Time-Dependent Performance of Buried Pipes in a Consolidating Soil Medium

Buried pipes are used for several applications, including water conveyance, highway drainage, and the transport of sewage. Throughout the years, it has become increasingly popular to use pipes made of thermoplastic materials due to ease of fabrication, resistance to chemical corrosion, light weight, and low cost. The objective of this research was to investigate the deformations of buried double-corrugated high-density polyethylene (HDPE) and solid-wall polyvinylchloride (PVC) pipes surrounded by a consolidating soil medium. The finite element method was used to calculate the pipe deflections throughout a time period of fifty years. Combined influence of creep and soil consolidation was considered in the analyses, and the results from these analyses were then compared to the deformations of pipes only influenced by the creep of the pipe material. Variables of this study included pipe diameter, height of backfill, pipe backfill material, construction methods, trench-widths, and boundary conditions.;Results show that approximately 90% of pipe deformations occurred during the first year of installation for both the creep analyses and the combined creep and consolidation analyses. However, throughout the first year, the pipe influenced by both the creep and consolidation condition deformed at a much slower rate. Pipes influenced only by the creep condition showed a slightly higher deformation than pipes influenced by both creep and consolidation. This may be due to the instantaneous loading of the pipe, when there is no consolidation. When a pipe is surrounded by a consolidating soil medium, the load on the pipe changes as the pore pressure dissipates as a function of time. Results from the analyses of the combined influence of creep and consolidation are not significantly different from those results obtained from the analyses of creep only behavior of buried HDPE and PVC pipes under the self-weight of soil

Effects of hippocampal damage on reward threshold and response rate during self-stimulation of the ventral tegmental area in the rat

The main purpose of this study was to explore the role of the hippocampus in motivated behavior. Rats with bilateral excitotoxic lesions of the hippocampus and controls were trained to lever press for electrical stimulation of the ventral tegmental area. Rate intensity functions were generated from an ascending and descending series of current intensities. Lesion-induced changes in sensitivity to reward were distinguished from enhancements in motor output by calculating reward thresholds and maximal response rates from the rate-intensity functions. Rats with hippocampal damage showed lower reward thresholds and higher maximal response rates than controls. These results provide further evidence of hippocampal modulation of the nucleus accumbens, suggesting that lesions of this structure enhance sensitivity to reward and increase motor output

The topology of connections between rat prefrontal, motor and sensory cortices

The connections of prefrontal cortex (PFC) were investigated in the rat brain to determine the order and location of input and output connections to motor and somatosensory cortex. Retrograde (100 nl Fluoro-Gold) and anterograde (100 nl Biotinylated Dextran Amines, BDA; Fluorescein and Texas Red) neuronanatomical tracers were injected into the subdivisions of the PFC (prelimbic, ventral orbital, ventrolateral orbital, dorsolateral orbital) and their projections studied. We found clear evidence for organized input projections from the motor and somatosensory cortices to the PFC, with distinct areas of motor and cingulate cortex projecting in an ordered arrangement to the subdivisions of PFC. As injection location of retrograde tracer was moved from medial to lateral in PFC, we observed an ordered arrangement of projections occurring in sensory-motor cortex. There was a significant effect of retrograde injection location on the position of labelled cells occurring in sensory-motor cortex (dorsoventral, anterior-posterior and mediolateral axes p < 0.001). The arrangement of output projections from PFC also displayed a significant ordered projection to sensory-motor cortex (dorsoventral p < 0.001, anterior-posterior p = 0.002 and mediolateral axes p < 0.001)

Dysconnection in schizophrenia: from abnormal synaptic plasticity to failures of self-monitoring

Over the last 2 decades, a large number of neurophysiological and neuroimaging studies of patients with schizophrenia have furnished in vivo evidence for dysconnectivity, ie, abnormal functional integration of brain processes. While the evidence for dysconnectivity in schizophrenia is strong, its etiology, pathophysiological mechanisms, and significance for clinical symptoms are unclear. First, dysconnectivity could result from aberrant wiring of connections during development, from aberrant synaptic plasticity, or from both. Second, it is not clear how schizophrenic symptoms can be understood mechanistically as a consequence of dysconnectivity. Third, if dysconnectivity is the primary pathophysiology, and not just an epiphenomenon, then it should provide a mechanistic explanation for known empirical facts about schizophrenia. This article addresses these 3 issues in the framework of the dysconnection hypothesis. This theory postulates that the core pathology in schizophrenia resides in aberrant N-methyl-D-aspartate receptor (NMDAR)–mediated synaptic plasticity due to abnormal regulation of NMDARs by neuromodulatory transmitters like dopamine, serotonin, or acetylcholine. We argue that this neurobiological mechanism can explain failures of self-monitoring, leading to a mechanistic explanation for first-rank symptoms as pathognomonic features of schizophrenia, and may provide a basis for future diagnostic classifications with physiologically defined patient subgroups. Finally, we test the explanatory power of our theory against a list of empirical facts about schizophrenia

