Imaging striatal dopamine release using a nongenetically encoded near infrared fluorescent catecholamine nanosensor.

Neuromodulation plays a critical role in brain function in both health and disease, and new tools that capture neuromodulation with high spatial and temporal resolution are needed. Here, we introduce a synthetic catecholamine nanosensor with fluorescent emission in the near infrared range (1000-1300 nm), near infrared catecholamine nanosensor (nIRCat). We demonstrate that nIRCats can be used to measure electrically and optogenetically evoked dopamine release in brain tissue, revealing hotspots with a median size of 2 µm. We also demonstrated that nIRCats are compatible with dopamine pharmacology and show D2 autoreceptor modulation of evoked dopamine release, which varied as a function of initial release magnitude at different hotspots. Together, our data demonstrate that nIRCats and other nanosensors of this class can serve as versatile synthetic optical tools to monitor neuromodulatory neurotransmitter release with high spatial resolution

A Significant but Rather Mild Contribution of T286 Autophosphorylation to Ca2+/CaM-Stimulated CaMKII Activity

Autophosphorylation of the Ca(2+)/calmodulin (CaM)-dependent protein kinase II (CaMKII) at T286 generates partially Ca(2+)/CaM-independent "autonomous" activity, which is thought to be required for long-term potentiation (LTP), a form of synaptic plasticity thought to underlie learning and memory. A requirement for T286 autophosphorylation also for efficient Ca(2+)/CaM-stimulated CaMKII activity has been described, but remains controversial.In order to determine the contribution of T286 autophosphorylation to Ca(2+)/CaM-stimulated CaMKII activity, the activity of CaMKII wild type and its phosphorylation-incompetent T286A mutant was compared. As the absolute activity can vary between individual kinase preparations, the activity was measured in six different extracts for each kinase (expressed in HEK-293 cells). Consistent with measurements on purified kinase (from a baculovirus/Sf9 cell expression system), CaMKII T286A showed a mildly but significantly reduced rate of Ca(2+)/CaM-stimulated phosphorylation for two different peptide substrates (to ~75-84% of wild type). Additional slower CaMKII autophosphorylation at T305/306 inhibits stimulation by Ca(2+)/CaM, but occurs only minimally for CaMKII wild type during CaM-stimulated activity assays. Thus, we tested if the T286A mutant may show more extensive inhibitory autophosphorylation, which could explain its reduced stimulated activity. By contrast, inhibitory autophosphorylation was instead found to be even further reduced for the T286A mutant under our assay conditions. On a side note, the phospho-T305 antibody showed some basal background immuno-reactivity also with non-phosphorylated CaMKII, as indicated by T305/306A mutants.These results indicate that Ca(2+)/CaM-stimulated CaMKII activity is mildly (~1.2-1.3fold) further increased by additional T286 autophosphorylation, but that this autophosphorylation is not required for the major part of the stimulated activity. This indicates that the phenotype of CaMKII T286A mutant mice is indeed due to the lack of autonomous activity, as the T286A mutant showed no dramatic reduction in stimulated activity

Spine Calcium Transients Induced by Synaptically-Evoked Action Potentials Can Predict Synapse Location and Establish Synaptic Democracy

