Elevated Firing Research Articles

Experimental investigation on the fire and thermal smoke spread in tunnels: Effects of fire elevation

Previously, studies related to tunnel fires predominately concentrated on the fire at ground level while the risk of elevated fires caused by different vehicle heights was mostly ignored. In the current research, pool fires elevated at seven levels were experimentally studied in two reduced-scale model tunnels with both natural and longitudinal ventilation. Fuel burning rate, temperature profile, and thermal smoke stratification affected by the fire elevation were successively explored. Experimental results declared the major findings as 1) Fuel burning rate of the 8 cm × 8 cm pool fire was indistinctly affected by the fire elevation while it increased rapidly with the elevated height as pool size increased; 2) In the natural-ventilated tunnel, the maximum temperature significantly increased with the fire elevation and was found to be well predicted by the modified models with a linear correlation versus Q2/5Hd¯ or QD∗2/5·DfHd¯ and a constant value equal to 2.9. When longitudinal ventilation was activated, flame deflection, shortened back-layering length, and decreased maximum temperature were respectively observed. 3) Interface of the smoke-air layer was lifted, and thermal smoke stratification was promoted by the fire elevation. Good agreement was achieved between the present measurements and temperature quotient proposed by Newman. Correlation by using modified Froude number denoted different characteristics of smoke stratification of ground fire and elevated fire.

Trial-to-Trial Variability of Spiking Delay Activity in Prefrontal Cortex Constrains Burst-Coding Models of Working Memory.

A hallmark neuronal correlate of working memory (WM) is stimulus-selective spiking activity of neurons in PFC during mnemonic delays. These observations have motivated an influential computational modeling framework in which WM is supported by persistent activity. Recently, this framework has been challenged by arguments that observed persistent activity may be an artifact of trial-averaging, which potentially masks high variability of delay activity at the single-trial level. In an alternative scenario, WM delay activity could be encoded in bursts of selective neuronal firing which occur intermittently across trials. However, this alternative proposal has not been tested on single-neuron spike-train data. Here, we developed a framework for addressing this issue by characterizing the trial-to-trial variability of neuronal spiking quantified by Fano factor (FF). By building a doubly stochastic Poisson spiking model, we first demonstrated that the burst-coding proposal implies a significant increase in FF positively correlated with firing rate, and thus loss of stability across trials during the delay. Simulation of spiking cortical circuit WM models further confirmed that FF is a sensitive measure that can well dissociate distinct WM mechanisms. We then tested these predictions on datasets of single-neuron recordings from macaque PFC during three WM tasks. In sharp contrast to the burst-coding model predictions, we only found a small fraction of neurons showing increased WM-dependent burstiness, and stability across trials during delay was strengthened in empirical data. Therefore, reduced trial-to-trial variability during delay provides strong constraints on the contribution of single-neuron intermittent bursting to WM maintenance.SIGNIFICANCE STATEMENT There are diverging classes of theoretical models explaining how information is maintained in working memory by cortical circuits. In an influential model class, neurons exhibit persistent elevated memorandum-selective firing, whereas a recently developed class of burst-coding models suggests that persistent activity is an artifact of trial-averaging, and spiking is sparse in each single trial, subserved by brief intermittent bursts. However, this alternative picture has not been characterized or tested on empirical spike-train data. Here we combine mathematical analysis, computational model simulation, and experimental data analysis to test empirically these two classes of models and show that the trial-to-trial variability of empirical spike trains is not consistent with burst coding. These findings provide constraints for theoretical models of working memory.

