Stochastic and deterministic dynamics of intrinsically irregular firing in cortical inhibitory interneurons

Most cortical neurons fire regularly when excited by a constant stimulus. In contrast, irregular-spiking (IS) interneurons are remarkable for the intrinsic variability of their spike timing, which can synchronize amongst IS cells via specific gap junctions. Here, we have studied the biophysical mechanisms of this irregular spiking in mice, and how IS cells fire in the context of synchronous network oscillations. Using patch-clamp recordings, artificial dynamic conductance injection, pharmacological analysis and computational modeling, we show that spike time irregularity is generated by a nonlinear dynamical interaction of voltage-dependent sodium and fast-inactivating potassium channels just below spike threshold, amplifying channel noise. This $\textit{active irregularity}$ may help IS cells synchronize with each other at gamma range frequencies, while resisting synchronization to lower input frequencies.Biotechnology and Biological Sciences Research Council, Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, Cambridge Overseas Trus

Unravelling the drivers of variability in body condition and reproduction of the European sardine along the Atlantic-Mediterranean transition

Body condition and reproduction data are broadly used to assess the health status of fish because of its implications for recruitment and ecosystem structure. Sardina pilchardus is a small pelagic distributed throughout both Mediterranean and Eastern Atlantic. Seasonal trend analysis of energy storage and reproduction was carried out in sardines from two areas along the Atlantic-Mediterranean transition: Southern Portugal-Gulf of Cádiz (POR-GC) (Atlantic Ocean) and Alboran Sea (Alb) (Mediterranean Sea) from 2019 to 2021. Energetic condition was estimated using tissue and mesenteric fat content, hepatosomatic index (HSI), and the relative condition factor (Kn). Sex, reproductive developmental stage, and gonadosomatic index (GSI) were also obtained. In addition, the oceanographic and meteorological characteristics of the areas were analysed. Results showed that seasonal Kn, tissue and mesenteric fat content, and HSI values of POR-GC specimens exceeded Alb's with summer arrival, period in which sardine acquires reserves to allocate them to reproduction. These differences could be associated to greater productivity of the former area mainly due to rivers discharges and trade winds intensification during summer (from July to September). Furthermore, gonad maturation of POR-GC stock occurred before the Alb. However, no spawning capable individuals were identified until February in POR-GC. In contrast, in Alb it was observed a remarkable fraction of spawning capable and active spawner individuals in October. We hypothesized the migration of mature individuals from POR-GC to the spawning areas located in the Alb. Seasonal genetic population studies are required to untangle it and reliably evaluate the environmental effect on the stocks.En prens

Diseño y desarrollo de una aplicación de escritorio como soporte para la toma de decisiones de zonas de control en la asignación de las ayudas agrarias

El control de las ayudas agrarias es imprescindible dentro del contexto normativo de la agricultura europea. Los procesos de control que realizan las administraciones públicas se basan, en gran medida, en visitas de campo a zonas concretas que varían anualmente en función de factores definidos para cada campaña. Esta metodología origina una movilización importante de personal y equipos que redunda en altos costes económicos y temporales, lo que implica que las zonas elegidas para el control sean las más óptimas posibles para rentabilizar al máximo el trabajo. Esta necesidad de optimización pone de manifiesto la necesidad de automatizar la selección de las zonas, tal que los criterios que intervengan en el proceso sean valorados de forma objetiva e imparcial atendiendo a parámetros que aparecen regulados en la normativa vigente. Este marco planteado es idóneo para el desarrollo y empleo de un SIG que permita de manera automática, sistemática y objetiva la selección de dichas zonas mediante una evaluación multicriterio. El objetivo de este trabajo es el desarrollo de una aplicación de escritorio adaptada a unas necesidades particulares, empleando librerías de código libre para determinar las zonas de control mediante una evaluación multicriterio.The control of agricultural aid is essential in the context of European agricultural policy. The control processes carried out by the government are based on field visits to specific areas, such areas change annually depending on factors for each campaign. This methodology results in a significant mobilization of personnel and equipement causing high economic costs and time, which means that the areas chosen for the control must be the most optimal possible to maximize the job. The need for optimization emphasizes the need to automate the selection of areas, such that the criteria involved in the process must be evaluated objectively and impartially on the basis of parameters present in the regulations. The framework proposed is suitable for the development and use of a GIS to automatically enable, the systematic and objective selection of these areas through a multi-criteria evaluation. The aim of this study is to develop a desktop application adapted to some particular needs, using open source libraries to identify areas of control via a multicriteria evaluation

Chicamocha Canyon Geopark project: A novel strategy for the socio-economic development of Santander (Colombia) through geoeducation, geotourism and geoconservation

The proposed Chicamocha Canyon Geopark project is starting its way for nomination as a UNESCO Global Geopark under the recognition of the Global Geoparks Network. This paper aims to present the justifications of establishing this geopark. It also assesses the potential role of a geopark figure in Santander as an urgent measure to promote the geoconservation of the Chicamocha Canyon territory. The success of this project will not only improve the living conditions of local communities, but also will be a reference model in terms of geological conservation at national and international level. The Chicamocha Canyon, where is proposed to develop this project, has a great potential for the development of the tourism industry due to climatic conditions of the region, besides possessing a rich cultural and natural heritage that needs to be enhanced and protected. Undoubtedly, this initiative should satisfy all the requirements to be a UNESCO Global Geopark, which include a delimited area that defines a territory, the occurrence of geological features of international importance with scientific, educational and aesthetic value, the presence of other types of heritage such as archaeological sites, as well as a proper access infrastructure that favors the socio-economic development of the region. In order to guarantee the successful consolidation of the proposed geopark within the defined territory, this initiative must count the strong support of the local communities and must involve stakeholders such as government authorities, academic and research institutions, and local businesses