Dopamine transporter (DAT1) and dopamine receptor D4 (DRD4) genotypes differentially impact on electrophysiological correlates of error processing

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Differences in anatomical connections across distinct areas in the rodent prefrontal cortex

Prefrontal cortex (PFC) network structure is implicated in a number of complex higher-order functions and with a range of neurological disorders. It is therefore vital to our understanding of PFC function to gain an understanding of its underlying anatomical connectivity. Here, we injected Fluoro-Gold and Fluoro-Ruby into the same sites throughout rat PFC. Tracer injections were applied to two coronal levels within the PFC (anterior +4.7mm to bregma and posterior +3.7mm to bregma). Within each coronal level, tracers were deposited at sites separated by approximately 1mm and located parallel to the medial and orbital surface of the cortex. We found that both Fluoro-Gold and Fluoro-Ruby injections produced prominent labelling in temporal and sensory-motor cortex. Fluoro-Gold produced retrograde labelling and Fluoro-Ruby largely produced anterograde labelling. Analysis of the location of these connections within temporal and sensory-motor cortex revealed a consistent topology (as the sequence of injections was followed mediolaterally along the orbital surface of each coronal level). At the anterior coronal level, injections produced a similar topology to that seen in central PFC in earlier studies from our laboratory (i.e. comparing equivalently located injections employing the same tracer), this was particularly prominent within temporal cortex. However, at the posterior coronal level this pattern of connections differed significantly, revealing higher levels of reciprocity, in both temporal cortex and sensory-motor cortex. Our findings indicate changes in the relative organization of connections arising from posterior in comparison to anterior regions of PFC, which may provide a basis to determine how complex processes are organized

Endogenous cholinergic inputs and local circuit mechanisms govern the phasic mesolimbic dopamine response to nicotine

Nicotine exerts its reinforcing action by stimulating nicotinic acetylcholine receptors (nAChRs) and boosting dopamine (DA) output from the ventral tegmental area (VTA). Recent data have led to a debate about the principal pathway of nicotine action: direct stimulation of the DAergic cells through nAChR activation, or disinhibition mediated through desensitization of nAChRs on GABAergic interneurons. We use a computational model of the VTA circuitry and nAChR function to shed light on this issue. Our model illustrates that the α4β2-containing nAChRs either on DA or GABA cells can mediate the acute effects of nicotine. We account for in vitro as well as in vivo data, and predict the conditions necessary for either direct stimulation or disinhibition to be at the origin of DA activity increases. We propose key experiments to disentangle the contribution of both mechanisms. We show that the rate of endogenous acetylcholine input crucially determines the evoked DA response for both mechanisms. Together our results delineate the mechanisms by which the VTA mediates the acute rewarding properties of nicotine and suggest an acetylcholine dependence hypothesis for nicotine reinforcement.Peer reviewe

Hippocampus and two way active avoidance conditioning: contrasting effects of cytotoxic lesion and temporary inactivation

Hippocampal lesions tend to facilitate two way active avoidance (2WAA) conditioning, where rats learn to cross to the opposite side of a conditioning chamber to avoid a tone-signaled footshock. This classical finding has been suggested to reflect that hippocampus-dependent place/context memory inhibits 2WAA (a crossing response to the opposite side is inhibited by the memory that this is the place where a shock was received on the previous trial). However, more recent research suggests other aspects of hippocampal function that may support 2WAA learning. More specifically, the ventral hippocampus has been shown to contribute to behavioral responses to aversive stimuli and to positively modulate the meso-accumbens dopamine system, whose activation has been implicated in 2WAA learning. Permanent hippocampal lesions may not reveal these contributions because, following complete and permanent loss of hippocampal output, other brain regions may mediate these processes or because deficits could be masked by lesion-induced extra-hippocampal changes, including an upregulation of accumbal dopamine transmission. Here, we re-examined the hippocampal role in 2WAA learning in Wistar rats, using permanent NMDA-induced neurotoxic lesions and temporary functional inhibition by muscimol or tetrodotoxin (TTX) infusion. Complete hippocampal lesions tended to facilitate 2WAA learning, whereas ventral or dorsal hippocampal lesions had no effect. In contrast, ventral or dorsal hippocampal muscimol or TTX infusions impaired 2WAA learning. Ventral infusions caused an immediate impairment, whereas after dorsal infusions rats showed intact 2WAA learning for 40-50 min, before a marked deficit emerged. These data show that functional inhibition of ventral hippocampus disrupts 2WAA learning, while the delayed impairment following dorsal infusions may reflect the time required for drug diffusion to ventral hippocampus. Overall, using temporary functional inhibition, our study shows that the ventral hippocampus contributes to 2WAA learning. Permanent lesions may not reveal these contributions due to functional compensation and extra-hippocampal lesion effects