Orbital Influence on Precipitation, Fire, and Grass Community Composition From 1.87 to 1.38 Ma in the Turkana Basin, Kenya

The Turkana Basin in northern Kenya and southern Ethiopia has yielded hundreds of hominin fossils and is among the most important localities in the world for studying human origins. High resolution climate and vegetation reconstructions from this region can elucidate potential linkages between hominin evolution and environmental change. Microcharcoal and phytoliths were examined from a 216 m (1.87–1.38 Ma) drill core (WTK13), which targeted paleo-Lake Lorenyang sediments from the Nachukui Formation of the Turkana Basin. A total of 287 samples were analyzed at ∼32–96 cm intervals, providing millennial-scale temporal resolution. To better understand how basin sediments record fire and vegetation from the watershed, the paleorecord was compared with nine modern sediment samples collected from Lake Turkana along a transect of increasing distance from the 1978 to 1979 shoreline. This included vegetation surveys and phytolith production data for species from areas proximal to the basin. We found that phytolith and microcharcoal concentrations decreased predictably moving off shore. However, phytoliths from plants sourced in the Ethiopian Highlands increased moving off shore, likely the result of increased exposure to the Omo River sediment plume. In our down-core study, microcharcoal was well-preserved but phytolith preservation was poor below ∼60 m (∼1.50 Ma). Spectral analysis revealed that microcharcoal often varied at precessional (∼21 kyr) periodicities, and through a correlation with δDwax, linked orbitally forced peaks in precipitation with elevated fire on the landscape. Phytoliths revealed that alternating mesic C4 versus xeric C4 grass dominance likely varied at precessional periodicities as well, but that grass community composition was also mediated by basin geometry. Two high eccentricity intervals of particularly high amplitude and abrupt environmental change were centered at ∼1.72 and 1.50 Ma, with the intervening period experiencing high fire variability. With the switch from lacustrine to fluvial-deltaic deposition at the core site by 1.5 Ma, mesic C4 grasses dominated and fire activity was high. This upper interval correlated to the time interval from which Nariokotome Boy (Homo erectus/ergaster) was discovered 3 km east of our drill site. Phytoliths indicated a seasonally wet and open landscape dominated by xeric C4 grasses, sedges, and other herbaceous plants.

Reduction of corpus callosum activity during whisking leads to interhemispheric decorrelation

Interhemispheric correlation between homotopic areas is a major hallmark of cortical physiology and is believed to emerge through the corpus callosum. However, how interhemispheric correlations and corpus callosum activity are affected by behavioral states remains unknown. We performed laminar extracellular and intracellular recordings simultaneously from both barrel cortices in awake mice. We find robust interhemispheric correlations of both spiking and synaptic activities that are reduced during whisking compared to quiet wakefulness. Accordingly, optogenetic inactivation of one hemisphere reveals that interhemispheric coupling occurs only during quiet wakefulness, and chemogenetic inactivation of callosal terminals reduces interhemispheric correlation especially during quiet wakefulness. Moreover, in contrast to the generally elevated firing rate observed during whisking epochs, we find a marked decrease in the activity of imaged callosal fibers. Our results indicate that the reduction in interhemispheric coupling and correlations during active behavior reflects the specific reduction in the activity of callosal neurons.

GRK3 deficiency elicits brain immune activation and psychosis

The G protein-coupled receptor kinase (GRK) family member protein GRK3 has been linked to the pathophysiology of schizophrenia and bipolar disorder. Expression, as well as protein levels, of GRK3 are reduced in post-mortem prefrontal cortex of schizophrenia subjects. Here, we investigate functional behavior and neurotransmission related to immune activation and psychosis using mice lacking functional Grk3 and utilizing a variety of methods, including behavioral, biochemical, electrophysiological, molecular, and imaging methods. Compared to wildtype controls, the Grk3−/− mice show a number of aberrations linked to psychosis, including elevated brain levels of IL-1β, increased turnover of kynurenic acid (KYNA), hyper-responsiveness to D-amphetamine, elevated spontaneous firing of midbrain dopamine neurons, and disruption in prepulse inhibition. Analyzing human genetic data, we observe a link between psychotic features in bipolar disorder, decreased GRK expression, and increased concentration of CSF KYNA. Taken together, our data suggest that Grk3−/− mice show face and construct validity relating to the psychosis phenotype with glial activation and would be suitable for translational studies of novel immunomodulatory agents in psychotic disorders.