Kinematic Parameters That Can Discriminate in Levels of Functionality in the Six-Minute Walk Test in Patients with Heart Failure with a Preserved Ejection Fraction

It is a challenge to manage and assess heart failure with preserved left ventricular ejection fraction (HFpEF) patients. Six-Minute Walk Test (6MWT) is used in this clinical population as a functional test. The objective of the study was to assess gait and kinematic parameters in HFpEF patients during the 6MWT with an inertial sensor and to discriminate patients according to their performance in the 6MWT: (1) walk more or less than 300 m, (2) finish or stop the test, (3) women or men and (4) fallen or did not fall in the last year. A cross-sectional study was performed in patients with HFpEF older than 70 years. 6MWT was carried out in a closed corridor larger than 30 m. Two Shimmer3 inertial sensors were used in the chest and lumbar region. Pure kinematic parameters analysed were angular velocity and linear acceleration in the three axes. Using these data, an algorithm calculated gait kinematic parameters: total distance, lap time, gait speed and step and stride variables. Two analyses were done according to the performance. Student’s t-test measured differences between groups and receiver operating characteristic assessed discriminant ability. Seventy patients performed the 6MWT. Step time, step symmetry, stride time and stride symmetry in both analyses showed high AUC values (>0.75). More significant differences in velocity and acceleration in the maximum Y axis or vertical movements. Three pure kinematic parameters obtained good discriminant capacity (AUC > 0.75). The new methodology proved differences in gait and pure kinematic parameters that can distinguish two groups according to the performance in the 6MWT and they had discriminant capacity.This work was supported by the Spanish Foundation of Internal Medicine, through the call “Prof. Dr. Miguel Vilardell 2019 research project”, grant number: FEMI-PB-PI-MV-2019. Partial funding for open access charge: Universidad de Málaga

Wild-Type, but Not Mutant N296H, Human Tau Restores Aβ-Mediated Inhibition of LTP in Tau−/− mice

Microtubule associated protein tau (MAPT) is involved in the pathogenesis of Alzheimer’s disease and many forms of frontotemporal dementia (FTD). We recently reported that Aβ-mediated inhibition of hippocampal long-term potentiation (LTP) in mice requires tau. Here, we asked whether expression of human $MAPT$ can restore Aβ-mediated inhibition on a mouse $Tau−/−$ background and whether human tau with an FTD-causing mutation (N296H) can interfere with Aβ-mediated inhibition of LTP. We used transgenic mouse lines each expressing the full human $MAPT$ locus using bacterial artificial chromosome technology. These lines expressed all six human tau protein isoforms on a $Tau−/−$ background. We found that the human wild-type $MAPT$ H1 locus was able to restore Aβ$_{42}$-mediated impairment of LTP. In contrast, Aβ$_{42}$ did not reduce LTP in slices in two independently generated transgenic lines expressing tau protein with the mutation N296H associated with frontotemporal dementia (FTD). Basal phosphorylation of tau measured as the ratio of AT8/Tau5 immunoreactivity was significantly reduced in N296H mutant hippocampal slices. Our data show that human $MAPT$ is able to restore Aβ$_{42}$-mediated inhibition of LTP in $Tau−/−$ mice. These results provide further evidence that tau protein is central to Aβ-induced LTP impairment and provide a valuable tool for further analysis of the links between Aβ, human tau and impairment of synaptic function.MVC was supported by a Wellcome Trust OXION Training Fellowship and an equipment grant from Alzheimer’s Research UK. MVC is funded by the Institute for Life Sciences University of Southampton. RW-M was supported by a Wellcome Trust Research Career Development Fellowship (073141/Z/03/Z), CurePSP and the Alzheimer’s Society; FD held a Wellcome Trust DPhil in Neuroscience (075406/Z/04/A), and CMP is funded by the Gerald Kerkut Trust and IfLS. We thank Hana N. Dawson and Michael P. Vitek for Tau−/− mice. We thank Jenny Dworzak for her participation at an early phase of this project

Emergence of synaptic and cognitive impairment in a mature-onset APP mouse model of Alzheimer's disease

The synaptic changes underlying the onset of cognitive impairment in Alzheimer’s disease (AD) are poorly understood. In contrast to the well documented inhibition of long-term potentiation (LTP) in CA3-CA1 synapses by acute Aβ application in adult neurons from rodents, young amyloid precursor protein (APP) transgenic mouse models often, surprisingly, show normal LTP. This suggests that there may be important differences between mature-onset and developmental-onset APP expression/ Aβ accumulation and the ensuing synaptic and behavioural phenotype. Here, in agreement with previous studies, we observed that developmental expression of APPSw,Ind (3–4 month old mice from line 102, PLoS Med 2:e355, 2005), resulted in reduced basal synaptic transmission in CA3-CA1 synapses, normal LTP, impaired spatial working memory, but normal spatial reference memory. To analyse early Aβ-mediated synaptic dysfunction and cognitive impairment in a more mature brain, we used controllable mature-onset APPSw,Ind expression in line 102 mice. Within 3 weeks of mature-onset APPSw,Ind expression and Aβ accumulation, we detected the first synaptic dysfunction: an impairment of LTP in hippocampal CA3-CA1 synapses. Cognitively, at this time point, we observed a deficit in short-term memory. A reduction in basal synaptic strength and deficit in long-term associative spatial memory were only evident following 12 weeks of APPSw,Ind expression. Importantly, the plasticity impairment observed after 3 weeks of mature-onset APP expression is reversible. Together, these findings demonstrate important differences between developmental and mature-onset APP expression. Further research targeted at this early stage of synaptic dysfunction could help identify mechanisms to treat cognitive impairment in mild cognitive impairment (MCI) and early AD