Stress-Induced Reinstatement of Drug Seeking: 20 Years of Progress

In human addicts, drug relapse and craving are often provoked by stress. Since 1995, this clinical scenario has been studied using a rat model of stress-induced reinstatement of drug seeking. Here, we first discuss the generality of stress-induced reinstatement to different drugs of abuse, different stressors, and different behavioral procedures. We also discuss neuropharmacological mechanisms, and brain areas and circuits controlling stress-induced reinstatement of drug seeking. We conclude by discussing results from translational human laboratory studies and clinical trials that were inspired by results from rat studies on stress-induced reinstatement. Our main conclusions are (1) The phenomenon of stress-induced reinstatement, first shown with an intermittent footshock stressor in rats trained to self-administer heroin, generalizes to other abused drugs, including cocaine, methamphetamine, nicotine, and alcohol, and is also observed in the conditioned place preference model in rats and mice. This phenomenon, however, is stressor specific and not all stressors induce reinstatement of drug seeking. (2) Neuropharmacological studies indicate the involvement of corticotropin-releasing factor (CRF), noradrenaline, dopamine, glutamate, kappa/dynorphin, and several other peptide and neurotransmitter systems in stress-induced reinstatement. Neuropharmacology and circuitry studies indicate the involvement of CRF and noradrenaline transmission in bed nucleus of stria terminalis and central amygdala, and dopamine, CRF, kappa/dynorphin, and glutamate transmission in other components of the mesocorticolimbic dopamine system (ventral tegmental area, medial prefrontal cortex, orbitofrontal cortex, and nucleus accumbens). (3) Translational human laboratory studies and a recent clinical trial study show the efficacy of alpha-2 adrenoceptor agonists in decreasing stress-induced drug craving and stress-induced initial heroin lapse

Diurnal rhythms in neural activation in the mesolimbic reward system: critical role of the medial prefrontal cortex

Previous evidence suggests a circadian modulation of drug‐seeking behavior and responsiveness to drugs of abuse. To identify potential mechanisms for rhythmicity in reward, a marker of neural activation (c F os) was examined across the day in the mesolimbic reward system. Rats were perfused at six times during the day [zeitgeber times ( ZT s): 2, 6, 10, 14, 18, and 22], and brains were analysed for c F os and tyrosine hydroxylase ( TH )‐immunoreactive ( IR ) cells. Rhythmic expression of c F os was observed in the nucleus accumbens ( NA c) core and shell, in the medial prefrontal cortex (m PFC ), and in TH ‐ IR and non‐ TH ‐ IR cells in the ventral tegmental area ( VTA ), with peak expression during the late night and nadirs during the late day. No significant rhythmicity was observed in the basolateral amgydala or the dentate gyrus. As the m PFC provides excitatory input to both the NA c and VTA , this region was hypothesised to be a key mediator of rhythmic neural activation in the mesolimbic system. Hence, the effects of excitotoxic m PFC lesions on diurnal rhythms in c F os immunoreactivity at previously observed peak ( ZT 18) and nadir ( ZT 10) times were examined in the NA c and VTA . m PFC lesions encompassing the prelimbic and infralimbic subregions attenuated peak c F os immunoreactivity in the NA c, eliminating the diurnal rhythm, but had no effect on VTA rhythms. These results suggest that rhythmic neural activation in the mesolimbic system may contribute to diurnal rhythms in reward‐related behaviors, and indicate that the m PFC plays a critical role in mediating rhythmic neural activation in the NA c. Previous evidence suggests a circadian modulation of drug‐seeking behavior and responsiveness to drugs of abuse. To identify potential mechanisms for rhythmicity in reward, a maker of neural activation (c F os) was examined across the day in the mesolimbic reward system.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/99016/1/ejn12224.pd