Microstimulation-evoked neural responses in visual cortex are depth dependent

BackgroundCortical visual prostheses often use penetrating electrode arrays to deliver microstimulation to the visual cortex. To optimize electrode placement within the cortex, the neural responses to microstimulation at different cortical depths must first be understood. ObjectiveWe investigated how the neural responses evoked by microstimulation in cortex varied with cortical depth, of both stimulation and response. MethodsA 32-channel single shank electrode array was inserted into the primary visual cortex of anaesthetized rats, such that it spanned all cortical layers. Microstimulation with currents up to 14 μA (single biphasic pulse, 200 μs per phase) was applied at depths spanning 1600 μm, while simultaneously recording neural activity on all channels within a response window 2.25–11 ms. ResultsStimulation elicited elevated neuronal firing rates at all depths of cortex. Compared to deep sites, superficial stimulation sites responded with higher firing rates at a given current and had lower thresholds. The laminar spread of evoked activity across cortical depth depended on stimulation depth, in line with anatomical models. ConclusionStimulation in the superficial layers of visual cortex evokes local neural activity with the lowest thresholds, and stimulation in the deep layers evoked the most activity across the cortical column. In conjunction with perceptual reports, these data suggest that the optimal electrode placement for cortical microstimulation prostheses has electrodes positioned in layers 2/3, and at the top of layer 5.

The Effect of Antecedent Fire Severity on Reburn Severity and Fuel Structure in a Resprouting Eucalypt Forest in Victoria, Australia

Research highlights—Feedbacks between fire severity, vegetation structure and ecosystem flammability are understudied in highly fire-tolerant forests that are dominated by epicormic resprouters. We examined the relationships between the severity of two overlapping fires in a resprouting eucalypt forest and the subsequent effect of fire severity on fuel structure. We found that the likelihood of a canopy fire was the highest in areas that had previously been exposed to a high level of canopy scorch or consumption. Fuel structure was sensitive to the time since the previous canopy fire, but not the number of canopy fires. Background and Objectives—Feedbacks between fire and vegetation may constrain or amplify the effect of climate change on future wildfire behaviour. Such feedbacks have been poorly studied in forests dominated by highly fire-tolerant epicormic resprouters. Here, we conducted a case study based on two overlapping fires within a eucalypt forest that was dominated by epicormic resprouters to examine (1) whether past wildfire severity affects future wildfire severity, and (2) how combinations of understorey fire and canopy fire within reburnt areas affect fuel properties. Materials and Methods—The study focused on ≈77,000 ha of forest in south-eastern Australia that was burnt by a wildfire in 2007 and reburnt in 2013. The study system was dominated by eucalyptus trees that can resprout epicormically following fires that substantially scorch or consume foliage in the canopy layer. We used satellite-derived mapping to assess whether the severity of the 2013 fire was affected by the severity of the 2007 fire. Five levels of fire severity were considered (lowest to highest): unburnt, low canopy scorch, moderate canopy scorch, high canopy scorch and canopy consumption. Field surveys were then used to assess whether combinations of understorey fire (<80% canopy scorch) and canopy fire (>90% canopy consumption) recorded over the 2007 and 2013 fires caused differences in fuel structure. Results—Reburn severity was influenced by antecedent fire severity under severe fire weather, with the likelihood of canopy-consuming fire increasing with increasing antecedent fire severity up to those classes causing a high degree of canopy disturbance (i.e., high canopy scorch or canopy consumption). The increased occurrence of canopy-consuming fire largely came at the expense of the moderate and high canopy scorch classes, suggesting that there was a shift from crown scorch to crown consumption. Antecedent fire severity had little effect on the severity patterns of the 2013 fire under nonsevere fire weather. Areas affected by canopy fire in 2007 and/or 2013 had greater vertical connectivity of fuels than sites that were reburnt by understorey fires, though we found no evidence that repeated canopy fires were having compounding effects on fuel structure. Conclusions—Our case study suggests that exposure to canopy-defoliating fires has the potential to increase the severity of subsequent fires in resprouting eucalypt forests in the short term. We propose that the increased vertical connectivity of fuels caused by resprouting and seedling recruitment were responsible for the elevated fire severity. The effect of antecedent fire severity on reburn severity will likely be constrained by a range of factors, such as fire weather.

