Stimulus Discrimination in Cerebellar Purkinje Neurons

Cerebellar Purkinje neurons fire spontaneously in the absence of synaptic input. Overlaid on this intrinsic activity, excitatory input from parallel fibres can add simple spikes to the output train, whereas inhibitory input from interneurons can introduce pauses. These and other influences lead to an irregular spike train output in Purkinje neurons in vitro and in vivo, supplying a variable inhibitory drive to deep cerebellar nuclear neurons. From a computational perspective, this variability raises some questions, as individual spikes induced by excitatory inputs are indistinguishable from intrinsic firing activity. Although bursts of high-frequency excitatory input could be discriminated unambiguously from background activity, granule neurons are known to fire in vivo over a wide range of frequencies. This would mean that much of the sensory information relayed through the cerebellar cortex would be lost within the random variation in background activity. We speculated that alternative mechanisms for signal discrimination may exist, and sought to identify characteristic motifs within the sequence of spikes that followed stimulation events. We found that under certain conditions, parallel fibre stimulation could reliably add a “couplet” of spikes with an unusually short interspike interval to the output train. Therefore, despite representing a small fraction of the total number of spikes, these signals can be reliably discriminated from background firing on a moment-to-moment basis, and could result in a differential downstream response

Assessing the potential contribution of excess heat from biogas plants towards decarbonising German residential heating

This paper analyses the current technical potential for utilising excess heat from German biogas plants, in order to supply local settlements through district heating. Based on a survey of around 600 biogas plant operators, the fractions of excess heat in these plants are analysed. A heuristic is developed to match biogas plants (heat sources) with local settlements (sinks) in order to determine a least-cost district heating supply for residential buildings. Two criteria are employed, namely the CO2 abatement costs and the payback period, which represent the macro- and microeconomic perspectives respectively. Based on the survey, a mean fraction of 40% excess heat is determined, which is in agreement with other empirical studies. Extrapolating this fraction to the German biogas plant stock leads to technically feasible CO2 savings of around 2.5 MtCO2/a. Employing the criteria of CO2 abatement costs and payback period yields about 2 MtCO2/a below CO2 abatement costs of 200 €/tCO2 and below a payback period of 9 years respectively. This represents about 0.25% of the total German CO2 emissions in 2016 or around 2.5% of all CO2 in residential buildings. If threshold values of 80 €/tCO2 and 5 years are employed, to reflect the German government’s suggested external cost of carbon and an expected payback period from an investor’s point of view respectively, the carbon reduction potential is about 0.5 MtCO2 and 0.75 MtCO2 respectively. These potentials are concentrated in around 3,500 of 11,400 municipalities, where district heating from biogas plants could reduce CO2 emissions per capita by an average of 250 kgCO_2/a and cover 12% of the total heating demand

Probabilistic encoding of stimulus strength in astrocyte global calcium signals

Astrocyte calcium signals can range in size from subcellular microdomains to waves that spread through the whole cell (and into connected cells). The differential roles of such local or global calcium signaling are under intense investigation, but the mechanisms by which local signals evolve into global signals in astrocytes are not well understood, nor are the computational rules by which physiological stimuli are transduced into a global signal. To investigate these questions, we transiently applied receptor agonists linked to calcium signaling to primary cultures of cerebellar astrocytes. Astrocytes repetitively tested with the same stimulus responded with global signals intermittently, indicating that each stimulus had a defined probability for triggering a response. The response probability varied between agonists, increased with agonist concentration, and could be positively and negatively modulated by crosstalk with other signaling pathways. To better understand the processes determining the evolution of a global signal, we recorded subcellular calcium “puffs” throughout the whole cell during stimulation. The key requirement for puffs to trigger a global calcium wave following receptor activation appeared to be the synchronous release of calcium from three or more sites, rather than an increasing calcium load accumulating in the cytosol due to increased puff size, amplitude, or frequency. These results suggest that the concentration of transient stimuli will be encoded into a probability of generating a global calcium response, determined by the likelihood of synchronous release from multiple subcellular sites

Photopharmacologic Vision Restoration Reduces Pathological Rhythmic Field Potentials in Blind Mouse Retina

Photopharmacology has yielded compounds that have potential to restore impaired visual responses resulting from outer retinal degeneration diseases such as retinitis pigmentosa. Here we evaluate two photoswitchable azobenzene ion channel blockers, DAQ and DAA for vision restoration. DAQ exerts its effect primarily on RGCs, whereas DAA induces light-dependent spiking primarily through amacrine cell activation. Degeneration-induced local field potentials remain a major challenge common to all vision restoration approaches. These 5-10 Hz rhythmic potentials increase the background firing rate of retinal ganglion cells (RGCs) and overlay the stimulated response, thereby reducing signal-to-noise ratio. Along with the bipolar cell-selective photoswitch DAD and second-generation RGC-targeting photoswitch PhENAQ, we investigated the effects of DAA and DAQ on rhythmic local field potentials (LFPs) occurring in the degenerating retina. We found that photoswitches targeting neurons upstream of RGCs, DAA (amacrine cells) and DAD (bipolar cells) suppress the frequency of LFPs, while DAQ and PhENAQ (RGCs) had negligible effects on frequency or spectral power of LFPs. Taken together, these results demonstrate remarkable diversity of cell-type specificity of photoswitchable channel blockers in the retina and suggest that specific compounds may counter rhythmic LFPs to produce superior signal-to-noise characteristics in vision restoration