CA1 pyramidal neurons receive hundreds of synaptic inputs at different distances from the soma. Distance-dependent synaptic scaling enables distal and proximal synapses to influence the somatic membrane equally, a phenomenon called “synaptic democracy”. How this is established is unclear. The backpropagating action potential (BAP) is hypothesised to provide distance-dependent information to synapses, allowing synaptic strengths to scale accordingly. Experimental measurements show that a BAP evoked by current injection at the soma causes calcium currents in the apical shaft whose amplitudes decay with distance from the soma. However, in vivo action potentials are not induced by somatic current injection but by synaptic inputs along the dendrites, which creates a different excitable state of the dendrites. Due to technical limitations, it is not possible to study experimentally whether distance information can also be provided by synaptically-evoked BAPs. Therefore we adapted a realistic morphological and electrophysiological model to measure BAP-induced voltage and calcium signals in spines after Schaffer collateral synapse stimulation. We show that peak calcium concentration is highly correlated with soma-synapse distance under a number of physiologically-realistic suprathreshold stimulation regimes and for a range of dendritic morphologies. Peak calcium levels also predicted the attenuation of the EPSP across the dendritic tree. Furthermore, we show that peak calcium can be used to set up a synaptic democracy in a homeostatic manner, whereby synapses regulate their synaptic strength on the basis of the difference between peak calcium and a uniform target value. We conclude that information derived from synaptically-generated BAPs can indicate synapse location and can subsequently be utilised to implement a synaptic democracy

Thermoelectric generator (TEG) technologies and applications

2021 The Author(s). Nowadays humans are facing difficult issues, such as increasing power costs, environmental pollution and global warming. In order to reduce their consequences, scientists are concentrating on improving power generators focused on energy harvesting. Thermoelectric generators (TEGs) have demonstrated their capacity to transform thermal energy directly into electric power through the Seebeck effect. Due to the unique advantages they present, thermoelectric systems have emerged during the last decade as a promising alternative among other technologies for green power production. In this regard, thermoelectric device output prediction is important both for determining the future use of this new technology and for specifying the key design parameters of thermoelectric generators and systems. Moreover, TEGs are environmentally safe, work quietly as they do not include mechanical mechanisms or rotating elements and can be manufactured on a broad variety of substrates such as silicon, polymers and ceramics. In addition, TEGs are position-independent, have a long working life and are ideal for bulk and compact applications. Furthermore, Thermoelectric generators have been found as a viable solution for direct generation of electricity from waste heat in industrial processes. This paper presents in-depth analysis of TEGs, beginning with a comprehensive overview of their working principles such as the Seebeck effect, the Peltier effect, the Thomson effect and Joule heating with their applications, materials used, Figure of Merit, improvement techniques including different thermoelectric material arrangements and technologies used and substrate types. Moreover, performance simulation examples such as COMSOL Multiphysics and ANSYS-Computational Fluid Dynamics are investigated

Neuron addition and loss in the song system: regulation and function

Neurons continue to be produced and replaced throughout life in songbirds. Proliferation in the walls of the lateral ventricles gives rise to neurons that migrate long distances to populate many diverse telencephalic regions, including nuclei dedicated to the perception and production of song, a learned behavior. Many projection neurons are incorporated into the efferent motor pathway for song control. Replacement of these neurons is regulated, in part, by neuron death. Underlying mechanisms include gonadal steroids and BDNF, but are likely to involve other trophic factors as well. The functional significance of neuronal replacement remains unclear. However, recent experiments suggest a link between cell turnover and one or more specific attributes of song learning and production. Several hypotheses are critically examined, including the possibility that neuronal replacement provides motor flexibility to allow for error correction-a capacity needed for juvenile and adult song learning, but also likely to be important for the maintenance of song stereotypy. We highlight important gaps in our knowledge and discuss future directions that may bring us closer to solving the riddle of why neurons are produced and replaced in adulthood

Ovarian Hormones Organize the Maturation of Inhibitory Neurotransmission in the Frontal Cortex at Puberty Onset in Female Mice