MYBL2 and ATM suppress replication stress in pluripotent stem cells.

Replication stress, a major cause of genome instability in cycling cells, is mainly prevented by the ATR‐dependent replication stress response pathway in somatic cells. However, the replication stress response pathway in embryonic stem cells (ESCs) may be different due to alterations in cell cycle phase length. The transcription factor MYBL2, which is implicated in cell cycle regulation, is expressed a hundred to a thousand‐fold more in ESCs compared with somatic cells. Here we show that MYBL2 activates ATM and suppresses replication stress in ESCs. Consequently, loss of MYBL2 or inhibition of ATM or Mre11 in ESCs results in replication fork slowing, increased fork stalling and elevated origin firing. Additionally, we demonstrate that inhibition of CDC7 activity rescues replication stress induced by MYBL2 loss and ATM inhibition, suggesting that uncontrolled new origin firing may underlie the replication stress phenotype resulting from loss/inhibition of MYBL2 and ATM. Overall, our study proposes that in addition to ATR, a MYBL2‐MRN‐ATM replication stress response pathway functions in ESCs to control DNA replication initiation and prevent genome instability.

Deletion of BDNF in Pax2 Lineage-Derived Interneuron Precursors in the Hindbrain Hampers the Proportion of Excitation/Inhibition, Learning, and Behavior

Numerous studies indicate that deficits in the proper integration or migration of specific GABAergic precursor cells from the subpallium to the cortex can lead to severe cognitive dysfunctions and neurodevelopmental pathogenesis linked to intellectual disabilities. A different set of GABAergic precursors cells that express Pax2 migrate to hindbrain regions, targeting, for example auditory or somatosensory brainstem regions. We demonstrate that the absence of BDNF in Pax2-lineage descendants of BdnfPax2KOs causes severe cognitive disabilities. In BdnfPax2KOs, a normal number of parvalbumin-positive interneurons (PV-INs) was found in the auditory cortex (AC) and hippocampal regions, which went hand in hand with reduced PV-labeling in neuropil domains and elevated activity-regulated cytoskeleton-associated protein (Arc/Arg3.1; here: Arc) levels in pyramidal neurons in these same regions. This immaturity in the inhibitory/excitatory balance of the AC and hippocampus was accompanied by elevated LTP, reduced (sound-induced) LTP/LTD adjustment, impaired learning, elevated anxiety, and deficits in social behavior, overall representing an autistic-like phenotype. Reduced tonic inhibitory strength and elevated spontaneous firing rates in dorsal cochlear nucleus (DCN) brainstem neurons in otherwise nearly normal hearing BdnfPax2KOs suggests that diminished fine-grained auditory-specific brainstem activity has hampered activity-driven integration of inhibitory networks of the AC in functional (hippocampal) circuits. This leads to an inability to scale hippocampal post-synapses during LTP/LTD plasticity. BDNF in Pax2-lineage descendants in lower brain regions should thus be considered as a novel candidate for contributing to the development of brain disorders, including autism.

BNSTAV GABA-PVNCRF Circuit Regulates Visceral Hypersensitivity Induced by Maternal Separation in Vgat-Cre Mice.

