Transgenic cross-referencing of inhibitory and excitatory interneuron populations to dissect neuronal heterogeneity in the dorsal horn

The superficial dorsal horn (SDH, LI-II) of the spinal cord receives and processes multimodal sensory information from skin, muscle, joints and viscera then relays it to the brain. Neurons within the SDH fall into two broad categories, projection neurons and interneurons. The later can be further subdivided into excitatory and inhibitory types. Traditionally, interneurons within the SDH have been divided into overlapping groups according to their neurochemical, morphological and electrophysiological properties. Recent clustering analyses, based on molecular transcript profiles of cells and nuclei, have predicted many more functional groups of interneuron than expected using traditional approaches. In this study, we used electrophysiological and morphological data obtained from genetically-identified excitatory (vGLUT2) and inhibitory (vGAT) interneurons in transgenic mice to cluster them into groups sharing common characteristics, and subsequently determined how many clusters will be assigned by combinations of these properties. Consistent with previous reports, we show differences exist between excitatory and inhibitory interneurons in terms of their excitability, nature of ongoing excitatory drive, action potential properties, sub-threshold current kinetics, and morphology. The resulting clusters based on statistical and unbiased assortment of these data fell well short of the numbers of molecularly predicted clusters. There was no clear characteristic that in isolation defined a population, rather multiple variables were needed to predict cluster membership. Importantly though, our analysis highlighted the appropriateness of using transgenic lines as tools to functionally subdivide both excitatory and inhibitory interneuron populations

TMT adaptive optics systems control architecture

Achieving the science goals of TMT will require AO subsystems of unprecedented power and sophistication, including a Real Time Controller (RTC) subsystem that will implement wavefront reconstruction and control algorithms for up to four different laser guide star (LGS) AO systems. The requirements for the RTC represent a significant advance over the current generation of astronomical AO control systems, both in terms of the wavefront reconstruction algorithms to be employed and the new hardware approaches that will be required. Additionally, the number of active components included in the AO systems and the complexity of their interactions will require a highly automated AO Sequencer that will work in concert with the TMT Telescope and Instrument Sequencers. In this paper, we will describe the control and software requirements for the whole AO system, and in particular for the RTC and the AO Sequencer. We will describe the challenges involved in developing these systems and will present a conceptual design

Projection neuron axon collaterals in the dorsal horn: placing a new player in spinal cord pain processing

The pain experience depends on the relay of nociceptive signals from the spinal cord dorsal horn to higher brain centres. This function is ultimately achieved by the output of a small population of highly specialised neurons called projection neurons (PNs). Like output neurons in other CNS regions, PNs are invested with a substantial axon collateral system that ramifies extensively within local circuits. These axon collaterals are widely distributed within and between spinal cord segments. Anatomical data on PN axon collaterals has existed since the time of Cajal, however, their function in spinal pain signalling remains unclear and is absent from current models of spinal pain processing. Despite these omissions, some insight on the potential role of PN axon collaterals can be drawn from axon collateral systems of principal or output neurons in other CNS regions such as the hippocampus, amygdala, olfactory cortex and ventral horn of the spinal cord. The connectivity and actions of axon collaterals in these systems have been well defined and used to confirm crucial roles in memory, fear, olfaction and movement control, respectively. We review this information here and propose a framework for characterising PN axon collateral function in the dorsal horn. We highlight that experimental approaches traditionally used to delineate axon collateral function in other CNS regions are not easily applied to PNs because of their scarcity relative to spinal interneurons, and the lack of cellular organisation in the dorsal horn. Finally, we emphasise how the rapid development of techniques such as viral expression of optogenetic or chemogenetic probes can overcome these challenges and allow characterisation of PN axon collateral function. Obtaining detailed information of this type is a necessary first step for incorporation of PN collateral system function into models of spinal sensory processing

Dicamba Retention in Commercial Sprayers Following Triple Rinse Cleanout Procedures, and Soybean Response to Contamination Concentrations