Investigation of the impact of total sleep deprivation at home on the number of intrusive memories to an analogue trauma

Sleep enhances the consolidation of memory; however, this property of sleep may be detrimental in situations where memories of an event can lead to psychopathology, such as following a traumatic event. Intrusive memories of trauma are emotional memories that spring to mind involuntarily and are a core feature of post-traumatic stress disorder. Total sleep deprivation in a hospital setting on the first night after an analogue trauma (a trauma film) led to fewer intrusive memories compared to sleep as usual in one study. The current study aimed to test an extension of these findings: sleep deprivation under more naturalistic conditions-at home. Polysomnographic recordings show inconsistent sleep deprivation was achieved at home. Fewer intrusive memories were reported on day 1 after the trauma film in the sleep-deprived condition. On day 2 the opposite was found: more intrusive memories in the sleep-deprived condition. However, no significant differences were found with the removal of two participants with extreme values and no difference was found in the total number of intrusive memories reported in the week following the trauma film. Voluntary memory of the trauma film was found to be slightly impaired in the sleep deprivation condition. In conclusion, compared to our eariler findings using total sleep deprivation in a hospital setting, in the current study the use of inconsistent sleep deprivation at home does not replicate the pattern of results on reducing the number of intrusive memories. Considering the conditions under which sleep deprivation (naturalistic versus hospital) was achieved requires further examination

Three-body correlation functions and recombination rates for bosons in three and one dimensions

We investigate local three-body correlations for bosonic particles in three and one dimensions as a function of the interaction strength. The three-body correlation function g(3) is determined by measuring the three-body recombination rate in an ultracold gas of Cs atoms. In three dimensions, we measure the dependence of g(3) on the gas parameter in a BEC, finding good agreement with the theoretical prediction accounting for beyond-mean-field effects. In one dimension, we observe a reduction of g(3) by several orders of magnitude upon increasing interactions from the weakly interacting BEC to the strongly interacting Tonks-Girardeau regime, in good agreement with predictions from the Lieb-Liniger model for all strengths of interaction.Comment: 5 figure

Scoping review protocol : is there a role for physical activity interventions in the treatment pathway of bladder cancer?

Introduction Patients with bladder cancer (BC) have been found to have worse experiences than those with other cancers which may partly be due to impact on quality of life. Currently, little is known about the impact of physical activity (PA) on BC outcomes. This scoping review aims to identify what interventions are available, their reported efficacy and feasibility, and a description of potential underlying biological mechanisms for their effects. Methods and analysis Preferred Reporting Items for Systematic Reviews and Meta-Analyses Scoping Review (ScR) guidelines and the Levac methodology framework will be followed/used. Electronic databases will be searched (MEDLINE, EMBASE, the Cochrane Library, PsycInfo and Health, OpenGray). Two independent reviewers will screen all abstracts and titles and during a second stage and full-text publications for inclusion. All studies describing PA (as an existing lifestyle or as part of an intervention programme) during BC management will be included. Study characteristics will be recorded; qualitative data will be extracted and evaluated using the Donabedian framework. Quantitative data will be extracted and summarised. A further consultation step will be carried out with patients, their family members and healthcare professionals

Timing of Optical Maturation of Recently Exposed Material on Ceres

On Ceres, multispectral imaging data from the Dawn spacecraft show a distinct bluish characteristic for recently exposed material from the subsurface in, for example, crater ejecta. Ejecta blankets of presumably old craters show a more reddish spectrum. We selected areas in which fresh material from the Cerean subsurface was exposed at a specific time in the past, and no later geologic process is expected to have changed its surface composition or its cratering record. For each area, we determined two color ratios and the crater retention age. The measured color ratios show an exponential diminishment of the bluish characteristic over time. Although the cause of the color change remains uncertain, the time-dependent change in spectral properties is evident, which could help identify the process

The Reorientation of T-Cell Polarity and Inhibition of Immunological Synapse Formation by CD46 Involves Its Recruitment to Lipid Rafts

Many infectious agents utilize CD46 for infection of human cells, and therapeutic applications of CD46-binding viruses are now being explored. Besides mediating internalization to enable infection, binding to CD46 can directly alter immune function. In particular, ligation of CD46 by antibodies or by measles virus can prevent activation of T cells by altering T-cell polarity and consequently preventing the formation of an immunological synapse. Here, we define a mechanism by which CD46 reorients T-cell polarity to prevent T-cell receptor signaling in response to antigen presentation. We show that CD46 associates with lipid rafts upon ligation, and that this reduces recruitment of both lipid rafts and the microtubule organizing centre to the site of receptor cross-linking. These data combined indicate that polarization of T cells towards the site of CD46 ligation prevents formation of an immunological synapse, and this is associated with the ability of CD46 to recruit lipid rafts away from the site of TCR ligation