Visceral hypersensitivity as a common clinical manifestation of irritable bowel syndrome (IBS) may contribute to the development of chronic visceral pain. Our prior studies authenticated that the activation of the corticotropin-releasing factor (CRF) neurons in paraventricular nucleus (PVN) contributed to visceral hypersensitivity in mice, but puzzles still remain with respect to the underlying hyperactivation of corticotropin-releasing factor neurons. Herein, we employed maternal separation (MS) to establish mouse model of visceral hypersensitivity. The neuronal circuits associated with nociceptive hypersensitivity involved paraventricular nucleus CRF neurons by means of techniques such as behavioral test, pharmacology, molecular biology, retrograde neuronal circuit tracers, electrophysiology, chemogenetics and optogenetics. MS could predispose the elevated firing frequency of CRF neurons in PVN in murine adulthood, which could be annulled via the injection of exogenous GABA (0.3mM, 0.2µl) into PVN. The PVN-projecting GABAergic neurons were mainly distributed in the anterior ventral (AV) region in the bed nucleus of stria terminalis (BNST), wherein the excitability of these GABAergic neurons was reduced. Casp3 virus was utilized to induce apoptosis of GABA neurons in BNST-AV region, resulting in the activation of CRF neurons in PVN and visceral hyperalgesia. In parallel, chemogenetic and optogenetic approaches to activate GABAergic BNSTAV-PVN circuit in MS mice abated the spontaneous firing frequency of PVN CRF neurons and prevented the development of visceral hypersensitivity. A priori, PVNCRF-projecting GABAergic neurons in BNST-AV region participated in the occurrence of visceral hypersensitivity induced by MS. Our research may provide a new insight into the neural circuit mechanism of chronic visceral pain.

Phasic Neuronal Firing in the Rodent Nucleus of the Solitary Tract ex vivo.

Phasic pattern of neuronal activity has been previously described in detail for magnocellular vasopressin neurons in the hypothalamic paraventricular and supraoptic nuclei. This characteristic bistable pattern consists of alternating periods of electrical silence and elevated neuronal firing, implicated in neuropeptide release. Here, with the use of multi-electrode array recordings ex vivo, we aimed to study the firing pattern of neurons in the nucleus of the solitary tract (NTS) – the brainstem hub for homeostatic, cardio-vascular, and metabolic processes. Our recordings from the mouse and rat hindbrain slices reveal the phasic activity pattern to be displayed by a subset of neurons in the dorsomedial NTS subjacent to the area postrema (AP), with the inter-spike interval distribution closely resembling that reported for phasic magnocellular vasopressin cells. Additionally, we provide interspecies comparison, showing higher phasic frequency and firing rate of phasic NTS cells in mice compared to rats. Further, we describe daily changes in their firing rate and pattern, peaking at the middle of the night. Last, we reveal these phasic cells to be sensitive to α2 adrenergic receptors activation and to respond to electrical stimulation of the AP. This study provides a comprehensive description of the phasic neuronal activity in the rodent NTS and identifies it as a potential downstream target of the AP noradrenergic system.

Reduced Pressure Effect On The Flame Length Of Elevated N-Heptane Fires In An Aircraft Cargo Compartment

ABSTRACT This paper investigates the influence of reduced pressure on flame characteristics of elevated n-heptane fires in an aircraft cargo compartment, including the flame height driven by the weak plume and flame extension length driven by the strong plume, in order to provide theoretical support to the fire detection and surface material design. A series of elevated n-heptane pool fire experiments were carried out in a full-size simulated aircraft cargo compartment at different atmospheric pressures (70 kPa, 80 kPa, 90 kPa, 100 kPa). Results show that the experimental data of flame height and flame extension length at normal pressure agree well with Heskestad and Quintiere & Grove models, however, which cannot predict these flame characteristics of elevated fires. As the fire source elevates gradually, the flame height and flame extension length increase. Then modified flame height and flame extension length models at normal pressure were established by considering the elevated height effect. Furthermore, due to reduced pressure effect on the air entrainment into the fire plume, the flame height and flame extension length increase with the decreasing pressure. New flame height and flame extension length correlations applicable to the reduced pressure conditions were proposed by introducing a reduced pressure coefficient and modified nondimensional heat release rates.

Predisposition of Neonatal Maternal Separation to Visceral Hypersensitivity via Downregulation of Small-Conductance Calcium-Activated Potassium Channel Subtype 2 (SK2) in Mice.