The commercial launch of dicamba‐tolerant (DT) crops has resulted in increased dicamba usage and a high number of dicamba off‐target movement complaints on sensitive soybeans (Glycine max L.). Dicamba is a synthetic auxin and low dosages as 0.028 g ae ha−1 can induce injury on sensitive soybean. Tank contamination has been identified as one of the sources for unintended sensitive crop exposure. The labels of new dicamba formulations require a triple rinse cleanout procedure following applications. Cleanout efficacy might vary based on the sprayer type and procedure followed. This study was performed to quantify dicamba retention in commercial sprayers and assess the risk for crop injury from remaining contaminants. The results indicate triple rinse with water was comparable to cleanout procedures utilizing ammonium, commercial tank cleaners, and glyphosate in rinses. Dicamba contaminants in final rinsates resulted in \u3c15% visual injury and no yield response when applied to sensitive soybeans at R1 stage. A survey of 25 agricultural sprayers demonstrated a cleanout efficacy of 99.996% by triple rinsing with water following applications of dicamba at 560 g ae ha−1, with concentrations of less than 1 ug mL−1 detected rinsates from the fourth rinse. A dose response experiment predicted dosages causing 5% visual injury and the yield losses were 0.1185 and 2.8525 g ae ha−1. However, symptomology was observed for all tested dosages, including the rate as low as 0.03 g ae ha−1. The results from this study suggest triple rinsing with sufficient amount of water (≥10% of tank volume) is adequate for the removal of dicamba residues from sprayers to avoid sensitive soybean damage. This study can provide producers with confidence in cleanout procedures following dicamba applications, and aid in minimizing risk for off‐target movement through tank contamination

Spinoparabrachial projection neurons form distinct classes in the mouse dorsal horn

Projection neurons in the spinal dorsal horn relay sensory information to higher brain centres. The activation of these populations is shaped by afferent input from the periphery, descending input from the brain, and input from local interneuron circuits. Much of our recent understanding of dorsal horn circuitry comes from studies in transgenic mice; however, information on projection neurons is still based largely on studies in monkey, cat, and rat. We used viral labelling to identify and record from mouse parabrachial nucleus (PBN) projecting neurons located in the dorsal horn of spinal cord slices. Overall, mouse lamina I spinoparabrachial projection neurons (SPBNs) exhibit many electrophysiological and morphological features that overlap with rat. Unbiased cluster analysis distinguished 4 distinct subpopulations of lamina I SPBNs, based on their electrophysiological properties that may underlie different sensory signalling features in each group. We also provide novel information on SPBNs in the deeper lamina (III-V), which have not been previously studied by patch clamp analysis. These neurons exhibited higher action potential discharge frequencies and received weaker excitatory synaptic input than lamina I SPBNs, suggesting this deeper population produces different sensory codes destined for the PBN. Mouse SPBNs from both regions (laminae I and III-V) were often seen to give off local axon collaterals, and we provide neuroanatomical evidence they contribute to excitatory input to dorsal horn circuits. These data provide novel information to implicate excitatory input from parabrachial projection neuron in dorsal horn circuit activity during processing of nociceptive information, as well as defining deep dorsal horn projection neurons that provide an alternative route by which sensory information can reach the PBN

Diversity of inhibitory and excitatory parvalbumin interneuron circuits in the dorsal horn

Parvalbumin-expressing interneurons (PVINs) in the spinal dorsal horn are found primarily in laminae II inner and III. Inhibitory PVINs (iPVINs) play an important role in segregating innocuous tactile input from pain-processing circuits through presynaptic inhibition of myelinated low-threshold mechanoreceptors and postsynaptic inhibition of distinct spinal circuits. By comparison, relatively little is known of the role of excitatory PVINs (ePVINs) in sensory processing. Here we use neuroanatomical and optogenetic approaches to show that ePVINs comprise a larger proportion of the PVIN population than previously reported, and that both ePVIN and iPVIN populations form synaptic connections amongst (and between) themselves. We find that these cells contribute to neuronal networks that influence activity within several functionally distinct circuits, and that aberrant activity of ePVINs under pathological conditions is well placed to contribute to the development of mechanical hypersensitivity

Is the Public willing to help the Nigerian Police during the Boko Haram crisis? A look at moderating factors.

