance components. Applying the constant volatility version of our model on a sample of curves from the Euro area, we demonstrate its forecasting ability through an out-of-sample test

Development and Chemico-Physical Characterization of Ovine Milk-Based Ingredients for Infant Formulae

The great majority of infant formula (FM) for neonate’s nutrition are produced using ingredients from cow milk. Recently, some countries, such as China and New Zealand, are turning their attention to the use of ovine milk ingredients for FM production. In this study, a pilot plant process has been set up to produce infant formula ingredients from Sarda sheep milk. To meet the nutritional needs of neonates (0–6 and 6–12 months of age) two different liquid milk-derived formulations (IF1 and IF2, respectively) obtained mixing whole milk, skimmed milk, and whey milk ultrafiltration concentrate (retentate) were produced. Compositional analysis of milk, retentate, and the final IFs showed that the two formulations contain elements of nutritional interest, such as well-balanced content of high biological value proteins (casein:whey proteins ratio of 30:70 and 60:40 for IF1 and IF2, respectively), vitamin A, E and B5, cholesterol, minerals, nucleotides, free amino acids and essential fatty acids (n–6:n–3 ~1), compatible with the growth and development needs of neonates. Therefore, the obtained IF1 and IF2 can be proposed as valuable ovine dairy ingredients for FM manufacturing. Further studies will be necessary to verify the adaptability of the developed process from laboratory to industrial scale application