Background Visceral hypersensitivity is a common occurrence of gastrointestinal diseases such as irritable bowel syndrome (IBS), wherein early-life stress (ELS) may have a high predisposition to the development of visceral hypersensitivity in adulthood, with the specific underlying mechanism still elusive. Herein, we assessed the potential effect of small-conductance calcium-activated potassium channel subtype 2 (SK2) in the spinal dorsal horn (DH) on the pathogenesis of visceral hypersensitivity induced by maternal separation (MS) in mice. Methods Neonatal mice were subjected to the MS paradigm, an established ELS model. In adulthood, the visceral pain threshold and the abdominal withdrawal reflex (AWR) were measured with an inflatable balloon. The elevated plus maze, open field test, sucrose preference test, and forced swim test were employed to evaluate the anxiety- and depression-like behaviors. The expression levels of SK2 in the spinal DH were determined by immunofluorescence and western blotting. The mRNA of SK2 and membrane palmitoylated protein 2 (MPP2) were determined by quantitative real-time polymerase chain reaction (qRT-PCR). Electrophysiology was applied to evaluate the neuronal firing rates and SK2 channel-mediated afterhyperpolarization current (IAHP). The interaction between MPP2 and SK2 was validated by coimmunoprecipitation. Results In contrast to the naïve mice, ethological findings in MS mice revealed lowered visceral pain threshold, more evident anxiety- and depression-like behaviors, and downregulated expression of membrane SK2 protein and MPP2 protein. Moreover, electrophysiological results indicated increased neuronal firing rates and decreased IAHP in the spinal DH neurons. Nonetheless, intrathecal injection of the SK2 channel activator 1-ethyl-2-benzimidazolinone (1-EBIO) in MS mice could reverse the electrophysiological alterations and elevate the visceral pain threshold. In the naïve mice, administration of the SK2 channel blocker apamin abated IAHP and elevated spontaneous neuronal firing rates in the spinal DH neurons, reducing the visceral pain threshold. Finally, disruption of the MPP2 expression by small interfering RNA (siRNA) could amplify visceral hypersensitivity in naïve mice. Conclusions ELS-induced visceral pain and visceral hypersensitivity are associated with the underfunction of SK2 channels in the spinal DH.

Synaptic and intrinsic mechanisms underlying development of cortical direction selectivity.

Modifications of synaptic inputs and cell-intrinsic properties both contribute to neuronal plasticity and development. To better understand these mechanisms, we undertook an intracellular analysis of the development of direction selectivity in the ferret visual cortex, which occurs rapidly over a few days after eye opening. We found strong evidence of developmental changes in linear spatiotemporal receptive fields of simple cells, implying alterations in circuit inputs. Further, this receptive field plasticity was accompanied by increases in near-spike-threshold excitability and input-output gain that resulted in dramatically increased spiking responses in the experienced state. Increases in subthreshold membrane responses induced by the receptive field plasticity and the increased input-output spiking gain were both necessary to explain the elevated firing rates in experienced ferrets. These results demonstrate that cortical direction selectivity develops through a combination of plasticity in inputs and in cell-intrinsic properties.

Effects of elevated pool fire in a naturally ventilated compartment

This paper presents an experimental analysis of fire behavior due to elevated fuel pan with diesel in a fixed ventilated compartment of size 4 m (height) × 4 m (length) × 4 m (width) having door opening of 2 m (Hd) × 1 m (W). A reasonably large pool size of diameter 0.8 m is used in experiments so that the results may be useful for industrial fire hazard analysis. The variable parameter, taken as fire source height ‘h’ is from the floor that is 0.3 m, 0.6 m, 0.9 m, 1.2 m, 1.5 m and 1.8 m. During experimentation, it is observed that variation in pan height significantly affects the mass loss rate (MLR), heat release rate (HRR), flame behavior, smoke layer height, doorway mass flow and global equivalence ratio (GER). In case of higher elevated fire, HRR decreased drastically, one-fourth of maximum HRR value obtained in case of lower elevation of fire source. Lowest elevated pool fire shows good agreement for MLR and HRR with other experiment performed in an open space, i.e., well ventilated condition. For a significant elevated fire, the average fuel mass loss rate, flame temperature, smoke layer height, doorway mass flow rate and exit velocity were lower. With respect to above parameters, fire scenario inside the compartment seems to be less hazardous in case of higher elevated fire. A completely different trend has been found for the variation of GER with respect to MLR in current study.