This paper sought the opinion of 200 Nigerians on their willingness to cooperate with the Police during the Boko Haram crisis. Public perceptions of Police effectiveness during the crisis, residence location, gender and religious affiliation were used as moderators. Data was analysed using an explanatory factor analysis and structural equation modelling. Results indicated a strong association between perceived effectiveness and willingness to report to the Police with respondents who question the effectiveness of the Police being less likely to be willing to report criminal activity about Boko Haram. Further to this, the impact of religion on willingness to report was at least partially mediated by perceived effectiveness of the Police with the results showing that Christian respondents perceived the Police as less effective. Females and those living in the North were significantly less willing to report criminal activity to the Police The findings are then discussed in relation to the BH crises and directions for future research are given

Calretinin-expressing islet cells are a source of pre- and post-synaptic inhibition of non-peptidergic nociceptor input to the mouse spinal cord

Unmyelinated non-peptidergic nociceptors (NP afferents) arborise in lamina II of the spinal cord and receive GABAergic axoaxonic synapses, which mediate presynaptic inhibition. However, until now the source of this axoaxonic synaptic input was not known. Here we provide evidence that it originates from a population of inhibitory calretinin-expressing interneurons (iCRs), which correspond to lamina II islet cells. The NP afferents can be assigned to 3 functionally distinct classes (NP1–3). NP1 afferents have been implicated in pathological pain states, while NP2 and NP3 afferents also function as pruritoceptors. Our findings suggest that all 3 of these afferent types innervate iCRs and receive axoaxonic synapses from them, providing feedback inhibition of NP input. The iCRs also form axodendritic synapses, and their targets include cells that are themselves innervated by the NP afferents, thus allowing for feedforward inhibition. The iCRs are therefore ideally placed to control the input from non-peptidergic nociceptors and pruritoceptors to other dorsal horn neurons, and thus represent a potential therapeutic target for the treatment of chronic pain and itch

Suboptimal Activation of Antigen-Specific CD4+ Effector Cells Enables Persistence of M. tuberculosis In Vivo

Adaptive immunity to Mycobacterium tuberculosis controls progressive bacterial growth and disease but does not eradicate infection. Among CD4+ T cells in the lungs of M. tuberculosis-infected mice, we observed that few produced IFN-γ without ex vivo restimulation. Therefore, we hypothesized that one mechanism whereby M. tuberculosis avoids elimination is by limiting activation of CD4+ effector T cells at the site of infection in the lungs. To test this hypothesis, we adoptively transferred Th1-polarized CD4+ effector T cells specific for M. tuberculosis Ag85B peptide 25 (P25TCRTh1 cells), which trafficked to the lungs of infected mice and exhibited antigen-dependent IFN-γ production. During the early phase of infection, ∼10% of P25TCRTh1 cells produced IFN-γ in vivo; this declined to <1% as infection progressed to chronic phase. Bacterial downregulation of fbpB (encoding Ag85B) contributed to the decrease in effector T cell activation in the lungs, as a strain of M. tuberculosis engineered to express fbpB in the chronic phase stimulated P25TCRTh1 effector cells at higher frequencies in vivo, and this resulted in CD4+ T cell-dependent reduction of lung bacterial burdens and prolonged survival of mice. Administration of synthetic peptide 25 alone also increased activation of endogenous antigen-specific effector cells and reduced the bacterial burden in the lungs without apparent host toxicity. These results indicate that CD4+ effector T cells are activated at suboptimal frequencies in tuberculosis, and that increasing effector T cell activation in the lungs by providing one or more epitope peptides may be a successful strategy for TB therapy

Money: A Market Microstructure Approach

The current discussion about the future of the financial system draws heavily on a set of theories known as the ‘New Monetary Economics’. The New Monetary Economics predicts that deregulation and financial innovation will lead to a moneyless world. This paper uses a market microstructure approach to show that a common medium of exchange that serves as unit of account will remain a necessary instrument to reduce transaction costs. This finding is supported by empirical evidence from foreign exchange markets