The frontal cortex matures late in development, showing dramatic changes after puberty onset, yet few experiments have directly tested the role of pubertal hormones in cortical maturation. One mechanism thought to play a primary role in regulating the maturation of the neocortex is an increase in inhibitory neurotransmission, which alters the balance of excitation and inhibition. We hypothesized that pubertal hormones could regulate maturation of the frontal cortex by this mechanism. Here, we report that manipulations of gonadal hormones do significantly alter the maturation of inhibitory neurotransmission in the cingulate region of the mouse medial frontal cortex, an associative region that matures during the pubertal transition and is implicated in decision making, learning, and psychopathology. We find that inhibitory neurotransmission, but not excitatory neurotransmission, increases onto cingulate pyramidal neurons during peri-pubertal development and that this increase can be blocked by pre-pubertal, but not post-pubertal, gonadectomy. We next used pre-pubertal hormone treatment to model early puberty onset, a phenomenon increasingly observed in girls living in developed nations. We find that pre-pubertal hormone treatment drives an early increase in inhibitory neurotransmission in the frontal cortex, but not the somatosensory cortex, suggesting that earlier puberty can advance cortical maturation in a regionally specific manner. Pre-pubertal hormone treatment also accelerates maturation of tonic inhibition and performance in a frontal-cortex-dependent reversal-learning task. These data provide rare evidence of enduring, organizational effects of ovarian hormones at puberty and provide a potential mechanism by which gonadal hormones could regulate the maturation of the associative neocortex

Sex Differences in Pubertal Circadian and Ultradian Rhythmic Development Under Semi-naturalistic Conditions.

Biological rhythms in core body temperature (CBT) provide informative markers of adolescent development under controlled laboratory conditions. However, it is unknown whether these markers are preserved under more variable, semi-naturalistic conditions, and whether CBT may therefore prove useful in a real-world setting. To evaluate this possibility, we examined fecal steroid concentrations and CBT rhythms from pre-adolescence (p26) through early adulthood (p76) in intact male and female Wistar rats under natural light and climate at the Stephen Glickman Field Station for the Study of Behavior, Ecology and Reproduction. Despite greater environmental variability, CBT markers of pubertal onset and its rhythmic progression were comparable with those previously reported in laboratory conditions in female rats and extend actigraphy-based findings in males. Specifically, sex differences emerged in CBT circadian rhythm (CR) power and amplitude prior to pubertal onset and persisted into early adulthood, with females exhibiting elevated CBT and decreased CR power compared with males. Within-day (ultradian rhythm [UR]) patterns also exhibited a pronounced sex difference associated with estrous cyclicity. Pubertal onset, defined by vaginal opening, preputial separation, and sex steroid concentrations, occurred later than previously reported under lab conditions for both sexes. Vaginal opening and increased fecal estradiol concentrations were closely tied to the commencement of 4-day oscillations in CBT and UR power. By contrast, preputial separation and the first rise in testosterone concentration were not associated with adolescent changes to CBT rhythms in male rats. Together, males and females exhibited unique temporal patterning of CBT and sex steroids across pubertal development, with tractable associations between hormonal concentrations, external development, and temporal structure in females. The preservation of these features outside the laboratory supports CBT as a strong candidate for translational pubertal monitoring under semi-naturalistic conditions in females

VORONEZH (Rusia). Mapas generales. 1792

Márgenes graduadosLímites de las divisiones administrativas diferenciadas por colorHidrografíaEscala gráfica de 70 vertas [=8 cm]. Coordenadas referidas a un meridiano que no se especifica (E 53°02'00''--E 60°59'00''/N 52°43'03''--N 48°59'00''). Recuadro geográfico de 1° en 1°Título enmarcado en escena, estando escrito en una vela sostenida por figura femenina alegórica con el manto sembrado por el águila bicéfala de los Romanov, que se dirige a un putti, de pie sobre una barca de cuyo palo pende un escudo, probablemente de la ciudad de Voronezh y sobre la cual aparece la inicial "P" (de Pedro I el Grande) rodeada de una aureola a cuyo lado se ve un ángel trompetero con bandera y filacteria con la fecha "1686". Consta el grabador: "I. C. Nabholz sculpt."Abundante toponimiaCopia digital. Madrid : Ministerio de Cultura, 2010Fecha de publicación tomada de la atribuida al atlas en: "Tooley's Dictionary of Mapmakers". Tring 1979, p. 388 y otra