Disinhibition of PVN-projecting GABAergic neurons in AV region in BNST participates in visceral hypersensitivity in rats

Ample evidence suggests that early life stress (ELS) is a high-risk factor for the development of visceral pain disorders, whereas the mechanism underlying neuronal circuit remains elusive. Herein, we employed neonatal colorectal distension (CRD) to induce visceral hypersensitivity in rats. A combination of electrophysiology, pharmacology, behavioral test, molecular biology, chemogenetics and optogenetics confirmed that CRD in neonatal rats could predispose the elevated firing frequency of the parvocellular corticotropin-releasing hormone (CRH) neurons in the paraventricular nucleus of hypothalamus (PVN) in adulthood, with the CRH neurons activated and the frequency of spontaneous inhibitory postsynaptic currents (sIPSC) diminished, both contributing to chronic visceral hypersensitivity. Moreover, following administration of exogenous GABA (300 mM/0.5 μL) and GABAA receptor agonist muscimol (3 mM/0.5 μL) in PVN, visceral hyperalgesia was abrogated. In addition, the PVN-projecting GABAergic neurons were mainly distributed in the anterior ventral (AV) region in the bed nucleus of stria terminalis (BNST), and the excitability of these GABAergic neurons was weakened in visceral hypersensitivity. Specific depletion of the GABAergic neurons in AV region precipitated visceral hyperalgesia. Moreover, chemogenetic activation of the PVN-projecting neurons alleviated the visceral hypersensitivity. Photoactivation of PVN-projecting GABAergic neurons abated the visceral hypersensitivity in neonatal-CRD rats, whereas photoinhibition evoked visceral hyperalgesia in naïve rats. Our findings demonstrated that disinhibition of the PVN-projecting GABAergic neurons in AV region contributed to the excitation of CRH neurons, thereby mediating visceral hypersensitivity. Our study might provide a novel insight into the neuronal circuits involved in the ELS-induced visceral hypersensitivity.

Hypothalamic Regulation of Blood Pressure

In addition to brainstem nuclei well‐known to be involved in baroreflex regulation of blood pressure, several hypothalamic regions have also been shown to modulate autonomic regulation and cardiovascular function. Among them, the paraventricular nucleus (PVN) comprised of magnocellular neurons involved in vasopressin and oxytocin secretion and parvocellular neurons involved in pre‐sympathetic activity. Elevated firing activity of pre‐sympathetic PVN neurons is thought to contribute to hypertension. The PVN also contains components of the renin‐angiotensin system (RAS), like the angiotensin‐II type 1 receptor (AT1R) which expression is enhanced in hypertensive conditions. We previously reported that Angiotensin converting enzyme 2 (ACE2) is also expressed in the PVN and capable of metabolizing Ang‐II levels thus reducing Ang‐II pro‐hypertensive signaling. More recently, we identified ADAM17 as a critical mediator of AT1R downstream signaling, supporting the maintenance of hypertension and neuro‐inflammation. We observed that during RAS overactivity, AT1R stimulation leads to translocation of ADAM17 from the cytoplasm to the plasma membrane, leading to enhanced activity of this sheddase. As a result, ACE2 is cleaved by ADAM17 from the plasma membrane and the compensatory activity of the enzyme is thus compromised, promoting an imbalance of autonomic function and favoring the development of neurogenic hypertension. Recently, we investigated the interaction of AT1R, ADAM17 and ACE2 on PVN pre‐sympathetic neurons and hypothesized that ADAM17 would impair ACE2 regulation of neuronal activity on these cells, leading to an increase in sympathetic outflow and eventually blood pressure. We also attempted to identify patterns of expression for these RAS components on specific PVN neurons. To address these questions, we relied on novel transgenic mouse models with selective deletion of RAS components in the PVN and electrophysiology. Our observations suggest that ACE2 maintains inhibitory neurotransmission into the PVN and its expression is prevalent on inhibitory neurons. On the other hand, ADAM17 is critical for Ang II‐mediated activation of kidney‐related presympathetic glutamatergic neurons in the PVN, confirming the supportive role of ADAM17 in increasing presympathetic neuronal activity. Balancing inhibitory and excitatory neurotransmission from the PVN is essential to prevent a sympathetic overdrive and our observations provide new targets to modulate excessive sympathetic activity in hypertension.Support or Funding InformationNHLBI HL093178.

A Review on Numerical Analysis of RC Flat Slabs Exposed to Fire

This paper aims at presenting and discussing the numerical studies performed to estimate the mechanical and thermal behavior of RC flat slabs at elevated temperature and fire. The numerical analysis is carried out using finite element programs by developing models to simulate the performance of the buildings subjected to fire. The mechanical and thermal properties of the materials obtained from the experimental work are involved in the modeling that the outcomes will be more realistic. Many parameters related to fire resistance of the flat slabs have been studied and the finite element analysis results reveal that the width and thickness of the slab, the temperature gradient, the fire direction, the exposure duration and the thermal restraint are important factors that influence the vertical deflection, bending moment and force membrane of the flat slabs exposed to fire. However, the validation of the models is verified by comparing their results to the available experimental date. The finite element modeling contributes in saving cost and time consumed by experiments.

Unexpected Rule-Changes in a Working Memory Task Shape the Firing of Histologically Identified Delay-Tuned Neurons in the Prefrontal Cortex

Working memory-guided behaviors require memory retention during delay periods, when subsets of prefrontal neurons have been reported to exhibit persistently elevated firing. What happens to delay activity when information stored in working memory is no longer relevant for guiding behavior? In this study, we perform juxtacellular recording and labeling of delay-tuned (-elevated or -suppressed) neurons in the prelimbic cortex of freely moving rats, performing a familiar delayed cue-matching-to-place task. Unexpectedly, novel task-rules are introduced, rendering information held in working memory irrelevant. Following successful strategy switching within one session, delay-tuned neurons are filled with neurobiotin for histological analysis. Delay-elevated neurons include pyramidal cells with large heterogeneity of soma-dendritic distribution, molecular expression profiles, and task-relevant activity. Rule change induces heterogenous adjustments on individual neurons and ensembles' activity but cumulates in balanced firing rate reorganizations across cortical layers. Our results demonstrate divergent cellular and network dynamics when an abrupt change in task rules interferes with working memory.

Conservation implications of limited Native American impacts in pre-contact New England

An increasingly accepted paradigm in conservation attributes valued modern ecological conditions to past human activities. Disturbances, including prescribed fire, are therefore used by land managers to impede forest development in many potentially wooded landscapes under the interpretation that openland habitats were created and sustained by human-set fire for millennia. We test this paradigm using palaeoenvironmental and archaeological data from New England. Despite the region’s dense population, anthropogenic impacts on the landscape before European contact were limited, and fire activity was independent of changes in human populations. Whereas human populations reached maxima during the Late Archaic (5,000–3,000 yr bp) and Middle–Late Woodland (1,500–500 yr bp) periods, lake-sediment charcoal records indicate elevated fire activity only during the dry early Holocene (10,000–8,000 yr bp) and after European colonization. Pollen data indicate closed forests from 8,000 yr bp to the onset of European deforestation, and archaeological evidence of pre-contact horticultural activity is sparse. Climate largely controlled fire severity in New England during the postglacial interval, and widespread openlands developed only after deforestation for European agriculture. Land managers seeking to emulate pre-contact conditions should de-emphasize human disturbance and focus on developing mature forests; those seeking to maintain openlands should apply the agricultural approaches that initiated them four centuries ago. Modern land management often assumes that past human activity shaped iconic landscapes. This study finds that climate, rather than indigenous activity, controlled fire severity in New England, with open landscapes developing after deforestation for European agriculture.